Worldwide Trends in Diabetes Since 1980

1. PLoS One. 2018 May 16;13(5):e0195543. doi: 10.1371/journal.pone.0195543.
eCollection 2018.
12-year trends in cardiovascular risk factors (2002-2005 through 2011-2014) in
patients with cardiovascular diseases: Tehran lipid and glucose study.
Rabani S(1), Sardarinia M(1), Akbarpour S(1)(2), Azizi F(3), Khalili D(1),
Hadaegh F(1).
Author information:
(1)Prevention of Metabolic Disorders Research Center, Research Institute for
Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
(2)Department of Epidemiology and Biostatistics, School of Public Health, Tehran
University of Medical Sciences, Tehran, Iran.
(3)Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid
Beheshti University of Medical Sciences, Tehran, Iran.
BACKGROUND: To examine the trend of cardiovascular diseases (CVD) risk factors
among a Middle Eastern population with prevalent CVD during a median follow up of
12 years.
METHODS: Patients with prevalent CVD (n = 282, men = 167), with a mean age of
60.76 years were evaluated in four study phases of the TLGS (Tehran lipid glucose
study), 2002-2005, 2005-2008, 2008-2011, and 2011-2014. Trends of CVD risk
factors were estimated using generalized estimation equation (GEE) models, by
adjusting for gender, age and propensity scores.
RESULT: The adjusted prevalence of general and central adiposity, diabetes and
physical inactivity at baseline was 25.18, 60.14, 25.03 and 43.74%, respectively
and had increasing trends during the study period, reaching 41.32, 66.74, 43.20
and 50.32%, respectively, at the last visit. Although systolic, but not diastolic
blood pressure, decreased from 134.88 to 129.86 mmHg, the prevalence of

hypertension did not decrease (64.21% vs 68%, p value = 0.326). The prevalence of
low high density lipoprotein cholesterol (HDL-C), hypertriglyceridemia and high
non-HDL-C at baseline was 74.54, 59.89 and 96.53%, respectively, and showed
improved trends reaching 44.87, 47.12 and 96.06% respectively; however, the
favorable trend was not observed for high low density cholesterol. Significant
increasing trends were observed in the consumption of anti-hypertensive, lipid
and glucose lowering medications, but not for aspirin. The prevalence of current
smoking (11.05 vs 16.83%, p value = 0.042) and chronic kidney disease (44.16 vs
51.65%, p value = 0.054) increased during follow up.
CONCLUSION: Except for lipid profile status, dangerous trends for other CVD risk
factors were demonstrated among CVD patients, which can be a harbinger for high
rates of CVD mortality; these findings highlight the need for urgent
implementation of multicomponent interventions to control CVD risk factors among
these patients.
DOI: 10.1371/journal.pone.0195543
PMCID: PMC5955533
PMID: 29768511 [Indexed for MEDLINE]
2. J Endocr Soc. 2017 Jun 5;1(7):965-979. doi: 10.1210/js.2016-1073. eCollection
2017 Jul 1.
17β-Estradiol Promotes Islet Cell Proliferation in a Partial Pancreatectomy Mouse
Model.
Wu T(1)(2), Xu J(1)(2), Xu S(2), Wu L(2), Zhu Y(2), Li G(1)(2), Ren Z(1)(2)(3).
Author information:
(1)Department of Neurobiology, School of Basic Medicine, Anhui Medical
University, Hefei, Anhui 230032, China.

(2)Department of Anatomy, School of Basic Medicine, Anhui Medical University,
Hefei, Anhui 230032, China.
(3)Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing
100053, China.
17β-Estradiol (E2) is a multifunctional steroid hormone in modulating metabolism
in vivo. Previous studies have reported that E2 could promote insulin secretion
and protect β cells from apoptosis. In this study, the partial pancreatectomy
(PPx) model was used to study the role of E2 in islet cell proliferation. The
animals were divided into four groups, including sham control, PPx model, E2, and
E2 plus estrogen antagonist (E2 plus ICI) groups. In the E2 group,
5-bromo-2'-deoxyuridine- and Ki67-positive cells significantly increased after
PPx, and the protein expression of forkhead transcription factor M1, cyclin A2,
cyclin B1, and cyclin E2 also significantly increased in the isolated islets. The
messenger RNA expression of cyclin A2 and cyclin B2 increased in E2 treatment
group. Additionally, the effects of E2 on the PPx mice were partially blocked by
estrogen antagonist ICI182,780. The results indicated that E2 significantly
promoted islet cell proliferation in PPx model mice, and it upregulated the
expression of cell cycle genes. In conclusion, E2 treatment is beneficial for
islet cell proliferation in adult mice after PPx. A partial pancreatectomy in
mice may be an attractive model for the study of islet cell proliferation.
DOI: 10.1210/js.2016-1073
PMCID: PMC5686603
PMID: 29264547
3. Cardiovasc Diabetol. 2018 Jun 26;17(1):93. doi: 10.1186/s12933-018-0734-8.
Abdominal subcutaneous adipose tissue: a favorable adipose depot for diabetes?

Chen P(1)(2)(3)(4), Hou X(1)(2)(3)(5), Hu G(5), Wei L(1)(2)(3)(4), Jiao L(6),
Wang H(6), Chen S(1)(2)(3)(4), Wu J(1)(2)(3)(4), Bao Y(1)(2)(3)(4), Jia
W(7)(8)(9)(10).
Author information:
(1)Department of Endocrinology and Metabolism, Shanghai Jiao Tong University
Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
(2)Shanghai Diabetes Institute, Shanghai, China.
(3)Shanghai Clinical Center for Diabetes, Shanghai, China.
(4)Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
(5)Pennington Biomedical Research Center, Baton Rouge, LA, USA.
(6)Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth
People's Hospital, Shanghai, China.
(7)Department of Endocrinology and Metabolism, Shanghai Jiao Tong University
Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
wpjia@sjtu.edu.cn.
(8)Shanghai Diabetes Institute, Shanghai, China. wpjia@sjtu.edu.cn.
(9)Shanghai Clinical Center for Diabetes, Shanghai, China. wpjia@sjtu.edu.cn.
wpjia@sjtu.edu.cn.
BACKGROUND: Previous studies have documented that visceral adipose tissue is
positively associated with the risk of diabetes. However, the association of
subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to
assess the associations between different adipose distributions and the risk of
newly diagnosed diabetes in Chinese adults.
METHODS: The Shanghai Nicheng Cohort Study was conducted among Chinese adults
aged 45-70 years. The baseline data of 12,137 participants were analyzed.
Subcutaneous and visceral fat area (SFA and VFA) were measured by magnetic
resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose
tolerance test.
RESULTS: The multivariable-adjusted odds ratios (OR) and 95% confidence intervals
(CI) of newly diagnosed diabetes per 1-standard deviation increase in SFA and VFA
were 1.29 (1.19-1.39) and 1.61 (1.49-1.74) in men, and 1.10 (1.03-1.18) and 1.56
(1.45-1.67) in women, respectively. However, the association between SFA and
newly diagnosed diabetes disappeared in men and was reversed in women (OR 0.86
[95% CI, 0.78-0.94]) after additional adjustment for body mass index (BMI) and
VFA. The positive association between VFA and newly diagnosed diabetes remained
significant in both sexes after further adjustment for BMI and SFA. Areas under
the receiver operating characteristic curve of newly diagnosed diabetes predicted
by VFA (0.679 [95% CI, 0.659-0.699] for men and 0.707 [95% CI, 0.690-0.723] for
women) were significantly larger than by the other adiposity indicators.
CONCLUSIONS: SFA was beneficial for lower risk of newly diagnosed diabetes in
women but was not associated with newly diagnosed diabetes in men after taking
general obesity and visceral obesity into account. VFA, however, was associated
with likelihood of newly diagnosed diabetes in both Chinese men and women.
DOI: 10.1186/s12933-018-0734-8
PMCID: PMC6020307
PMID: 29945626
4. Eye (Lond). 2017 May;31(S1):S1-S20. doi: 10.1038/eye.2017.53.
Action on diabetic macular oedema: achieving optimal patient management in
treating visual impairment due to diabetic eye disease.
Gale R(1)(2), Scanlon PH(1)(3), Evans M(1)(4), Ghanchi F(1)(5), Yang Y(1)(6),
Silvestri G(1)(7), Freeman M(1)(8), Maisey A(1)(9), Napier J(1)(10).
Author information:
(1)The Action on DMO group, UK.

(2)The York Hospital, York, UK.
(3)Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
(4)University Hospital, Llandough, Cardiff, UK.
(5)Bradford Teaching Hospitals, Bradford, UK.
(6)The Royal Wolverhampton NHS Trust, Wolverhampton, UK.
(7)Belfast Health & Social Care Trust, Belfast, UK.
(8)Royal Hallamshire Hospital, Sheffield, UK.
(9)Cardiff and Vale University Health Board, University Hospital of Wales,
Cardiff, UK.
(10)Bayer, Reading, UK.
This paper identifies best practice recommendations for managing diabetes and
sight-threatening diabetic eye disease. The authors provide an update for
ophthalmologists and allied healthcare professionals on key aspects of diabetes
management, supported by a review of the pertinent literature, and recommend
practice principles for optimal patient management in treating visual impairment
due to diabetic eye disease. In people with diabetes, early optimal glycaemic
control reduces the long-term risk of both microvascular and macrovascular
complications. The authors propose more can and should be done to maximise
metabolic control, promote appropriate behavioural modifications and encourage
timely treatment intensification when indicated to ameliorate diabetes-related
complications. All people with diabetes should be screened for sight-threatening
diabetic retinopathy promptly and regularly. It is shown that attitudes towards
treatment adherence in diabetic macular oedema appear to mirror patients' views
and health behaviours towards the management of their own diabetes. Awareness of
diabetic macular oedema remains low among people with diabetes, who need access
to education early in their disease about how to manage their diabetes to delay
progression and possibly avoid eye-related complications. Ophthalmologists and
allied healthcare professionals play a vital role in multidisciplinary diabetes
management and establishment of dedicated diabetic macular oedema clinics is
proposed. A broader understanding of the role of the diabetes specialist nurse

may strengthen the case for comprehensive integrated care in ophthalmic practice.
The recommendations are based on round table presentations and discussions held
in London, UK, September 2016.
DOI: 10.1038/eye.2017.53
PMCID: PMC5437340
5. Sci Rep. 2018 Apr 3;8(1):5512. doi: 10.1038/s41598-018-23812-6.
Addressing the impact of urban exposure on the incidence of type 2 diabetes
mellitus: The PERU MIGRANT Study.
Ruiz-Alejos A(1), Carrillo-Larco RM(1), Miranda JJ(1)(2), Anderson CAM(3), Gilman
RH(1)(4), Smeeth L(5), Bernabé-Ortiz A(6)(7).
Author information:
(1)CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana
Cayetano Heredia, Lima, Peru.
(2)Department of Medicine, School of Medicine, Universidad Peruana Cayetano
Heredia, Lima, Peru.
(3)Department of Family Medicine and Public Health, School of Medicine,
University of California San Diego. La Jolla, California, USA.
(4)Department of International Health, Bloomberg School of Public Health, Johns
Hopkins University, Baltimore, USA.
(5)Faculty of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, London, United Kingdom.
Cayetano Heredia, Lima, Peru. Antonio.Bernabe@upch.pe.

Tropical Medicine, London, United Kingdom. Antonio.Bernabe@upch.pe.
The aim of this study was to estimate the incidence of T2DM in three population
groups: rural, rural-to-urban migrants and urban dwellers. Data from the PERU
MIGRANT Study was analysed. The baseline assessment was conducted in 2007-2008
using a single-stage random sample and further follow-up was undertaken in
2015-16. T2DM was defined based on fasting glucose and self-reported diagnosis.
Poisson regression models and robust variance to account for cluster effects were
used for reporting risk ratios (RR) and 95%CI. At baseline, T2DM prevalence was
8% in urban, 3.6% in rural-to-urban migrants and 1.5% in rural dwellers. After
7.7 (SD: 1.1) years, 6,076 person-years of follow-up, 61 new cases were
identified. The incidence rates in the urban, migrant and rural groups were 1.6,
0.9 and 0.5 per 100 person-years, respectively. Relative to rural dwellers, a
4.3-fold higher risk (95%CI: 1.6-11.9) for developing T2DM was found in urban
dwellers and 2.7-fold higher (95%CI: 1.1-6.8) in migrants with ≥30 years of urban
exposure. Migration and urban exposure were found as significant risk factors for
developing T2DM. Within-country migration is a sociodemographic phenomenon
occurring worldwide; thus, it is necessary to disentangle the effect of urban
exposure on non-healthy habits and T2DM development.
DOI: 10.1038/s41598-018-23812-6
PMCID: PMC5883030
PMID: 29615740
6. Int J Epidemiol. 2017 Oct 1;46(5):1410-1420. doi: 10.1093/ije/dyx074.
Adherence to a healthy lifestyle and the risk of type 2 diabetes in Chinese
adults.
Lv J(1)(2), Yu C(1), Guo Y(3), Bian Z(3), Yang L(4), Chen Y(4), Hu X(5), Hou
W(6), Chen J(7), Chen Z(4), Qi L(8)(9), Li L(1)(3); China Kadoorie Biobank
Collaborative Group.
Author information:
(1)Department of Epidemiology and Biostatistics, School of Public Health, Peking
University Health Science Center, Beijing, China.
(2)Peking University Institute of Environmental Medicine, Beijing, China.
(3)Chinese Academy of Medical Sciences, Beijing, China.
(4)Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield
Department of Population Health, University of Oxford, UK.
(5)Hainan Center for Disease Control & Prevention, Haikou, Hainan, China.
(6)Licang Center for Disease Control & Prevention, Qingdao, Shandong, China.
(7)China National Center for Food Safety Risk Assessment, Beijing, China.
(8)Department of Epidemiology, School of Public Health and Tropical Medicine,
Tulane University, New Orleans, LA, USA.
(9)Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
Background: Simultaneously adhering to multiple healthy lifestyle factors has
been related to up to 90% reduction in type 2 diabetes (T2DM) incidence in White
populations; however, little is known about whether such protective effects
persist in other non-White populations.
Methods: We examined the associations of six lifestyle factors with T2DM in the
China Kadoorie Biobank of 461 211 participants aged 30-79 years without diabetes,
cardiovascular diseases or cancer at baseline. We defined low-risk lifestyle
factors as non-smoking or having stopped for reasons other than illness; alcohol
consumption of <30 g/day; upper quarter of the physical activity level; diet rich
in vegetables and fruits, low in red meat and with some degree of replacement of
rice with wheat; body mass index (BMI) of 18.5-23.9 kg/m2; and waist-to-hip ratio
(WHR) <0.90 (men)/<0.85 (women).
Results: During a median of 7.2 years of follow-up, we identified 8784 incident
T2DM. In multivariable-adjusted analyses, two important risk factors for

developing T2DM were higher BMI and WHR. Compared with participants without any
low-risk factors, the hazard ratio [95% confidence interval (CI)] for those with
at least three low-risk factors was 0.20 (0.19, 0.22). Approximately 72.6%
(64.2%, 79.3%) of the incident diabetes were attributable to the combination of
BMI, WHR, diet and physical activity. The population attributable risk percentage
(PAR%) of diabetes appeared to be similar for men and women, and higher among
urban, older and obese participants.
Conclusions: Our findings indicate that adherence to a healthy lifestyle may
substantially lower the burden of T2DM in the Chinese population.
© The Author 2017. Published by Oxford University Press on behalf of the
International Epidemiological Association
DOI: 10.1093/ije/dyx074
PMCID: PMC5837408
7. Popul Health Metr. 2017 May 3;15(1):17. doi: 10.1186/s12963-017-0134-4.
Adult mortality of diseases and injuries attributable to selected metabolic,
lifestyle, environmental, and infectious risk factors in Taiwan: a comparative
risk assessment.
Lo WC(1)(2), Ku CC(1)(3), Chiou ST(4)(5), Chan CC(6)(7), Chen CL(8), Lai
MS(1)(2), Lin HH(9).
Author information:
(1)Graduate Institute of Epidemiology and Preventive Medicine, College of Public
Health, National Taiwan University, 17 Xuzhou Rd, Rm 706, Taipei, 10055, Taiwan.
(2)Taiwan Cancer Registry, Taipei, Taiwan.

(3)School of Health and Related Research (ScHARR), University of Sheffield,
Sheffield, UK.
(4)Health Promotion Administration, Ministry of Health and Welfare, Taipei,
Taiwan.
(5)Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
(6)Institute of Occupational Medicine and Industrial Hygiene, College of Public
Health, National Taiwan University, Taipei, Taiwan.
(7)Global Health Center, College of Public Health, National Taiwan University,
Taipei, Taiwan.
(8)Graduate Institute of Clinical Medicine, Department of Internal Medicine and
Hepatitis Research Center, National Taiwan University College of Medicine and
Hospital, Taipei, Taiwan.
(9)Graduate Institute of Epidemiology and Preventive Medicine, College of Public
Health, National Taiwan University, 17 Xuzhou Rd, Rm 706, Taipei, 10055, Taiwan.
hsienho@gmail.com.
BACKGROUND: To facilitate priority-setting in health policymaking, we compiled
the best available information to estimate the adult mortality (>30 years) burden
attributable to 13 metabolic, lifestyle, infectious, and environmental risk
factors in Taiwan.
METHODS: We obtained data on risk factor exposure from nationally representative
health surveys, cause-specific mortality from the National Death Registry, and
relative risks from epidemiological studies and meta-analyses. We applied the
comparative risk assessment framework to estimate mortality burden attributable
to individual risk factors or risk factor clusters.
RESULTS: In 2009, high blood glucose accounted for 14,900 deaths (95% UI:
11,850-17,960), or 10.4% of all deaths in that year. It was followed by tobacco
smoking (13,340 deaths, 95% UI: 10,330-16,450), high blood pressure (11,190
deaths, 95% UI: 8,190-14,190), ambient particulate matter pollution (8,600
deaths, 95% UI: 7,370-9,840), and dietary risks (high sodium intake and low
intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970-9,810).

Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI:
6,040-9,190), and 7,400 deaths (95% UI: 6,670-8,130), respectively. The
cardiometabolic risk factors of high blood pressure, high blood glucose, high
cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI:
11,220-13,020) from cardiovascular diseases. For domestic risk factors,
infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were
responsible for 6,300 deaths (95% UI: 5,610-6,980) and 3,170 deaths (95% UI:
1,860-4,490), respectively, and betel nut use was associated with 1,780 deaths
from oral, laryngeal, and esophageal cancer (95% UI: 1,190-2,360). The leading
risk factors for years of life lost were similar, but the impact of tobacco
smoking and alcohol use became larger because the attributable deaths from these
risk factors occurred among young adults aged less than 60 years.
CONCLUSIONS: High blood glucose, tobacco smoking, and high blood pressure are the
major risk factors for deaths from diseases and injuries among Taiwanese adults.
A large number of years of life would be gained if the 13 modifiable risk factors
could be removed or reduced to the optimal level.
DOI: 10.1186/s12963-017-0134-4
PMCID: PMC5415794
8. J Diabetes Res. 2018 Sep 9;2018:3274084. doi: 10.1155/2018/3274084. eCollection
2018.
Advanced Glycation End Products Increase MDM2 Expression via Transcription Factor
KLF5.
Wang P(1), Lu YC(1), Li YF(2), Wang L(1), Lee SC(1)(3).
Author information:
(1)School of Life Sciences, Shanxi University, Taiyuan, Shanxi 030006, China.
(2)Department of Oncology, The First Clinical Hospital of Shanxi Medical
University, Taiyuan, Shanxi 030006, China.
(3)Department of Bological Science, School of Life Sciences, Jiangsu Normal
University, Xuzhou, Jiangsu 221000, China.
Type 2 diabetes increases the risk for all-site cancers including colon cancer.
Diabetic patients present typical pathophysiological features including an
increased level of advanced glycation end products (AGEs), which comes from a
series of nonenzymatic reactions between sugars and biological macromolecules,
positively associated with the occurrence of diabetic complications. MDM2 is an
oncogene implicated in cancer development. The present study investigated whether
diabetes promoted MDM2 expression in colon cells and the underlying mechanisms.
Our results showed that AGE increased the protein level of MDM2 in a cell model
and promoted binding between MDM2 and Rb as well as p53, which led to degradation
of Rb and p53. KLF5 was able to bind to the regulatory sequence of the MDM2 gene,
and knockdown of the KLF5 protein level inhibited the AGE-triggered MDM2
overexpression, which indicated that KLF5 was the transcription factor for MDM2.
In a mouse model of diabetes, we found that AGE level was increased in serum. The
protein levels of both KLF5 and MDM2 were increased. KLF5 was able to bind to the
regulatory sequence of the MDM2 gene. In conclusion, our results suggest that
diabetes increases the level of AGE which enhances the expression of MDM2 via
transcription factor KLF5 in colon cells. MDM2 overexpression is a candidate
biological link between type 2 diabetes and colon cancer development.
DOI: 10.1155/2018/3274084
PMCID: PMC6151196
PMID: 30271790
9. BMJ Open Diabetes Res Care. 2018 Jul 2;6(1):e000496. doi:

10.1136/bmjdrc-2017-000496. eCollection 2018.
Adverse effect of long work hours on incident diabetes in 7065 Ontario workers
followed for 12 years.
Gilbert-Ouimet M(1)(2), Ma H(3), Glazier R(3)(4)(5)(6), Brisson C(1)(7), Mustard
C(2)(4), Smith PM(2)(4)(8).
Author information:
(1)Axe santé des populations et pratiques optimales en santé, Centre de recherche
FRQS du CHU de Québec, Québec, Canada.
(2)Institute for Work & Health, Toronto, Ontario, Canada.
(3)Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
(4)Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario,
Canada.
(5)Department of Family and Community Medicine, University of Toronto and St
Michael's Hospital, Toronto, Ontario, Canada.
(6)Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St
Michael's Hospital, Toronto, Ontario, Canada.
(7)Département de médecine sociale et préventive, Université Laval, Québec,
Canada.
(8)Department of Epidemiology and Preventive Medicine, Monash University,
Clayton, Victoria, Australia.
Objective: According to the International Diabetes Federation, the most important
challenge for prevention is now to identify social and environmental modifiable
risk factors of diabetes. In this regard, long work hours have recently been
linked with diabetes, but more high-quality prospective studies are needed. We
evaluated the relationship between long work hours and the incidence of diabetes
among 7065 workers over a 12-year period in Ontario, Canada.
Research design and methods: Data from Ontario respondents (35-74 years of age)
to the 2003 Canadian Community Health Survey were prospectively linked to the
Ontario Health Insurance Plan database for physician services and the Canadian
Institute for Health Information Discharge Abstract Database for hospital
admissions. Our sample consisted of actively employed participants with no
previous diagnoses of diabetes. Cox proportional hazard regression models were
then performed to evaluate the relationship between long work hours (≥45 hours
per week) and the incidence of diabetes.
Results: Long work hours did not increase the risk of developing diabetes among
men. However, among women, those usually working 45 hours or more per week had a
significantly higher risk of diabetes than women working between 35 and 40 hours
per week (HR: 1.63 (95% CI 1.04 to 2.57)). The effect was slightly attenuated
when adjusted for the potentially mediating factors which are smoking, leisure
time physical activity, alcohol consumption and body mass index.
Conclusion: Working 45 hours or more per week was associated with an increased
incidence of diabetes among women, but not men. Identifying modifiable risk
factors such as long work hours is of major importance to improve prevention
strategies and orient policy making.
DOI: 10.1136/bmjdrc-2017-000496
PMCID: PMC6038836
PMID: 30002856
Conflict of interest statement: Conflicts of interest: None declared.
10. J Hosp Manag Health Policy. 2018 Apr;2. pii: 17. doi: 10.21037/jhmhp.2018.04.07.
Epub 2018 Apr 26.
The affordable care act and insurance coverage for persons with diabetes in the
United States.
Brown DS(1), Delavar A(1).
Author information:
(1)Brown School, Washington University in St. Louis, St. Louis, MO, USA.
Comment on
Diabetes Care. 2018 May;41(5):956-962.
DOI: 10.21037/jhmhp.2018.04.07
PMCID: PMC6117109
PMID: 30175323
Conflict of interest statement: Footnote Conflicts of Interest: The authors have
no conflicts of interest to declare.
11. BMC Infect Dis. 2017 May 2;17(1):316. doi: 10.1186/s12879-017-2414-9.
Analysis of patients with diabetes and complicated intra-abdominal infection or
complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam.
Popejoy MW(1), Long J(2), Huntington JA(2).
Author information:
(1)Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
myra.popejoy@merck.com.
(2)Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
BACKGROUND: Diabetes mellitus and hyperglycemia are associated with increased
susceptibility to bacterial infections and poor treatment outcomes. This post hoc
evaluation of the treatment of complicated intra-abdominal infections (cIAI) and

complicated urinary tract infections (cUTI) aimed to evaluate baseline
characteristics, efficacy, and safety in patients with and without diabetes
treated with ceftolozane/tazobactam and comparators. Ceftolozane/tazobactam is an
antibacterial with potent activity against Gram-negative pathogens and is
approved for the treatment of cIAI (with metronidazole) and cUTI (including
pyelonephritis).
METHODS: Patients from the phase 3 ASPECT studies with (n = 245) and without
(n = 1802) diabetes were compared to evaluate the baseline characteristics,
efficacy, and safety of ceftolozane/tazobactam and active comparators.
RESULTS: Significantly more patients with than without diabetes were 65 years of
age or older; patients with diabetes were also more likely to weigh ≥75 kg at
baseline (57.1% vs 44.5%), to have renal impairment (48.5% vs 30.2%), or to have
APACHE II scores ≥10 (33.8% vs 17.0%). More patients with diabetes had
comorbidities and an increased incidence of complicating factors in both cIAI and
cUTI. Clinical cIAI and composite cure cUTI rates across study treatments were
lower in patients with than without diabetes (cIAI, 75.4% vs 86.1%, P = 0.0196;
cUTI, 62.4% vs 74.7%, P = 0.1299) but were generally similar between the
ceftolozane/tazobactam and active comparator treatment groups. However,
significantly higher composite cure rates were reported with
ceftolozane/tazobactam than with levofloxacin in patients without diabetes with
cUTI (79.5% vs 69.9%; P = 0.0048). Significantly higher rates of adverse events
observed in patients with diabetes were likely due to comorbidities because
treatment-related adverse events were similar between groups.
CONCLUSIONS: In this post hoc analysis, patients with diabetes in general were
older, heavier, and had a greater number of complicating comorbidities. Patients
with diabetes had lower cure rates and a significantly higher frequency of
adverse events than patients without diabetes, likely because of the higher rates
of medical complications in this subgroup. Ceftolozane/tazobactam was shown to be
at least as effective as comparators in treating cUTI and cIAI in this
population.
TRIAL REGISTRATION: cIAI, NCT01445665 and NCT01445678 (both trials registered

prospectively on September 26, 2011); cUTI, NCT01345929 and NCT01345955 (both
trials registered prospectively on April 28, 2011).
DOI: 10.1186/s12879-017-2414-9
PMCID: PMC5414364
12. PLoS One. 2018 Mar 27;13(3):e0194603. doi: 10.1371/journal.pone.0194603.
eCollection 2018.
Anti-inflammatory cytokine and angiogenic factors levels in vitreous samples of
diabetic retinopathy patients.
Tsai T(1), Kuehn S(1), Tsiampalis N(1), Vu MK(1), Kakkassery V(1), Stute G(1),
Dick HB(1), Joachim SC(1).
Author information:
(1)Experimental Eye Research Institute, Eye Hospital, Ruhr-University Bochum,
Bochum, Germany.
Evaluation of cytokines in patients with diabetic retinopathy (DR) is important
for the identification of future additive or alternative treatment options.
Therefore, vitreous samples were obtained from patients with DR and patients with
macular hole or macular pucker (control group) during 23-gauge-vitrectomy (n =
17/group). The levels of three pro-inflammatory (IL-1ß, IL-6, IFN-γ) and
pleiotropic cytokines (IL-2, IL-4, IL-13) as well as VEGF, VEGF-A, and PGF were
measured using an enzyme linked immunosorbent assay (ELISA). IL-1ß (p = 0.02) and
IFN-γ (p = 0.04), two of the three tested pro-inflammatory cytokines, were
elevated in the DR patients, while IL-6 (p = 0.51) level was comparable in both
groups. Moreover, in DR samples, a trend towards an IL-13 down-regulation (p =

0.36) was observable. The IL-2 (p = 0.62) and IL-4 (p = 0.78) levels were
comparable in both groups. All analyzed angiogenetic factors were up-regulated in
DR patients (VEGF: p<0.001; VEGF-A: p = 0.002; PGF: p<0.001). The up-regulation
of angiogenetic factors underline their importance in DR development. However,
the interaction of the other cytokines showed an interesting pattern.
Pro-inflammatory cytokines were also up-regulated, which could be evidence for
inflammation processes in the diabetic retina. Furthermore, it seems that a
counter response of immunomodulatory cytokines is in an initial process, but not
strong enough to regulate the processes. Therefore, to support these
anti-inflammatory mechanisms might be additive treatment option in the future.
PMCID: PMC5870958
13. Evid Based Complement Alternat Med. 2016;2016:8243215. doi: 10.1155/2016/8243215.
Epub 2016 Aug 10.
Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of
Scoparia dulcis.
Pamunuwa G(1), Karunaratne DN(2), Waisundara VY(3).
Author information:
(1)Department of Horticulture and Landscape Gardening, Faculty of Agriculture and
Plantation Management, Wayamba University of Sri Lanka, Makandura, Gonawila, Sri
Lanka.
(2)Department of Chemistry, Faculty of Science, University of Peradeniya,
Peradeniya, Sri Lanka.
(3)Functional Food Product Development Project, National Institute of Fundamental

Studies, Hantana Road, Kandy, Sri Lanka.
Erratum in
Evid Based Complement Alternat Med. 2017;2017:2535014.
This review discusses the antidiabetic activities of Scoparia dulcis as well as
its antioxidant and anti-inflammatory properties in relation to the diabetes and
its complications. Ethnomedical applications of the herb have been identified as
treatment for jaundice, stomach problems, skin disease, fever, and kidney stones,
reproductory issues, and piles. Evidence has been demonstrated through scientific
studies as to the antidiabetic effects of crude extracts of S. dulcis as well as
its bioactive constituents. The primary mechanisms of action of antidiabetic
activity of the plant and its bioactive constituents are through α-glucosidase
inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid
A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are
some of the compounds which have been identified as responsible for these
mechanisms of action. S. dulcis has also been shown to exhibit analgesic,
antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and
antimicrobial activities. Given this evidence, it may be concluded that S. dulcis
could be promoted among the masses as an alternative and complementary therapy
for diabetes, provided further scientific studies on the toxicological and
pharmacological aspects are carried out through either in vivo or clinical means.
DOI: 10.1155/2016/8243215
PMCID: PMC4995349
PMID: 27594892
14. Br J Clin Pharmacol. 2016 Dec;82(6):1613-1624. doi: 10.1111/bcp.13069. Epub 2016
Aug 16.
Application of the integrated glucose-insulin model for cross-study
characterization of T2DM patients on metformin background treatment.
Parkinson J(1), Hamrén B(1), Kjellsson MC(2), Skrtic S(1)(3).
Author information:
(1)Cardiovascular & Metabolic Disease, Innovative Medicines and Early Development
Biotech Unit, AstraZeneca, Mölndal, 431 83, Sweden.
(2)Pharmacometrics Research Group, Department of Pharmaceutical Biosciences,
Uppsala University, Sweden.
(3)Department of Endocrinology, Sahlgrenska University Hospital and Institute of
Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
AIM: The integrated glucose-insulin (IGI) model is a semi-mechanistic
physiological model which can describe the glucose-insulin homeostasis system
following various glucose challenge settings. The aim of the present work was to
apply the model to a large and diverse population of metformin-only-treated type
2 diabetes mellitus (T2DM) patients and identify patient-specific covariates.
METHODS: Data from four clinical studies were pooled, including glucose and
insulin concentration-time profiles from T2DM patients on stable treatment with
metformin alone following mixed-meal tolerance tests. The data were collected
from a wide range of patients with respect to the duration of diabetes and level
of glycaemic control.
RESULTS: The IGI model was expanded by four patient-specific covariates. The
level of glycaemic control, represented by baseline glycosylated haemoglobin was
identified as a significant covariate for steady-state glucose, insulin-dependent
glucose clearance and the magnitude of the incretin effect, while baseline body
mass index was a significant covariate for steady-state insulin levels. In
addition, glucose dose was found to have an impact on glucose absorption rate.
The developed model was used to simulate glucose and insulin profiles in
different groups of T2DM patients, across a range of glycaemic control, and it

was found accurately to characterize their response to the standard oral glucose
challenge.
CONCLUSIONS: The IGI model was successfully applied to characterize differences
between T2DM patients across a wide range of glycaemic control. The addition of
patient-specific covariates in the IGI model might be valuable for the future
development of antidiabetic treatment and for the design and simulation of
clinical studies.
© 2016 The British Pharmacological Society.
DOI: 10.1111/bcp.13069
PMCID: PMC5099540
15. PLoS One. 2017 Jun 22;12(6):e0179790. doi: 10.1371/journal.pone.0179790.
eCollection 2017.
Applying artificial intelligence to disease staging: Deep learning for improved
staging of diabetic retinopathy.
Takahashi H(1), Tampo H(1), Arai Y(1), Inoue Y(1), Kawashima H(1).
Author information:
(1)Department of Ophthalmology, Jichi Medical University, 3311-1 Yakushiji,
Shimotsuke-shi, Tochigi, Japan.
PURPOSE: Disease staging involves the assessment of disease severity or
progression and is used for treatment selection. In diabetic retinopathy, disease
staging using a wide area is more desirable than that using a limited area. We
investigated if deep learning artificial intelligence (AI) could be used to grade

diabetic retinopathy and determine treatment and prognosis.
METHODS: The retrospective study analyzed 9,939 posterior pole photographs of
2,740 patients with diabetes. Nonmydriatic 45° field color fundus photographs
were taken of four fields in each eye annually at Jichi Medical University
between May 2011 and June 2015. A modified fully randomly initialized GoogLeNet
deep learning neural network was trained on 95% of the photographs using manual
modified Davis grading of three additional adjacent photographs. We graded 4,709
of the 9,939 posterior pole fundus photographs using real prognoses. In addition,
95% of the photographs were learned by the modified GoogLeNet. Main outcome
measures were prevalence and bias-adjusted Fleiss' kappa (PABAK) of AI staging of
the remaining 5% of the photographs.
RESULTS: The PABAK to modified Davis grading was 0.64 (accuracy, 81%; correct
answer in 402 of 496 photographs). The PABAK to real prognosis grading was 0.37
(accuracy, 96%).
CONCLUSIONS: We propose a novel AI disease-staging system for grading diabetic
retinopathy that involves a retinal area not typically visualized on fundoscopy
and another AI that directly suggests treatments and determines prognoses.
PMCID: PMC5480986
16. Diabetes Care. 2018 Jun;41(6):1312-1320. doi: 10.2337/dc17-2010.
Aspects of Multicomponent Integrated Care Promote Sustained Improvement in
Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis.
Lim LL(1)(2)(3), Lau ESH(1)(2), Kong APS(1)(2)(4), Davies MJ(5), Levitt NS(6),
Eliasson B(7), Aguilar-Salinas CA(8), Ning G(9), Seino Y(10), So WY(1)(2)(4),
McGill M(11), Ogle GD(12), Orchard TJ(13), Clarke P(14), Holman RR(15), Gregg
EW(16), Gagliardino JJ(17), Chan JCN(18)(2)(4).
Author information:
(1)Department of Medicine and Therapeutics, The Chinese University of Hong Kong,
Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China.
(2)Asia Diabetes Foundation, Prince of Wales Hospital, Shatin, Hong Kong Special
Administrative Region, China.
(3)Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
(4)Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong
Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region,
China.
(5)Diabetes Research Centre, University of Leicester, Leicester, U.K.
(6)Department of Medicine, University of Cape Town, Cape Town, South Africa.
(7)Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
(8)Department of Endocrinology and Metabolism, National Institute of Medical
Sciences and Nutrition, Mexico City, Mexico.
(9)Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
(10)Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power
Hospital, Osaka, Japan.
(11)Diabetes Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney,
Australia.
(12)International Diabetes Federation Life for a Child Programme, Sydney,
Australia.
(13)Department of Epidemiology, Graduate School of Public Health, University of
Pittsburgh, Pittsburgh, PA.
(14)Melbourne School of Population and Global Health, University of Melbourne,
Melbourne, Australia.
(15)Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and
Metabolism, University of Oxford, Oxford, U.K.
(16)Division of Diabetes Translation, National Center for Chronic Disease

Prevention and Health Promotion, Centers for Disease Control and Prevention,
Atlanta, GA.
(17)Center of Experimental and Applied Endocrinology, National Scientific and
Technical Research Council, National University of La Plata, La Plata, Argentina.
Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China
jchan@cuhk.edu.hk.
OBJECTIVE: The implementation of the Chronic Care Model (CCM) improves health
care quality. We examined the sustained effectiveness of multicomponent
integrated care in type 2 diabetes.
RESEARCH DESIGN AND METHODS: We searched PubMed and Ovid MEDLINE (January
2000-August 2016) and identified randomized controlled trials comprising two or
more quality improvement strategies from two or more domains (health system,
health care providers, or patients) lasting ≥12 months with one or more clinical
outcomes. Two reviewers extracted data and appraised the reporting quality.
RESULTS: In a meta-analysis of 181 trials (N = 135,112), random-effects modeling
revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1
mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to
-1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL
cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in
patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L;
Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North
America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12
months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg,
Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies,
Pdifference = 0.049). Patients with median age <60 years had greater HbA1c
reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference
= 0.029). Team change, patient education/self-management, and improved
patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9
mmol/mol]).
CONCLUSIONS: Despite the small effect size of multicomponent integrated care (in
part attenuated by good background care), team-based care with better information
flow may improve patient-provider communication and self-management in patients
who are young, with suboptimal control, and in low-resource settings.
© 2018 by the American Diabetes Association.
DOI: 10.2337/dc17-2010
PMCID: PMC5961399 [Available on 2019-06-01]
eCollection 2018.
Assessing the influence of health systems on Type 2 Diabetes Mellitus awareness,
treatment, adherence, and control: A systematic review.
Ong SE(1), Koh JJK(1), Toh SES(2)(3), Chia KS(1), Balabanova D(4), McKee M(4),
Perel P(4)(5), Legido-Quigley H(1)(4).
Author information:
(1)Saw Swee Hock School of Public Health, National University of Singapore,
Singapore, Singapore.
(2)Yong Loo Lin School of Medicine, National University of Singapore, Singapore,
Singapore.
(3)Division of Endocrinology, Department of Medicine, National University Health
System, Singapore, Singapore.
(4)London School of Hygiene and Tropical Medicine, London, United Kingdom.
(5)World Heart Federation, Geneva, Switzerland.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is reported to affect one in 11
adults worldwide, with over 80% of T2DM patients residing in low-to-middle-income
countries. Health systems play an integral role in responding to this increasing
global prevalence, and are key to ensuring effective diabetes management. We
conducted a systematic review to examine the health system-level factors
influencing T2DM awareness, treatment, adherence, and control.
METHODS AND FINDINGS: A protocol for this study was published on the PROSPERO
international prospective register of systematic reviews (PROSPERO 2016:
CRD42016048185). Studies included in this review reported the effects of health
systems factors, interventions, policies, or programmes on T2DM control,
awareness, treatment, and adherence. The following databases were searched on 22
February 2017: Medline, Embase, Global health, LILACS, Africa-Wide, IMSEAR,
IMEMR, and WPRIM. There were no restrictions on date, language, or study designs.
Two reviewers independently screened studies for eligibility, extracted the data,
and screened for risk of bias. Thereafter, we performed a narrative synthesis. A
meta-analysis was not conducted due to methodological heterogeneity across
different aspects of included studies. 93 studies were included for qualitative
synthesis; 7 were conducted in LMICs. Through this review, we found two key
health system barriers to effective T2DM care and management: financial
constraints faced by the patient and limited access to health services and
medication. We also found three health system factors that facilitate effective
T2DM care and management: the use of innovative care models, increased pharmacist
involvement in care delivery, and education programmes led by healthcare
professionals.
CONCLUSIONS: This review points to the importance of reducing, or possibly
eliminating, out-of-pocket costs for diabetes medication and self-monitoring
supplies. It also points to the potential of adopting more innovative and
integrated models of care, and the value of task-sharing of care with
pharmacists. More studies which identify the effect of health system arrangements
on various outcomes, particularly awareness, are needed.

PMCID: PMC5875848
18. PLoS One. 2016 Aug 15;11(8):e0160809. doi: 10.1371/journal.pone.0160809.
eCollection 2016.
Association between Depressive Symptoms and Cognitive Function in Persons with
Diabetes Mellitus: A Systematic Review.
Danna SM(1)(2), Graham E(1)(2), Burns RJ(2)(3), Deschênes SS(2)(3), Schmitz
N(1)(2)(3)(4).
Author information:
(1)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, Montreal, Quebec, Canada.
(2)Douglas Mental Health University Institute, Montreal, Quebec, Canada.
(3)Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
(4)Montreal Diabetes Research Centre, Montreal, Quebec, Canada.
Depression and diabetes are independent risk factors for one another, and both
are associated with increased risk of cognitive decline. Diabetes patients with
lower cognitive function are more likely to suffer poorer health outcomes.
However, the role of depression in cognitive decline among people with diabetes
is not well understood. This systematic review assessed whether adults with
comorbid diabetes and depression or depressive symptoms exhibit greater cognitive
decline relative to individuals with diabetes alone. Searches were run in CINAHL,
the Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, and PubMed
(MEDLINE) with no time or language restrictions. Studies were eligible for
inclusion if they were of any quantitative study design, included participants

aged 18 years or older with diabetes mellitus of which some must have presented
with current depression, and measured cognition as an outcome. The Cochrane
Collaboration's Risk Of Bias In Non-randomized Studies-of Interventions tool was
used for quality assessment of each study and its collected outcome. Fifteen
articles were included in the final analysis. The high degree of heterogeneity in
exposures, outcomes, and participant characteristics precluded a meta-analysis of
any of the studies, and the risk of bias observed in these studies limits the
strength of the evidence. Nonetheless, this review found the presence of comorbid
depression was associated with poorer cognitive outcomes than for persons with
diabetes alone. While large-scale preventive efforts must address epidemic levels
of diabetes and its comorbidities, on the patient level healthcare professionals
must be cognizant of the added difficulties that depression poses to patients and
the extra support required to management diabetes in these cases. This systematic
review is registered with the University of York Centre for Reviews and
Dissemination under registration number 2015:CRD42015025122.
PMCID: PMC4985066
19. Liver Int. 2017 Feb;37(2):251-258. doi: 10.1111/liv.13241. Epub 2016 Sep 16.
Association between diabetes mellitus and cirrhosis mortality: the Singapore
Chinese Health Study.
Goh GB(1)(2), Pan A(3)(4), Chow WC(1)(2), Yuan JM(5)(6), Koh WP(2)(7).
Author information:
(1)Department of Gastroenterology & Hepatology, Singapore General Hospital,
(2)Duke-NUS Medical School, Singapore, Singapore.
(3)Department of Epidemiology and Biostatistics, School of Public Health, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan, Hubei,
China.
(4)Key Laboratory of Environment and Health, Ministry of Education, and State Key
Laboratory of Environmental Health (incubation), School of Public Health, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan, Hubei,
China.
(5)Division of Cancer Control and Population Science, University of Pittsburgh
Cancer Institute, Pittsburgh, PA, USA.
(6)Department of Epidemiology, University of Pittsburgh Graduate School of Public
Health, Pittsburgh, PA, USA.
Comment in
Liver Int. 2017 Mar;37(3):466.
Liver Int. 2017 Mar;37(3):467.
BACKGROUND & AIM: Diabetes mellitus has been linked to cirrhosis-related
mortality in Western populations, but less is known about this relationship in
Asian populations. We studied the impact of diabetes on the risk of cirrhosis
mortality in a population-based cohort among Chinese in Singapore.
METHODS: We used data collected and analysed from the Singapore Chinese Health
Study, a prospective community-based cohort of 63 275 subjects aged 45-74 years
during enrolment between 1993 and 1998. Information on diet, lifestyle and
medical history was collected via structured questionnaire. Mortality cases from
cirrhosis in the cohort were identified via linkage with nationwide death
registry up to 31 December 2014. Cox proportional regression models were used to
estimate the associations with adjustment for risk factors of cirrhosis.
RESULTS: After a mean follow-up of 16.9 years, there were 133 deaths from
cirrhosis. Diabetes was associated with an increased risk of cirrhosis mortality
(hazard ratio [HR]: 2.80; 95% confidence interval [CI]: 2.04-3.83), and for both
viral (HR: 2.20; 95% CI: 1.18-4.11) and non-viral hepatitis-related cirrhosis
mortality (HR: 3.06; 95% CI: 2.13-4.41). The association between diabetes and
non-viral hepatitis-related cirrhosis mortality was stronger among participants
of body mass index (BMI) less than 23 kg/m2 (HR: 7.11; 95% CI: 3.42-14.79)
compared to heavier individuals (HR: 2.28; 95% CI: 1.20-4.35) (Pinteraction
=0.02).
CONCLUSION: Diabetes is a risk factor for cirrhosis mortality, especially for
non-viral hepatitis-related cirrhosis in population with BMI considered low or
normal in Asia.
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
DOI: 10.1111/liv.13241
PMCID: PMC5225025
20. J Clin Diagn Res. 2017 Jul;11(7):LC18-LC22. doi: 10.7860/JCDR/2017/28221.10286.
Epub 2017 Jul 1.
Association between Socioeconomic Status and Diabetes Mellitus: The National
Socioeconomics Survey, 2010 and 2012.
Suwannaphant K(1), Laohasiriwong W(2), Puttanapong N(3), Saengsuwan J(4), Phajan
T(5).
Author information:
(1)Student, Faculty of Public Health, Khon Kaen University, Thailand.
(2)Associate Professor, Department of Public Health, Enhancing Quality of Life

for Working, Khon Kaen, Thailand.
(3)Assistant Professor, Department of Economics, Thammasat University, Bangkok,
Thailand.
(4)Associate Professor, Department of Public Health, Khon Kaen, Thailand.
(5)Instructor, Department of Public Health, Sirindorn College of Public Health,
Khon Kaen, Thailand.
INTRODUCTION: The prevalence of Diabetes Mellitus (DM) is increasing, globally.
However, studies on the association between Socioeconomic Status (SES) factors
and DM have mostly been conducted in specific areas with rather small sample
sizes or not with nationally representative samples. Their results have also been
inconclusive regarding whether SES has any influence on DM or not.
AIM: To determine the association between SES and DM in Thailand.
MATERIALS AND METHODS: This study utilized the data from the National
socioeconomics survey, a cross-sectional study conducted by the National
Statistical Office (NSO) in 2010 and 2012. A total of 17,045 and 16,903
participants respectively who met the inclusion criteria were included in this
study. The information was collected by face-to-face interview with structured
questionnaires. Multilevel mixed-effects logistic regression analysis was
performed to determine the potential socioeconomic factors associated with DM.
RESULTS: The prevalence of DM was 3.70% (95% CI: 3.36 to 4.05) and 8.11% (95%CI:
6.25 to 9.74) in 2010 and 2012 respectively and the prevalence of DM in 2012 was
1.36 times (95% CI: 1.25 to 1.48) when compared with 2010. The multilevel
mixed-effects logistic regression observed that odds of having DM were
significantly higher among those who aged 55-64 years old in 2010 and 65 years
old or greater in 2012 (ORadj = 18.13; 95%CI: 9.11 to 36.08, ORadj 31.69; 95%CI:
20.78 to 48.33, respectively), females (ORadj = 2.09; 95%CI: 1.66 to 2.62, ORadj
= 1.77; 95%CI: 1.54 to 2.05, respectively), and had lower education attainment
(ORadj = 5.87; 95%CI: 4.70 to 7.33, ORadj= 1.22; 95%CI: 1.04 to 1.45,
respectively) were also found to be associated with DM .
CONCLUSION: The study indicated that SES has been associated with DM. Those with
female gender, old age and low educational attainment were vulnerable to DM.
DOI: 10.7860/JCDR/2017/28221.10286
PMCID: PMC5583803
PMID: 28892937
21. J Diabetes Res. 2017;2017:5850879. doi: 10.1155/2017/5850879. Epub 2017 Jul 9.
The Association between Type 2 Diabetes Mellitus and Thyroid Cancer.
Seo YG(1), Choi HC(2), An AR(3), Park DJ(4), Park YJ(4), Lee KE(5), Park
SK(6)(7)(8), Hwang Y(6)(7)(8), Cho B(3)(9)(10).
Author information:
(1)Department of Family Medicine, Hallym University Sacred Heart Hospital,
Anyang, Gyeonggi-do 14068, Republic of Korea.
(2)Department of Family Medicine, Healthcare System Gangnam Center, Seoul
National University Hospital, Seoul 03080, Republic of Korea.
(3)Department of Family Medicine, Center for Health Promotion and Optimal Aging,
Health Promotion Center for Cancer Survivor, Seoul National University Hospital,
Seoul 03080, Republic of Korea.
(4)Department of Internal Medicine, Seoul National University College of
Medicine, Seoul 03080, Republic of Korea.
(5)Department of Surgery, Seoul National University Hospital & College of
(6)Department of Preventive Medicine, Seoul National University College of
(7)Department of Biomedical Science, Seoul National University Graduate School,
Seoul 03080, Republic of Korea.
(8)Cancer Research Institute, Seoul National University, Seoul 03080, Republic of

Korea.
(9)Advanced Institutes of Convergence Technology, Seoul National University,
Suwon, Gyeonggi-do 16229, Republic of Korea.
(10)Institute on Aging, Seoul National University College of Medicine, Seoul
03080, Republic of Korea.
AIM: The incidence of thyroid cancer is increasing worldwide. The prevalence of
type 2 diabetes mellitus (T2DM) is also increasing. Therefore, we aimed to
analyze the effect of T2DM on thyroid cancer.
METHODS: A case-control study was performed. A total of 415 healthy controls with
thyroid ultrasound screening and physician consultation were selected from the
Thyroid Cancer Longitudinal Study (T-CALOS). Among patients with thyroid cancer
who were enrolled in T-CALOS, 415 patients were matched to the control group
according to age and sex. We assessed the effects of T2DM, T2DM duration, and
T2DM medication on thyroid cancer.
RESULTS: Women with T2DM had lower odds of thyroid cancer than women without T2DM
(odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.20-0.81). Individuals
receiving T2DM medication had higher odds of thyroid cancer compared to those
without T2DM medication (OR: 5.21, 95% CI: 1.58-17.15). Individuals with T2DM
duration <6 years had lower odds of thyroid cancer compared to those without T2DM
(OR: 0.58, 95% CI: 0.34-0.97).
CONCLUSIONS: Individuals with early T2DM are presumed to have a low incidence of
thyroid cancer, and this effect seems to last up to 6 years after diagnosis of
T2DM.
DOI: 10.1155/2017/5850879
PMCID: PMC5523441
22. BMJ Open. 2018 Oct 4;8(9):e021143. doi: 10.1136/bmjopen-2017-021143.

Association of neighbourhood socioeconomic status and diabetes burden using
electronic health records in Madrid (Spain): the HeartHealthyHoods study.
Bilal U(1)(2)(3), Hill-Briggs F(1)(4)(5), Sánchez-Perruca L(6)(7), Del
Cura-González I(7)(8)(9), Franco M(1)(2).
Author information:
(1)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,
Baltimore, Maryland, USA.
(2)Social and Cardiovascular Epidemiology Research Group, Universidad de Alcalá,
Madrid, Spain.
(3)Urban Health Collaborative, Drexel Dornsife School of Public Health,
Philadelphia, Pennsylvania, USA.
(4)Welch Center for Prevention, Epidemiology and Clinical Research, Hopkins
Medical Institutions, Baltimore, Maryland, USA.
(5)The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
(6)Primary Care Management, Madrid Health Service, Madrid, Spain.
(7)Health Services Research on Chronic Patients Network (REDISSEC), ISCIII,
Madrid, Spain.
(8)Primary Care Research Unit, Primary Care Management. Madrid Health Service,
Madrid, Spain.
(9)Area of Preventive Medicine and Public Health, Rey Juan Carlos University,
Madrid, Spain.
OBJECTIVE: To study the association between neighbourhood socioeconomic status
and diabetes prevalence, incidence, and control in the entire population of
northeastern Madrid, Spain.
SETTING: Electronic health records of the primary-care system in four districts
of Madrid (Spain).
PARTICIPANTS: 269 942 people aged 40 or older, followed from 2013 to 2014.

EXPOSURE: Neighbourhoodsocioeconomic status (NSES), measured using a composite
index of seven indicators from four domains of education, wealth, occupation and
living conditions.
PRIMARY OUTCOME MEASURES: Diagnosis of diabetes based on ICPC-2 codes and
glycated haemoglobin (HbA1c %).
RESULTS: In regression analyses adjusted by age and sex and compared with
individuals living in low NSES neighbourhoods, men living in medium and high NSES
neighbourhoods had 10% (95% CI: 6% to 15%) and 29% (95% CI: 25% to 32%) lower
prevalence of diabetes, while women had 27% (95% CI: 23% to 30%) and 50% (95% CI:
47% to 52%) lower prevalence of diabetes. Moreover, the hazard of diabetes in men
living in medium and high NSES neighbourhoods was 13% (95% CI: 1% to 23%) and 20%
(95% CI: 9% to 29%) lower, while the hazard of diabetes in women living in medium
and high NSES neighbourhoods was 17% (95% CI: 3% to 29%) and 31% (95% CI: 20% to
41%) lower. Individuals living in medium and high SES neighbourhoods had 8% (95%
CI: 2% to 15%) and 15% (95% CI: 9% to 21%) lower prevalence of lack of diabetes
control, and a decrease in average HbA1c % of 0.05 (95% CI: 0.01 to 0.10) and
0.11 (95% CI: 0.06 to 0.15).
CONCLUSIONS: Diabetes prevalence, incidence and lack of control increased with
decreasing NSES in a southern European city. Future studies should provide
mechanistic insights and targets for intervention to address this health
inequity.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No
commercial re-use. See rights and permissions. Published by BMJ.
DOI: 10.1136/bmjopen-2017-021143
PMCID: PMC6173235
PMID: 30287604
Conflict of interest statement: Competing interests: None declared.

23. Clin Infect Dis. 2018 Feb 10;66(5):699-705. doi: 10.1093/cid/cix852.
Association of Obesity, Diabetes, and Risk of Tuberculosis: Two Population-Based
Cohorts.
Lin HH(1), Wu CY(1), Wang CH(1), Fu H(1)(2), Lönnroth K(3), Chang YC(4)(5), Huang
YT(6).
Author information:
(1)Institute of Epidemiology and Preventive Medicine, National Taiwan University,
Taipei, Taiwan.
(2)Department of Infectious Disease Epidemiology, Imperial College London, United
Kingdom.
(3)Stop TB Department, World Health Organization, Geneva, Switzerland.
(4)Graduate Institute of Medical Genomics and Proteomics, National Taiwan
University.
(5)Department of Internal Medicine, National Taiwan University Hospital.
(6)Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Background: Mounting data have revealed that body mass index (BMI) is inversely
associated with risk of active tuberculosis. The inverse association presents a
"paradox" with regard to diabetes, because obesity is a major determinant of
diabetes, and diabetes is a well-known risk factor for tuberculosis.
Methods: We conducted 2 population-based cohort studies involving 167392
participants. The main exposure was BMI and diabetes ascertained at baseline.
Occurrence of incident tuberculosis was ascertained from Taiwan's National
Tuberculosis Registry. We conducted a causal mediation analysis and a joint
effects analysis to characterize the relationship between BMI, diabetes, and
tuberculosis.
Results: During a median of >7 years of follow-up, 491 individuals developed

incident tuberculosis. Compared with normal-weight individuals, obese individuals
(>30 kg/m2) had a 67% (95% confidence interval [CI], -3% to -90%) and 64%
(31%-81%) reduction in tuberculosis hazard in the 2 cohorts. In the causal
mediation analysis, obesity had a harmful effect on tuberculosis mediated through
diabetes (0.8% and 2.7% increased odds in the 2 cohorts, respectively) but had a
strongly protective effect not mediated through diabetes (72% and 67% decreased
odds, respectively). Individuals who were simultaneously obese and diabetic had a
lower but statistically insignificant risk of tuberculosis (adjusted hazard
ratio, 0.30; 95% CI, .08-1.22) compared with nondiabetic normal-weight
individuals.
Conclusions: Our analyses revealed that the relationship between obesity,
diabetes, and risk of tuberculosis was complex and nonlinear. Better
understanding of the interplay between host metabolism and tuberculosis
immunology may lead to novel therapeutic or preventive strategies.
© The Author 2017. Published by Oxford University Press for the Infectious
Diseases Society of America.
DOI: 10.1093/cid/cix852
PMCID: PMC5850624
PMID: 29029077
24. Rev Diabet Stud. 2018 Winter;14(4):381-389. doi: 10.1900/RDS.2017.14.381. Epub
2018 Mar 10.
Association of Socio-Environmental Determinants with Diabetes Prevalence in the
Athens Metropolitan Area, Greece: A Spatial Analysis.
Faka A(1), Chalkias C(1), Montano D(2), Georgousopoulou EN(3), Tripitsidis A(1),
Koloverou E(3), Tousoulis D(4), Pitsavos C(4), Panagiotakos DB(3).

Author information:
(1)Department of Geography, School of Environment, Geography and Applied
Economics, Harokopio University, Athens, Greece.
(2)Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University, Ulm,
Germany.
(3)Department of Nutrition and Dietetics, School of Health Science and Education,
Harokopio University, 17671 Athens, Greece.
(4)First Cardiology Clinic, School of Medicine, University of Athens, Greece.
OBJECTIVES: The aim of this study was to investigate the spatial variation of
diabetes in relation to the geographical variability of socio-environmental
characteristics in the urban districts of Athens.
METHODS: A sample of 2,445 individuals from the greater area of Athens was
randomly enrolled in the ATTICA study between 2001 and 2002. Diabetes was defined
according to American Diabetes Association criteria. Geographical and statistical
analyses were applied to examine the relationship between diabetes prevalence and
factors related to education, economic status, population density, immigrant
status, and availability of urban green areas. Diabetes prevalence and
socio-environmental factor mapping was based on the Geographic Information
Systems (GIS) technology. Variograms and spatial quasi-Poisson regression
analysis evaluated the associations of diabetes with the socio-environmental
variables at the municipal level.
RESULTS: According to the geographical analysis and mapping, the highest
proportions of people with diabetes were found in the West sector and in one
district of the East and South sector each. Regression analysis revealed that the
proportion of inhabitants with higher education is negatively correlated with
diabetes prevalence in the regional areas of Athens.
CONCLUSIONS: The study revealed that socio-environmental status in residential
areas, especially educational and economic levels, is correlated with diabetes
prevalence at the aggregate level. These correlations may reflect socio-economic

segregation patterns at the district level, and different prevalence rates of
diabetes among individuals with higher income and educational levels.
DOI: 10.1900/RDS.2017.14.381
PMID: 29590231
25. Nutr Diabetes. 2018 Jan 17;8(1):7. doi: 10.1038/s41387-017-0012-y.
Associations between body mass index and the risk of renal events in patients
with type 2 diabetes.
Mohammedi K(1)(2)(3), Chalmers J(4), Herrington W(5), Li Q(1), Mancia G(6), Marre
M(2)(3)(7), Poulter N(8), Rodgers A(1), Williams B(9), Perkovic V(1), Coresh
J(10), Woodward M(1)(10)(11).
Author information:
(1)The George Institute for Global Health, University of Sydney, Sydney,
Australia.
(2)INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France.
(3)Department of Diabetology, Endocrinology and Nutrition, Assistance Publique
Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France.
(4)The George Institute for Global Health, University of Sydney, Sydney,
Australia. chalmers@georgeinstitute.org.au.
(5)Nuffield Department of Population Health, University of Oxford, Oxford, UK.
(6)The University of Milan-Bicocca and Istituto Auxologico Italiano, Milan,
Italy.
(7)Sorbonne Paris Cité, UFR de Médecine, University Paris Diderot, Paris, France.
(8)The International Centre for Circulatory Health, National Heart and Lung
Institute, Imperial College, London, UK.

(9)Institute of Cardiovascular Sciences, University College London (UCL) and NIHR
UCL Hospitals Biomedical Research Centre, London, UK.
Johns Hopkins University, Baltimore, MD, USA.
(11)The George Institute for Global Health, University of Oxford, Oxford, UK.
BACKGROUND/OBJECTIVES: We aimed to evaluate the relationship between BMI and the
risk of renal disease in patients with type 2 diabetes in the Action in Diabetes
and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled
Evaluation (ADVANCE) study.
SUBJECTS/METHODS: Participants were divided into six baseline BMI categories:
<18.5 (underweight, n = 58); ≥18.5 to <25 (normal, n = 2894); ≥25 to <30
(overweight, n = 4340); ≥30 to <35 (obesity grade 1, n = 2265); ≥35 to <40
(obesity grade 2, n = 744); and ≥40 kg/m2 (obesity grade 3, n = 294); those
underweight were excluded. The composite outcome "major renal event" was defined
as development of new macroalbuminuria, doubling of creatinine, end stage renal
disease, or renal death. These outcomes and development of new microalbuminuria
were considered individually as secondary endpoints.
RESULTS: During 5-years of follow-up, major renal events occurred in 487 (4.6%)
patients. The risk increased with higher BMI. Multivariable-adjusted HRs (95%
CIs), compared to normal weight, were: 0.91 (0.72-1.15) for overweight; 1.03
(0.77-1.37) for obesity grade 1; 1.42 (0.98-2.07) for grade 2; and 2.16
(1.34-3.48) for grade 3 (p for trend = 0.006). These findings were similar across
subgroups by randomised interventions (intensive versus standard glucose control
and perindopril-indapamide versus placebo). Every additional unit of BMI over
25 kg/m2 increased the risk of major renal events by 4 (1-6)%. Comparable results
were observed with the risk of secondary endpoints.
CONCLUSIONS: Higher BMI is an independent predictor of major renal events in
patients with type 2 diabetes. Our findings encourage weight loss to improve
nephroprotection in these patients.

DOI: 10.1038/s41387-017-0012-y
PMCID: PMC5851426
PMID: 29343817
eCollection 2017.
Associations between serum adipocytokines and glycemic tolerance biomarkers in a
rural Chinese population.
Li X(1), Zhao Y(1), Jin Y(2), Zhang T(1), Chang X(1), Liao S(3), Xu H(1), Liu
X(1), Yang J(1), Zhang J(4), Zhang Y(1).
Author information:
(1)Department of Epidemiology, School of Public Health and Management, Ningxia
Medical University, Yinchuan, Ningxia Hui Autonomous Region, People's Republic of
China.
(2)Ningxia Center for Disease Control and Prevention, Yinchuan, Ningxia Hui
Autonomous Region, People's Republic of China.
(3)Sichuan Provincial Center for Disease Control and Prevention, Chengdu, Sichuan
Province, People's Republic of China.
(4)Department of Epidemiology, Richard M. Fairbanks School of Public Health,
Indiana University, Indianapolis, Indiana, United States of America.
Although experimental studies have shown that adiponectin and leptin modulate
glucose tolerance and insulin resistance, it remains unclear whether these
adipocytokines exert similar effects in general human populations. We evaluated
the associations of serum adiponectin and leptin with β-cell function and insulin
resistance in a population with low obesity prevalence. A cross-sectional study
of 783 rural residents, aged 25-74 years, recruited in Ningxia, China was
conducted during 2008-2012. β-cell function and insulin resistance were estimated
using the Homeostasis Model Assessment. Serum adiponectin and leptin were
measured with ELISA. Serum adiponectin concentrations (mean ± SD) were highest in
subjects with normal glucose tolerance (36.65 ± 61.13 μg/ml), intermediate in
those with impaired fasting glucose (25.92 ± 34.48 μg/ml), and lowest in those
with diabetes (15.08 ± 12.14 μg/ml) (p = 0.001). A similar pattern of differences
was found for β-cell function, whereas opposite results were observed for insulin
resistance and blood glucose. After adjustment for confounders including
metabolic syndrome components, serum adiponectin (μg/ml) was inversely associated
with β-cell function (%β) [β (95% CI): -7.57 (-12.33, -2.81)] and insulin
resistance (100/%S) [β (95% CI): -0.21 (-0.33, -0.09)]. A significant inverse
association also existed between serum leptin and β-cell function, but serum
leptin was not significantly associated with insulin resistance. The present
study suggests that adiponectin and leptin play a role in the development of
insulin resistance and diabetes independent of metabolic syndrome.
PMCID: PMC5546634
27. Prev Med Rep. 2017 Jan 26;5:285-288. doi: 10.1016/j.pmedr.2017.01.013.
eCollection 2017 Mar.
Associations of objectively measured moderate-to-vigorous-intensity physical
activity and sedentary time with all-cause mortality in a population of adults at
high risk of type 2 diabetes mellitus.
Bakrania K(1), Edwardson CL(2), Khunti K(3), Henson J(2), Stamatakis E(4), Hamer
M(5), Davies MJ(2), Yates T(2).

Author information:
(1)Department of Health Sciences, University of Leicester, Leicester General
Hospital, Leicester, Leicestershire, LE5 4PW, United Kingdom; Diabetes Research
Centre, University of Leicester, Leicester General Hospital, Leicester,
Leicestershire, LE5 4PW, United Kingdom; Leicester Diabetes Centre, University
Hospitals of Leicester, Leicester General Hospital, Leicester, Leicestershire,
LE5 4PW, United Kingdom; National Institute for Health Research (NIHR)
Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research
Unit, Diabetes Research Centre, Leicester General Hospital, Leicester,
Leicestershire, LE5 4PW, United Kingdom; National Institute for Health Research
(NIHR) Collaboration for Leadership in Applied Health Research and Care - East
Midlands (CLAHRC - EM), Diabetes Research Centre, Leicester General Hospital,
Leicester, Leicestershire, LE5 4PW, United Kingdom.
(2)Diabetes Research Centre, University of Leicester, Leicester General Hospital,
Leicester, Leicestershire, LE5 4PW, United Kingdom; Leicester Diabetes Centre,
University Hospitals of Leicester, Leicester General Hospital, Leicester,
(NIHR) Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical
Research Unit, Diabetes Research Centre, Leicester General Hospital, Leicester,
Leicestershire, LE5 4PW, United Kingdom.
(3)Diabetes Research Centre, University of Leicester, Leicester General Hospital,
Leicester, Leicestershire, LE5 4PW, United Kingdom; Leicester Diabetes Centre,
University Hospitals of Leicester, Leicester General Hospital, Leicester,
(NIHR) Collaboration for Leadership in Applied Health Research and Care - East
Midlands (CLAHRC - EM), Diabetes Research Centre, Leicester General Hospital,
Leicester, Leicestershire, LE5 4PW, United Kingdom.
(4)Charles Perkins Center, Prevention Research Collaboration, School of Public
Health, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia;
Department of Epidemiology and Public Health, Institute of Epidemiology and
Healthcare, University College London, London, WC1E 6BT, United Kingdom.

(5)National Institute for Health Research (NIHR) Leicester-Loughborough Diet,
Lifestyle and Physical Activity Biomedical Research Unit, Diabetes Research
Centre, Leicester General Hospital, Leicester, Leicestershire, LE5 4PW, United
Kingdom; School of Sport, Exercise and Health Sciences, Loughborough University,
Loughborough, Leicestershire, LE11 3TU, United Kingdom.
The relationships of physical activity and sedentary time with all-cause
mortality in those at high risk of type 2 diabetes mellitus (T2DM) are
unexplored. To address this gap in knowledge, we examined the associations of
objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and
sedentary time with all-cause mortality in a population of adults at high risk of
T2DM. In 2010-2011, 712 adults (Leicestershire, U.K.), identified as being at
high risk of T2DM, consented to be followed up for mortality. MVPA and sedentary
time were assessed by accelerometer; those with valid data (≥ 10 hours of
wear-time/day with ≥ 4 days of data) were included. Cox proportional hazards
regression models, adjusted for potential confounders, were used to investigate
the independent associations of MVPA and sedentary time with all-cause mortality.
683 participants (250 females (36.6%)) were included and during a mean follow-up
period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA
time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio
(HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p = 0.004]; indicating
that for the average adult in this cohort undertaking approximately 27.5 minutes
of MVPA/day, this benefit would be associated with only 2.75 additional minutes
of MVPA/day. Conversely, sedentary time showed no association with all-cause
mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI:
0.95, 1.03); p = 0.589]. These data support the importance of MVPA in adults at
high risk of T2DM. The association between sedentary time and mortality in this
population needs further investigation.
DOI: 10.1016/j.pmedr.2017.01.013
PMCID: PMC5279862
PMID: 28149710
28. Cell Rep. 2018 Jun 12;23(11):3286-3299. doi: 10.1016/j.celrep.2018.05.032.
Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity.
Yamamoto S(1), Kuramoto K(2), Wang N(3), Situ X(2), Priyadarshini M(4), Zhang
W(2), Cordoba-Chacon J(4), Layden BT(5), He C(6).
Author information:
(1)Department of Cell and Molecular Biology, Feinberg School of Medicine,
Northwestern University, Chicago, IL 60611, USA; Department of Microbiology,
Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Northwestern University, Chicago, IL 60611, USA.
Northwestern University, Chicago, IL 60611, USA; Key Laboratory of Industrial
Microbiology, Ministry of Education and Tianjin City, College of Biotechnology,
Tianjin University of Science and Technology, Tianjin 300457, China.
(4)Department of Medicine, Division of Endocrinology, Diabetes and Metabolism,
University of Illinois at Chicago, Chicago, IL 60612, USA.
(5)Department of Medicine, Division of Endocrinology, Diabetes and Metabolism,
University of Illinois at Chicago, Chicago, IL 60612, USA; Research and
Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, IL
60612, USA.
Northwestern University, Chicago, IL 60611, USA. Electronic address:
congcong.he@northwestern.edu.
Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to

exert similar metabolic effects in different organs. Here, we establish a model
where autophagy plays different roles in insulin-producing β cells versus
insulin-responsive cells, utilizing knockin (Becn1F121A) mice manifesting
constitutively active autophagy. With a high-fat-diet challenge, the
autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but
improved insulin sensitivity, compared to mice with normal autophagy. Autophagy
hyperactivation enhances insulin signaling, via suppressing ER stress in
insulin-responsive cells, but decreases insulin secretion by selectively
sequestrating and degrading insulin granule vesicles in β cells, a process we
term "vesicophagy." The reduction in insulin storage, insulin secretion, and
glucose tolerance is reversed by transient treatment of autophagy inhibitors.
Thus, β cells and insulin-responsive tissues require different autophagy levels
for optimal function. To improve insulin sensitivity without hampering secretion,
acute or intermittent, rather than chronic, activation of autophagy should be
considered in diabetic therapy development.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.celrep.2018.05.032
PMCID: PMC6054876
PMID: 29898399
29. BMC Endocr Disord. 2017 Sep 7;17(1):56. doi: 10.1186/s12902-017-0206-2.
Awareness and practices regarding eye diseases among patients with diabetes: a
cross sectional analysis of the CoDiab-VD cohort.
Konstantinidis L(1), Carron T(2), de Ancos E(3), Chinet L(4), Hagon-Traub I(4),
Zuercher E(2), Peytremann-Bridevaux I(2).

Author information:
(1)Jules Gonin University Eye Hospital, University of Lausanne, Avenue de France
15 - Case Postale 5143 - 1000 Lausanne 2, Lausanne, Switzerland.
lazaros.konstantinidis@fa2.ch.
(2)Institute of Social and Preventive Medicine (IUMSP), Lausanne University
Hospital and University of Lausanne, Lausanne, Switzerland.
(3)Private Practice, Morges, Switzerland.
(4)Public Health Service, Department of Health and Social Action, Canton of Vaud,
Lausanne, Switzerland.
BACKGROUND: The increasing prevalence of diabetes is leading to a rise of eye
diseases, augmenting the risk of sight-threatening complications. The aim of this
study was to evaluate prevalence, awareness and practices regarding eye diseases
among patients with diabetes in the canton of Vaud, Switzerland.
METHODS: A cohort of 323 patients with diabetes completed a self-administered
questionnaire assessing prevalence, awareness and practices regarding eye
diseases, besides health status and quality of care measures. Descriptive
analyses followed by exploratory subgroup analyses and linear regressions were
performed to investigate factors associated with awareness and practices.
RESULTS: While diabetic retinopathy was reported by 40.9% of patients with type 1
diabetes and 9.8% of patients with type 2 diabetes, 35.8% and 12.6% of all
participants reported cataract and glaucoma, respectively. Awareness that
diabetes could damage the eyes was reported by almost all participants; the
majority was also aware of the importance of glycemic control and regular eye
examination in preventing eye diseases. In contrast, only 70.5% of participants
underwent an eye examination by an ophthalmologist during the past year. Eye
examination was associated with better patients' awareness. Barriers mentioned by
patients revealed a lack of knowledge about screening guidelines, in particular
regarding the preventive nature of eye examinations.
CONCLUSIONS: Despite high levels of awareness regarding diabetic eye diseases, a
significant proportion of patients with diabetes did not report annual eye
examination. Both healthcare strategic efforts targeting the promotion of regular
eye examination and initiatives aiming at improving knowledge of screening
guidelines should be encouraged.
TRIAL REGISTRATION: ClinicalTrials.gov on 9th July 2013, identifier NCT01902043
(retrospectively registered).
DOI: 10.1186/s12902-017-0206-2
PMCID: PMC5590154
30. Hawaii J Med Public Health. 2017 Feb;76(2):48-54.
Awareness of Gestational Diabetes and its Risk Factors among Pregnant Women in
Samoa.
Price LA(1), Lock LJ(1), Archer LE(1), Ahmed Z(1).
Author information:
(1)Institute of Inflammation and Ageing, College of Medical and Dental Sciences,
University of Birmingham, Edgbaston, Birmingham.
Gestational diabetes mellitus (GDM) is a subtype of diabetes mellitus defined as
the development, or first recognition, of glucose intolerance during pregnancy.
The risk of developing type 2 diabetes mellitus (T2DM) is greater in mothers with
GDM compared to the general population. Preventing the development of GDM could
help lower the prevalence of T2DM and long-term morbidity in children of affected
mothers. The purpose of this study was to investigate the awareness of GDM and
its risk factors among pregnant women in Samoa, exploring where participants
obtained information, and understanding their attitudes towards diet and physical
activity. A quantitative cross-sectional study of 141 women attending Tupua

Tamasese Meaole (TTM) hospital in Apia, Samoa in May 2015 was performed.
Fifty-eight percent women were aware diabetes can occur for the first time during
pregnancy. The greatest information source was from doctors (37%, n=44) followed
by family members (22%, n=28), based on 118 respondents. Only one woman correctly
identified all four risk factors for GDM. Most women recognized eating a healthy
diet (79%) and regular physical activity (78%) to be appropriate lifestyle
changes to help prevent GDM. These findings suggest awareness of GDM among
pregnant women in Samoa is mixed, with a very small proportion having good
knowledge (based on the number of risk factors identified). We conclude that
increased education about GDM is necessary, both in hospital clinics and within
the community. By increasing awareness of GDM, it may be possible to decrease the
prevalence of T2DM in Samoa.
PMCID: PMC5304428
31. Braz J Med Biol Res. 2018;51(6):e7238. doi: 10.1590/1414-431x20187238. Epub 2018
Apr 19.
Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and
pancreatic architecture and on PPARγ expression.
Jasso-Villagomez EI(1), Garcia-Lorenzana M(2), Almanza-Perez JC(1),
Fortis-Barrera MA(1), Blancas-Flores G(1), Roman-Ramos R(1), Prado-Barragan
LA(3), Alarcon-Aguilar FJ(1).
Author information:
(1)Laboratory of Pharmacology, Department of Health Sciences, Division of Health
and Biological Sciences, Metropolitan Autonomous University of Iztapalapa, Mexico

City, Mexico.
(2)Laboratory of Tissue Neurobiology, Department of Reproduction Biology,
Division of Health and Biological Sciences, Metropolitan Autonomous University of
Iztapalapa, Mexico City, Mexico.
(3)Laboratory of Solid State Fermentation, Department of Biotechnology, Division
of Health and Biological Sciences, Metropolitan Autonomous University of
Iztapalapa, Mexico City, Mexico.
Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In
this study, we performed a composition analysis of U. dermestoides to obtain the
principal fractions, which were used to assess the effect on glycemia, liver and
pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and
alloxan-induced diabetic mice were administered fractions of chitin, protein or
fat, and the acute hypoglycemic effect was evaluated. A subacute study involving
daily administration of these fractions to diabetic mice was also performed over
30 days, after which the liver and pancreas were processed by conventional
histological techniques and stained with hematoxylin and eosin to evaluate
morphological changes. The most active fraction, the fat fraction, was analyzed
by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA
expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions
exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only
the fat fraction led to elevated insulin levels and reduced glycemia, as well as
lower intake of water and food. In the liver, we observed recovery of close
hepatic cords in the central lobule vein following treatment with the fat
fraction, while in the pancreas there was an increased density and percentage of
islets and number of cells per islet, suggesting cellular regeneration. The GC-MS
analysis of fat revealed three fatty acids as the major components. Finally,
increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes,
indicating an antidiabetic effect.
DOI: 10.1590/1414-431x20187238
PMCID: PMC5996452
32. Lancet. 2018 May 5;391(10132):1830-1841. doi: 10.1016/S0140-6736(18)30311-8. Epub
2018 Apr 16.
Before the beginning: nutrition and lifestyle in the preconception period and its
importance for future health.
Stephenson J(1), Heslehurst N(2), Hall J(3), Schoenaker DAJM(4), Hutchinson J(5),
Cade JE(5), Poston L(6), Barrett G(3), Crozier SR(7), Barker M(8), Kumaran K(9),
Yajnik CS(10), Baird J(8), Mishra GD(4).
Author information:
(1)Institute for Women's Health, University College London, London, UK.
Electronic address: judith.stephenson@ucl.ac.uk.
(2)Institute of Health and Society, Newcastle University, Newcastle upon Tyne,
UK.
(3)Institute for Women's Health, University College London, London, UK.
(4)School of Public Health, University of Queensland, Herston, QLD, Australia.
(5)Nutritional Epidemiology Group, School of Food Science and Nutrition,
University of Leeds, Leeds, UK.
(6)Department of Women and Children's Health, King's College London, St Thomas'
Hospital, London, UK.
(7)Medical Research Council Lifecourse Epidemiology Unit, University of
Southampton, Southampton General Hospital, Southampton, UK.
Southampton, Southampton General Hospital, Southampton, UK; National Institute
for Health Research Southampton Biomedical Research Centre, Southampton General
Hospital, Southampton, UK.

Southampton, Southampton General Hospital, Southampton, UK; Epidemiology Research
Unit, CSI Holdsworth Memorial Hospital, Mysore, Karnataka, India.
(10)Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune,
Maharashtra, India.
Erratum in
Lancet. 2018 May 5;391(10132):1774.
Comment in
Lancet. 2018 May 5;391(10132):1749.
A woman who is healthy at the time of conception is more likely to have a
successful pregnancy and a healthy child. We reviewed published evidence and
present new data from low-income, middle-income, and high-income countries on the
timing and importance of preconception health for subsequent maternal and child
health. We describe the extent to which pregnancy is planned, and whether
planning is linked to preconception health behaviours. Observational studies show
strong links between health before pregnancy and maternal and child health
outcomes, with consequences that can extend across generations, but awareness of
these links is not widespread. Poor nutrition and obesity are rife among women of
reproductive age, and differences between high-income and low-income countries
have become less distinct, with typical diets falling far short of nutritional
recommendations in both settings and especially among adolescents. Several
studies show that micronutrient supplementation starting in pregnancy can correct
important maternal nutrient deficiencies, but effects on child health outcomes
are disappointing. Other interventions to improve diet during pregnancy have had
little effect on maternal and newborn health outcomes. Comparatively few
interventions have been made for preconception diet and lifestyle. Improvements
in the measurement of pregnancy planning have quantified the degree of pregnancy
planning and suggest that it is more common than previously recognised. Planning
for pregnancy is associated with a mixed pattern of health behaviours before
conception. We propose novel definitions of the preconception period relating to
embryo development and actions at individual or population level. A sharper focus
on intervention before conception is needed to improve maternal and child health
and reduce the growing burden of non-communicable diseases. Alongside continued
efforts to reduce smoking, alcohol consumption, and obesity in the population, we
call for heightened awareness of preconception health, particularly regarding
diet and nutrition. Importantly, health professionals should be alerted to ways
of identifying women who are planning a pregnancy.
Copyright © 2018 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S0140-6736(18)30311-8
PMCID: PMC6075697
33. Front Pharmacol. 2017 Feb 3;8:42. doi: 10.3389/fphar.2017.00042. eCollection
2017.
Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic
Rats.
Gong J(1), Hu M(1), Huang Z(2), Fang K(1), Wang D(2), Chen Q(3), Li J(2), Yang
D(4), Zou X(1), Xu L(1), Wang K(1), Dong H(1), Lu F(1).
Author information:
(1)Institute of Integrated Traditional Chinese and Western Medicine, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China.
(2)Department of Integrated Traditional Chinese and Western Medicine, Tongji

Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China.
(3)Department of Biochemistry and Molecular Biology, Tongji Medical College,
Huazhong University of Science and Technology Wuhan, China.
Hospital, Tongji Medical College, Huazhong University of Science and
TechnologyWuhan, China; Department of Pharmacy, Hubei University of Traditional
Chinese MedicineWuhan, China.
Background: Intestinal mucosal barrier dysfunction plays an important role in the
development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline
alkaloid, is widely known to be effective for both DM and diarrhea. Here, we
explored whether the anti-diabetic effect of BBR was related to the intestine
mucosal barrier. Methods and Results: The rat model of T2DM was established by
high glucose and fat diet feeding and intravenous injection of streptozocin.
Then, those diabetic rats were treated with BBR at different concentrations for 9
weeks. The results showed, in addition to hyperglycemia and hyperlipidemia,
diabetic rats were also characterized by proinflammatory intestinal changes,
altered gut-derived hormones, and 2.77-fold increase in intestinal permeability.
However, the treatment with BBR significantly reversed the above changes in
diabetic rats, presenting as the improvement of the high glucose and triglyceride
levels, the relief of the inflammatory changes of intestinal immune system, and
the attenuation of the intestinal barrier damage. BBR treatment at a high
concentration also decreased the intestinal permeability by 27.5% in diabetic
rats. Furthermore, BBR regulated the expressions of the molecules involved in
TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats.
Conclusion: The hypoglycemic effects of BBR might be related to the improvement
in gut-derived hormones and the attenuation of intestinal mucosal mechanic and
immune barrier damages.
DOI: 10.3389/fphar.2017.00042
PMCID: PMC5290458
PMID: 28217099
34. Korean J Fam Med. 2018 May;39(3):137-146. doi: 10.4082/kjfm.2018.39.3.137. Epub
2018 May 18.
The Bidirectional Relationship between Diabetes and Depression: A Literature
Review.
Alzoubi A(1), Abunaser R(1), Khassawneh A(2), Alfaqih M(3), Khasawneh A(4), Abdo
N(2).
Author information:
(1)Department of Pharmacology, Faculty of Medicine, Jordan University of Science
and Technology, Irbid, Jordan.
(2)Department of Public Health and Community Medicine, Faculty of Medicine,
Jordan University of Science and Technology, Irbid, Jordan.
(3)Department of Physiology and Biochemistry, Faculty of Medicine, Jordan
University of Science and Technology, Irbid, Jordan.
(4)Department of Neurosciences, Faculty of Medicine, Jordan University of Science
and Technology, Irbid, Jordan.
Diabetes is a major public health problem worldwide. Depression is a serious
mental condition that decreases mental and physical functioning and reduces the
quality of life. Several lines of evidence suggest a bidirectional relationship
between diabetes and depression: diabetes patients are twice as likely to
experience depression than nondiabetic individuals. In contrast, depression
increases the risk of diabetes and interferes with its daily self-management.
Diabetes patients with depression have poor glycemic control, reduced quality of
life, and an increased risk of diabetes complications, consequently having an

increased mortality rate. Conflicting evidence exists on the potential role of
factors that may account for or modulate the relationship between diabetes and
depression. Therefore, this review aims to highlight the most notable body of
literature that dissects the various facets of the bidirectional relationship
between diabetes and depression. A focused discussion of the proposed mechanisms
underlying this relationship is also provided. We systematically reviewed the
relevant literature in the PubMed database, using the keywords "Diabetes AND
Depression". After exclusion of duplicate and irrelevant material, literature
eligible for inclusion in this review was based on meta-analysis studies,
clinical trials with large sample sizes (n≥1,000), randomized clinical trials,
and comprehensive national and cross-country clinical studies. The evidence we
present in this review supports the pressing need for long, outcome-oriented,
randomized clinical trials to determine whether the identification and treatment
of patients with these comorbid conditions will improve their medical outcomes
and quality of life.
DOI: 10.4082/kjfm.2018.39.3.137
PMCID: PMC5975983
PMID: 29788701
35. Diabetes Care. 2018 Sep;41(9):1901-1908. doi: 10.2337/dc18-0849. Epub 2018 Jul
12.
Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older
Women: The Cardiovascular Health Study.
Massera D(1), Biggs ML(2), Walker MD(3), Mukamal KJ(4), Ix JH(5), Djousse L(6),
Valderrábano RJ(7), Siscovick DS(8), Tracy RP(9), Xue X(1), Kizer JR(10).
Author information:
(1)Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.
(2)University of Washington, Seattle, WA.
(3)Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
(4)Beth Israel Deaconess Medical Center, Boston, MA.
(5)University of California San Diego, San Diego, CA.
(6)Brigham and Women's Hospital, Boston, MA.
(7)University of Miami, Miami, FL.
(8)The New York Academy of Medicine, New York, NY.
(9)University of Vermont, Burlington, VT.
(10)Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY
jorge.kizer@einstein.yu.edu.
OBJECTIVE: To investigate the relationship of osteocalcin (OC), a marker of bone
formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a
marker of bone resorption, with incident diabetes in older women.
RESEARCH DESIGN AND METHODS: The analysis included 1,455 female participants from
the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0]
years). The cross-sectional association of serum total OC and CTX levels with
insulin resistance (HOMA-IR) was examined using multiple linear regression. The
longitudinal association of both markers with incident diabetes, defined by
follow-up glucose measurements, medications, and ICD-9 codes, was examined using
multivariable Cox proportional hazards models.
RESULTS: OC and CTX were strongly correlated (r = 0.80). In cross-sectional
analyses, significant or near-significant inverse associations with HOMA-IR were
observed for continuous levels of OC (β = -0.12 per SD increment; P = 0.004) and
CTX (β = -0.08 per SD; P = 0.051) after full adjustment for demographic,
lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196
cases of incident diabetes occurred. After full adjustment, both biomarkers
exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per
SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]),
associations that were comparable in magnitude and approached or achieved

statistical significance.
CONCLUSIONS: In late postmenopausal women, lower OC and CTX levels were
associated with similarly increased risks of insulin resistance at baseline and
incident diabetes over long-term follow-up. Further research to delineate the
mechanisms linking abnormal bone homeostasis and energy metabolism could uncover
new approaches for the prevention of these age-related disorders.
DOI: 10.2337/dc18-0849
36. Psychosom Med. 2018 Apr;80(3):242-251. doi: 10.1097/PSY.0000000000000555.
Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2
Diabetes and Quantitative Glycemic Traits.
Haljas K(1), Amare AT, Alizadeh BZ, Hsu YH, Mosley T, Newman A, Murabito J,
Tiemeier H, Tanaka T, van Duijn C, Ding J, Llewellyn DJ, Bennett DA, Terracciano
A, Launer L, Ladwig KH, Cornelis MC, Teumer A, Grabe H, Kardia SLR, Ware EB,
Smith JA, Snieder H, Eriksson JG, Groop L, Räikkönen K, Lahti J.
Author information:
(1)From the Departments of Psychology and Logopedics (Haljas, Räikkönen) and
Psychology and Logopedics, Faculty of Medicine (Lahti), and Helsinki Collegium
for Advanced Studies (Lahti), University of Helsinki, Helsinki, Finland;
Department of Epidemiology (Amare, Alizadeh, Snieder), University of Groningen,
University Medical Center Groningen, Groningen, the Netherlands; Harvard Medical
School (Hsu), Boston, Massachusetts; Institute for Molecular Medicine Finland

(FIMM) (Groop), Helsinki, Finland; Lund University Diabetes Centre (Groop), Lund
University, Lund, Sweden; Department of General Practice and Primary Health Care
(Eriksson), University of Helsinki and Helsinki University Hospital; Folkhälsan
Research Center (Eriksson), Helsinki, Finland; Department of Medicine (Mosley),
University of Mississippi Medical Center, Jackson, Mississippi; Department of
Epidemiology, School of Public Health (Newman), University of Pittsburgh,
Pittsburgh, Pennsylvania; Department of Medicine, Section of General Internal
Medicine (Murabito), Boston University School of Medicine, Boston; Boston
University and National Heart, Lung, and Blood Institute's Framingham Heart
Study, Framingham, Massachusetts (Murabito); Departments of Epidemiology and
Psychiatry (Tiemeier), Erasmus University Medical Center, Rotterdam, the
Netherlands; Translational Gerontology Branch (Tanaka), National Institute on
Aging, Baltimore, Maryland; Genetic Epidemiology Unit, Department of Epidemiology
(van Duijn), Erasmus University Medical Center, Rotterdam; Centre for Medical
Systems Biology (van Duijn), Leiden, the Netherlands; Department of Internal
Medicine, Division of Geriatrics (Ding), Wake Forest University, Winston-Salem,
North Carolina; University of Exeter Medical School (Llewellyn), Exeter, UK; Rush
Alzheimer's Disease Center (Bennett), Chicago, Illinois; Florida State
University, College of Medicine (Terracciano), Tallahassee, Florida; Laboratory
of Epidemiology and Population Sciences (Launer), National Institute on Aging,
Bethesda, Maryland; Department of Psychiatry and Psychotherapy (Grabe), Helios
Hospital Stralsund; Department of Psychiatry and Psychotherapy (Grabe) and
Institute for Community Medicine (Teumer), University Medicine Greifswald; German
Center for Neurodegenerative Diseases (Grabe), Site Rostock/Greifswald,
Greifswald, Germany; Institute of Epidemiology II, Mental Health Research Unit,
Helmholtz Zentrum München (Ladwig), German Research Center for Environmental
Health, Neuherberg, Germany; Psychosomatic Medicine and Psychotherapy (Ladwig),
Universitäts-Klinikum Rechts der Isar, Technische Universität München, Munich,
Germany & German Center for Diabetes Research (DZD), München-Neuherberg, Germany;
Department of Preventive Medicine (Cornelis), Northwestern University Feinberg
School of Medicine, Chicago, Illinois; and Department of Epidemiology, School of

Public Health (Kardia, Ware, Smith), and Survey Research Center, Institute for
Social Research (Ware, Smith), University of Michigan, Ann Arbor, Michigan.
OBJECTIVE: Shared genetic background may explain phenotypic associations between
depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level,
if genetic correlation and pleiotropic loci exist between depressive symptoms and
T2D or glycemic traits.
METHODS: We estimated single-nucleotide polymorphism (SNP)-based heritability and
analyzed genetic correlation between depressive symptoms and T2D and glycemic
traits with the linkage disequilibrium score regression by combining summary
statistics of previously conducted meta-analyses for depressive symptoms by
CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients
and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model
assessment of β-cell function and insulin resistance by MAGIC consortium (N =
58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide
association study approach with summary statistics from genome-wide association
study meta-analyses and reported loci with genome-wide significant bivariate
association p value (p < 5 × 10). Biological annotation and function of
significant pleiotropic SNPs were assessed in several databases.
RESULTS: The SNP-based heritability ranged from 0.04 to 0.10 in each individual
trait. In the linkage disequilibrium score regression analyses, depressive
symptoms showed no significant genetic correlation with T2D or glycemic traits (p
> 0.37). However, we identified pleiotropic genetic variations for depressive
symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and
fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes).
CONCLUSIONS: We found no significant overall genetic correlations between
depressive symptoms, T2D, or glycemic traits suggesting major differences in
underlying biology of these traits. However, several potential pleiotropic loci
were identified between depressive symptoms, T2D, and fasting glucose, suggesting
that previously established phenotypic associations may be partly explained by
genetic variation in these specific loci.

DOI: 10.1097/PSY.0000000000000555
PMID: 29280852
37. Eur J Epidemiol. 2018 Nov;33(11):1033-1047. doi: 10.1007/s10654-018-0426-4. Epub
2018 Jul 31.
Body fatness, diabetes, physical activity and risk of kidney stones: a systematic
review and meta-analysis of cohort studies.
Aune D(1)(2)(3), Mahamat-Saleh Y(4), Norat T(5), Riboli E(6).
Author information:
(1)Department of Epidemiology and Biostatistics, School of Public Health,
Imperial College London, St. Mary's Campus, Norfolk Place, Paddington, London, W2
1PG, UK. d.aune@imperial.ac.uk.
(2)Department of Nutrition, Bjørknes University College, Oslo, Norway.
d.aune@imperial.ac.uk.
(3)Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo
University Hospital, Oslo, Norway. d.aune@imperial.ac.uk.
(4)INSERM (French National Institute for Health and Medical Research), CESP,
Gustave Roussy, Health Across Generations Team, Villejuif, France.
(5)Department of Nutrition, Bjørknes University College, Oslo, Norway.
Imperial College London, St. Mary's Campus, Norfolk Place, Paddington, London, W2
1PG, UK.
We conducted a systematic review and meta-analysis to clarify the association
between adiposity, diabetes, and physical activity and the risk of kidney stones.
PubMed and Embase were searched up to April 22nd 2018 for relevant studies.
Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated
using random effects models. Thirteen cohort studies were included. The summary
relative risk was 1.21 (95% CI 1.12-1.30, I2 = 76%, n = 8) per 5 unit increment
in BMI, 1.16 (95% CI 1.12-1.19, I2 = 0%, n = 5) per 10 cm increase in waist
circumference, 1.06 (95% CI 1.04-1.08, I2 = 67%, n = 3) per 5 kg increase in
weight and 1.12 (95% CI 1.06-1.18, I2 = 86%, n = 3) per 5 kg of weight gain. The
summary RR was 1.16 (95% CI 1.03-1.31, I2 = 51%, n = 10) for participants with
diabetes compared to participants without diabetes, and 0.93 (95% CI 0.78-1.10,
I2 = 80%, n = 4) for high vs. low physical activity. These results suggest a
positive association between adiposity and diabetes and the risk of kidney
stones, but no association with physical activity.
DOI: 10.1007/s10654-018-0426-4
PMCID: PMC6208979
38. Sci Rep. 2017 Mar 7;7:43521. doi: 10.1038/srep43521.
Body mass index trajectory patterns and changes in visceral fat and glucose
metabolism before the onset of type 2 diabetes.
Kuwahara K(1)(2), Honda T(3), Nakagawa T(3), Yamamoto S(3), Hayashi T(3), Mizoue
T(1).
Author information:
(1)National Center for Global Health and Medicine, Bureau of International Health
Cooperation, Department of Epidemiology and Prevention, Shinjuku-ku, 162-8655,
Japan.
(2)Teikyo University Graduate School of Public Health, Itabashi-ku, 173-8605,

Japan.
(3)Hitachi Health Care Center, Hitachi., Ltd., Hitachi, 317-0076, Japan.
We investigated BMI trajectory patterns before diabetes diagnosis and examined
associated changes in visceral adiposity and glucose metabolism. 23,978
non-diabetic Japanese participants (2,789 women) aged 30-64 years were assessed
with a mean follow-up of 7.6 years. Diabetes was diagnosed via fasting glucose,
HbA1c, and self-report. Latent-class trajectory analyses were performed to
identify BMI trajectories. Longitudinal changes in BMI, visceral adiposity, and
glucose metabolism were estimated using mixed models. 1,892 individuals developed
diabetes. Three distinct BMI trajectories were identified in adults developing
and not developing diabetes, respectively. Among adults developing diabetes,
47.3% were classified as "medium BMI" (n = 895), and had increased mean BMI
within the obesity category before diagnosis. The "low BMI" group (38.4%,
n = 726) had an initial mean BMI of 21.9 kg/m2, and demonstrated small weight
gain. The "high BMI" group (n = 271) were severely obese and showed greater
increase in BMI until diagnosis. All groups which developed diabetes showed
absolute and/or relative increase in visceral fat and impaired β-cell
compensation for insulin resistance. All groups not developing diabetes showed
measured variables were relatively stable during observation. These data suggest
that visceral fat gain may induce β-cell failure in compensation for insulin
resistance, resulting in diabetes regardless of obesity level.
DOI: 10.1038/srep43521
PMCID: PMC5339907
39. Nat Commun. 2018 Jun 19;9(1):2318. doi: 10.1038/s41467-018-04744-1.
Caffeine-inducible gene switches controlling experimental diabetes.

Bojar D(1), Scheller L(1), Hamri GC(2), Xie M(1), Fussenegger M(3)(4).
Author information:
(1)Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse
26, 4058, Basel, Switzerland.
(2)IUT, Département Génie Biologique, Institut Universitaire de Technologie,
F-69622, Villeurbanne Cedex, France.
26, 4058, Basel, Switzerland. fussenegger@bsse.ethz.ch.
(4)Faculty of Life Science, University of Basel, Mattenstrasse 26, CH-4058,
Basel, Switzerland. fussenegger@bsse.ethz.ch.
Programming cellular behavior using trigger-inducible gene switches is integral
to synthetic biology. Although significant progress has been achieved in
trigger-induced transgene expression, side-effect-free remote control of
transgenes continues to challenge cell-based therapies. Here, utilizing a
caffeine-binding single-domain antibody we establish a caffeine-inducible protein
dimerization system, enabling synthetic transcription factors and cell-surface
receptors that enable transgene expression in response to physiologically
relevant concentrations of caffeine generated by routine intake of beverages such
as tea and coffee. Coffee containing different caffeine concentrations
dose-dependently and reversibly controlled transgene expression by designer cells
with this caffeine-stimulated advanced regulators (C-STAR) system. Type-2
diabetic mice implanted with microencapsulated, C-STAR-equipped cells for
caffeine-sensitive expression of glucagon-like peptide 1 showed substantially
improved glucose homeostasis after coffee consumption compared to untreated mice.
Biopharmaceutical production control by caffeine, which is non-toxic, inexpensive
and only present in specific beverages, is expected to improve patient compliance
by integrating therapy with lifestyle.

DOI: 10.1038/s41467-018-04744-1
PMCID: PMC6008335
PMID: 29921872
eCollection 2017.
A camera-phone based study reveals erratic eating pattern and disrupted daily
eating-fasting cycle among adults in India.
Gupta NJ(1)(2), Kumar V(1), Panda S(3)(4).
Author information:
(1)Department of Zoology, University of Delhi, Delhi, India.
(2)Department of Zoology, MMH College, Ghaziabad, Uttar Pradesh, India.
(3)Salk Institute of Biological Sciences, La Jolla, California, United States of
America.
(4)UC San Diego Center for Circadian Biology, San Diego, California, United
States of America.
The daily rhythm of feeding-fasting and meal-timing are emerging as important
determinants of health. Circadian rhythm research in animal models and
retrospective analyses of human nutrition data have shown that reduced length of
overnight fasting or increased late night eating increases risk for metabolic
diseases including obesity and diabetes. However, the daily rhythm in eating
pattern in humans is rarely measured. Traditional methods to collect nutrition
information through food diary and food log pay little attention to the timing of
eating which may also change from day to day. We adopted a novel cell-phone based
approach to longitudinally record all events of food and beverage intake in
adults. In a feasibility study daily food-eating patterns of 93 healthy

individuals were recorded for 21 days using camera phones. Analysis of the daily
eating patterns of these individuals indicates deviation from conventional
assumption that people eat three meals-a-day within a 12 h interval. We found
that eating events are widespread throughout the day, with <30% of calories
consumed before noon and >30% consumed in evening and late night hours. There was
little difference in eating pattern between weekdays and weekends. In this cohort
more than 50% of people spread their caloric intake events over 15 h or longer.
One decile of the cohort who were spouses of shift-workers or had flexible work
schedule spread their caloric intake over 20 h. Although the nutrition quality
and diversity of food consumed is different between South-East Asian and Western
countries, such overall disruption of daily eating-fasting rhythm is similar.
Therefore, in view of hypothesis that disrupted daily eating pattern may
contribute to the global increase in metabolic diseases and modification of daily
eating pattern is a potential modifiable behavior to contain these diseases,
monitoring eating pattern is an important aspect of lifestyle.
PMCID: PMC5338776
41. Biomed Res Int. 2018 Apr 3;2018:8578394. doi: 10.1155/2018/8578394. eCollection
2018.
Cardiac Complications of Diabetes.
Abi Khalil C(1)(2), Al Suwaidi J(2), Refaat M(3), Mohammedi K(4)(5)(6).
Author information:
(1)Department of Medicine and Genetic Medicine, Weill Cornell Medicine-Qatar,
Doha, Qatar.
(2)Adult Cardiology, Heart Hospital, Hamad Medical Corporation, Doha, Qatar.
(3)Department of Internal Medicine, Cardiovascular Medicine/Cardiac
Electrophysiology, American University of Beirut Faculty of Medicine and Medical
Center, Beirut, Lebanon.
(4)Hôpital Haut-Lévêque, Service d'Endocrinologie, Diabétologie, Nutrition,
Bordeaux, France.
(5)Faculté de Médecine, Université de Bordeaux, Bordeaux, France.
(6)Centre de Recherche INSERM, Université de Bordeaux U1219 "Bordeaux Population
Health", Bordeaux, France.
DOI: 10.1155/2018/8578394
PMCID: PMC5903188
eCollection 2016.
Cardiovascular Risk Factors of Adults Age 20-49 Years in the United States,
1971-2012: A Series of Cross-Sectional Studies.
Casagrande SS(1), Menke A(1), Cowie CC(2).
Author information:
(1)Public Health Research, Social & Scientific Systems, Inc., Silver Spring,
Maryland, United States of America.
(2)Division of Diabetes, Endocrinology, and Metabolic Diseases, National
Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland,
United States of America.
BACKGROUND: The health of younger adults in the U.S. has important public health
and economic-related implications. However, previous literature is insufficient
to fully understand how the health of this group has changed over time. This
study examined generational differences in cardiovascular risk factors of younger
adults over the past 40 years.
METHODS: Data were from 6 nationally representative cross-sectional National
Health and Nutrition Examination Surveys (1971-2012; N = 44,670). Participants
were adults age 20-49 years who self-reported sociodemographic characteristics
and health conditions, and had examination/laboratory measures for hypertension,
hyperlipidemia, diabetes, obesity, and chronic kidney disease. Prevalences of
sociodemographic characteristics and health status were determined by study
period. Logistic regression was used to determine the odds [odds ratio (OR), 95%
confidence interval] of health conditions by study period: models adjusted only
for age, sex, and race, and fully adjusted models additionally adjusted for
socioeconomic characteristics, smoking, BMI, diabetes, and/or hypertension
(depending on the outcome) were assessed.
RESULTS: Participants in 2009-2012 were significantly more likely to be obese and
have diabetes compared to those in 1971-1975 (OR = 4.98, 3.57-6.97; OR = 3.49,
1.59-7.65, respectively, fully adjusted). Participants in 2009-2012 vs. 1988-1994
were significantly more likely to have had hypertension but uncontrolled
hypertension was significantly less likely (OR = 0.67, 0.52-0.86, fully
adjusted). There was no difference over time for high cholesterol, but
uncontrolled high cholesterol was significantly less likely in 2009-2012 vs.
1988-1994 (OR = 0.80, 0.68-0.94, fully adjusted). The use of hypertensive and
cholesterol medications increased while chronic kidney and cardiovascular
diseases were relatively stable.
CONCLUSIONS: Cardiovascular risk factors of younger U.S. adults have worsened
over the past 40 years, but treatment for hypertension and high cholesterol has
improved. The sub-optimal and worsening health in younger adults may have a
substantial impact on health care utilization and costs, and should be considered
when developing health care practices.

PMCID: PMC4995093
Conflict of interest statement: The affiliation between the National Institute of
Diabetes and Digestive and Kidney Diseases and Social & Scientific Systems, Inc.
does not alter our adherence to the PLOS ONE policies on sharing data and
materials.
43. Front Genet. 2017 Jun 6;8:75. doi: 10.3389/fgene.2017.00075. eCollection 2017.
β-Cell Replacement Strategies: The Increasing Need for a "β-Cell Dogma".
Vieira A(1), Druelle N(1), Avolio F(1), Napolitano T(1), Navarro-Sanz S(1),
Silvano S(1), Collombat P(1).
Author information:
(1)Centre National de la Recherche Scientifique, Institut National de la Santé et
de la Recherche Médicale, iBV, Université Côte d'AzurNice, France.
Type 1 diabetes is an auto-immune disease resulting in the loss of pancreatic
β-cells and, consequently, in chronic hyperglycemia. Insulin supplementation
allows diabetic patients to control their glycaemia quite efficiently, but
treated patients still display an overall shortened life expectancy and an
altered quality of life as compared to their healthy counterparts. In this
context and due to the ever increasing number of diabetics, establishing
alternative therapies has become a crucial research goal. Most current efforts
therefore aim at generating fully functional insulin-secreting β-like cells using
multiple approaches. In this review, we screened the literature published since
2011 and inventoried the selected markers used to characterize insulin-secreting

cells generated by in vitro differentiation of stem/precursor cells or by means
of in vivo transdifferentiation. By listing these features, we noted important
discrepancies when comparing the different approaches for the initial
characterization of insulin-producing cells as true β-cells. Considering the
recent advances achieved in this field of research, the necessity to establish
strict guidelines has become a subject of crucial importance, especially should
one contemplate the next step, which is the transplantation of in vitro or ex
vivo generated insulin-secreting cells in type 1 diabetic patients.
DOI: 10.3389/fgene.2017.00075
PMCID: PMC5459879
PMID: 28634486
44. BMJ Open Diabetes Res Care. 2017 Jan 23;5(1):e000327. doi:
The changing landscape of diabetes prevalence among first-generation Asian
immigrants in California from 2003 to 2013.
Fan W(1), Lee DH(1), Billimek J(2), Choi S(3), Wang PH(1).
Author information:
(1)Department of Medicine , UC Irvine Diabetes Center, School of Medicine,
University of California , Irvine, California , USA.
(2)Health Policy Research Institute, School of Nursing, University of California
, Irvine, California , USA.
(3)UCLA , School of Nursing , Los Angeles, California , USA.
OBJECTIVE: The prevalence of diabetes mellitus (DM) is increasing rapidly,
particularly in Asia. Asian immigrants in Western countries are a fast-growing

population who carry both intrinsic risks due to their genetic background and
extrinsic risks associated with Western lifestyles. However, recent trends in
diabetes prevalence and associated risk factors among Asian immigrants in the USA
are not well understood.
RESEARCH DESIGN AND METHODS: We examined adults aged 18 and older from the recent
California Health Interview Survey data sets from 2003 to 2013 to determine
prevalence of known DM among first-generation Asian immigrants and whites. The
impact of various DM risk factors in Asian immigrants relative to whites was
analyzed and multivariable regression models were constructed to obtain adjusted
DM risk in Asian immigrants versus in whites.
RESULTS: Across the study span, we identified 2007 first-generation Asian
immigrants and 14 668 whites as having known DM or prediabetes mellitus (pre-DM).
From 2003 to 2013, the prevalence of DM and pre-DM combined rose from 6.8% to
12.4% in Asian immigrants and 5.5% to 6.9% in whites. Much of the increase could
be attributed to pre-DM, which rose from 0.7% to 3.2% in Asian immigrants during
the study period. The impacts of age and body mass index on DM risk were
consistently greater in Asian immigrants than in whites. Non-DM Asian immigrants
were found less likely to engage in physical activity than were non-DM whites.
After adjustment of various associated factors, Asian immigrants were more likely
than whites to have DM and this relative risk for DM gradually increased across
the study period.
CONCLUSIONS: A rising prevalence of known DM and particularly pre-DM among Asian
immigrants in California was observed during the previous decade. To reduce the
burden of diabetes and its complications, future strategies should consider
specific risk factors for this ethnic group, including encouraging physical
activity.
DOI: 10.1136/bmjdrc-2016-000327
PMCID: PMC5278214
PMID: 28176974
Conflict of interest statement: Conflicts of Interest: None declared.
45. Mol Cell Proteomics. 2018 Jan;17(1):95-110. doi: 10.1074/mcp.RA117.000217. Epub
2017 Nov 7.
Characterization of the Molecular Mechanisms Underlying Glucose Stimulated
Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational
Modification Specific Proteomics (PTMomics).
Kang T(1), Jensen P(1), Huang H(1), Lund Christensen G(2), Billestrup N(2),
Larsen MR(3).
Author information:
(1)From the ‡Department of Biochemistry and Molecular Biology, PR group,
University of Southern Denmark, Odense, Denmark.
(2)§Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen
N, Denmark.
(3)From the ‡Department of Biochemistry and Molecular Biology, PR group,
University of Southern Denmark, Odense, Denmark; mrl@bmb.sdu.dk.
Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to
elevated blood glucose levels, in order to maintain an adequate control of energy
balance and glucose homeostasis. However, the molecular mechanisms underlying the
insulin secretion are unclear. Improving our understanding of glucose-stimulated
insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for
developing better interventions against diabetes. Here, we aimed at identifying
novel signaling pathways involved in the initial release of insulin from PBCs
after glucose stimulation using quantitative strategies for the assessment of
phosphorylated proteins and sialylated N-linked (SA) glycoproteins.Islets of
Langerhans derived from newborn rats with a subsequent 9-10 days of maturation in
vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and
15 min. The isolated islets were subjected to time-resolved quantitative
phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of
phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS.
Using bioinformatics we analyzed the functional signaling pathways during GSIS,
including well-known insulin secretion pathways. Furthermore, we identified six
novel activated signaling pathways (e.g. agrin interactions and prolactin
signaling) at 15 min GSIS, which may increase our understanding of the molecular
mechanism underlying GSIS. Moreover, we validated some of the regulated
phosphosites by parallel reaction monitoring, which resulted in the validation of
eleven new phosphosites significantly regulated on GSIS. Besides protein
phosphorylation, alteration in SA glycosylation was observed on several surface
proteins on brief GSIS. Interestingly, proteins important for cell-cell
interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g.
integrins, semaphorins, and plexins) were found regulated at the level of
sialylation, but not in protein expression. Collectively, we believe that this
comprehensive Proteomics and PTMomics survey of signaling pathways taking place
during brief GSIS of primary PBCs is contributing to understanding the complex
signaling underlying GSIS.
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI: 10.1074/mcp.RA117.000217
PMID: 29113996
46. J Diabetes Sci Technol. 2017 Mar;11(2):278-283. doi: 10.1177/1932296816663745.
Epub 2016 Sep 25.
Clinical and Laboratory Evaluation of a New Specific Point-of-Care Test for

Intact Proinsulin.
Pfützner A(1)(2)(3)(4), Pfützner AH(3), Kann PH(5), Burgard G(4).
Author information:
(1)1 Pfützner Science & Health Institute, Mainz, Germany.
(2)2 University of Applied Science, Bingen, Germany.
(3)3 Sciema UG, Mainz, Germany.
(4)4 Insulin NG LLC, Naples, FL, USA.
(5)5 University Hospital Marburg, Department of Endocrinology and Diabetes,
Marburg, Germany.
BACKGROUND: Intact proinsulin is a biomarker for pancreatic ß-cell dysfunction.
In large prospective studies in nondiabetic subjects, elevated intact proinsulin
predicted development of type 2 diabetes and/or macrovascular events up to 7
years in advance. This study was performed to evaluate a new semiquantitative
lateral flow-based point-of-care rapid test (POCT) for elevated intact proinsulin
(cutoff: 15 pmol/L). The test requires 10 µL of capillary whole blood, with
visual readout after 5 minutes. It is best applied at 2 hours after a glucose
challenge or a meal.
METHODS: POCT results were obtained by health care professionals from 60 patients
and healthy subject (33 female, 27 male, 28 type 2 diabetes, age: 53.6 ± 12.3
years). An additional venous blood sample was obtained from all participants for
measurement of intact proinsulin by means of a quantitative ELISA reference
method (TecoMedical, Sissach, Switzerland).
RESULTS: Elevated intact proinsulin levels (>15 pmol/L) were determined by the
reference method in 26 participants, of whom 22 were also positive with the POCT
(sensitivity: 85%). All 34 subjects with low intact proinsulin levels were tested
negative by the POCT (specificity: 100%).
CONCLUSIONS: The test successfully detected elevated postprandial intact
proinsulin levels in 85% of the tested subjects and no false positive test result
occurred. This POCT can therefore serve as a simple screening tool for
identification of patients with prevalent ß-cell dysfunction, who are at high
risk for development of type 2 diabetes and/or macrovascular events within the
next 5-7 years.
DOI: 10.1177/1932296816663745
PMCID: PMC5478019
47. J Diabetes Res. 2017;2017:2657820. doi: 10.1155/2017/2657820. Epub 2017 Dec 3.
A Clinical Mentorship and Quality Improvement Program to Support Health Center
Nurses Manage Type 2 Diabetes in Rural Rwanda.
Ndayisaba A(1), Harerimana E(2), Borg R(1), Miller AC(3), Kirk CM(1), Hann K(4),
Hirschhorn LR(5), Manzi A(6), Ngoga G(1), Dusabeyezu S(1), Mutumbira C(2), Mpunga
T(2), Ngamije P(2), Nkikabahizi F(2), Mubiligi J(1), Niyonsenga SP(2), Bavuma
C(2)(7), Park PH(1).
Author information:
(1)Partners in Health/Inshuti Mu Buzima, Kigali, Rwanda.
(2)Ministry of Health, Kigali, Rwanda.
(3)Harvard Medical School, Boston, MA, USA.
(4)Partners in Health, Freetown, Sierra Leone.
(5)Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
(6)Partners in Health, Boston, MA, USA.
(7)University of Rwanda College of Medicine and Health Sciences, Kigali, Rwanda.
Introduction: The prevalence of diabetes mellitus is rapidly rising in SSA.
Interventions are needed to support the decentralization of services to improve

and expand access to care. We describe a clinical mentorship and quality
improvement program that connected nurse mentors with nurse mentees to support
the decentralization of type 2 diabetes care in rural Rwanda.
Methods: This is a descriptive study. Routinely collected data from patients with
type 2 diabetes cared for at rural health center NCD clinics between January 1,
2013 and December 31, 2015, were extracted from EMR system. Data collected as
part of the clinical mentorship program were extracted from an electronic
database. Summary statistics are reported.
Results: The patient population reflects the rural settings, with low rates of
traditional NCD risk factors: 5.6% of patients were current smokers, 11.0% were
current consumers of alcohol, and 11.9% were obese. Of 263 observed nurse
mentee-patient encounters, mentor and mentee agreed on diagnosis 94.4% of the
time. Similarly, agreement levels were high for medication, laboratory exam, and
follow-up plans, at 86.3%, 87.1%, and 92.4%, respectively.
Conclusion: Nurses that receive mentorship can adhere to a type 2 diabetes
treatment protocol in rural Rwanda primary health care settings.
DOI: 10.1155/2017/2657820
PMCID: PMC5738565
48. J Tradit Complement Med. 2017 Jun 12;8(1):178-183. doi:
10.1016/j.jtcme.2017.05.010. eCollection 2018 Jan.
Co-administration effects of aqueous extract of turnip leaf and metformin in
diabetic rats.
Hassanzadeh-Taheri M(1), Hassanpour-Fard M(2), Doostabadi M(1), Moodi H(1),
Vazifeshenas-Darmiyan K(3), Hosseini M(4).

Author information:
(1)Department of Anatomy, Faculty of Medicine, Birjand University of Medical
Sciences, Birjand, Iran.
(2)Department of Pharmacology, Faculty of Medicine, Berberis & Jujube Research
Center, Birjand University of Medical Sciences, Birjand, Iran.
(3)Department of Clinical Biochemistry, Faculty of Medicine, Birjand University
of Medical Sciences, Birjand, Iran.
(4)Cellular and Molecular Research Center, Birjand University of Medical
Sciences, Birjand, Iran.
Background: There is a variety of experimentally proven medicinal plants having
antidiabetic properties but data on herb-drug interaction are very limited.
Earlier studies indicated that aqueous extract of turnip leaf (AETL) has
hypoglycemic potential in diabetic animals. The present study was conducted to
evaluate co-administration effects of AETL and metformin, a commonly used
antidiabetic drug, in diabetic rats.
Methods: Metformin at the two different doses (50,100 mg/kg) and AETL at the dose
of 400 mg/kg (separately or concurrent with metformin) were orally given to
streptozotocin-induced diabetic rats for 4 weeks daily. Fasting blood glucose
(FBG) was measured at the times 0, 7, 14, 21 and 28 days after investigation. At
the end of study, liver enzymes activity [aspartate aminotransferase (AST) and
alanine aminotransferase (ALT)] as well as liver histopathology were evaluated.
Results: Both treatments could significantly decrease FBG levels when they
administrated separately. Interestingly, co-administration of AETL and metformin
in a dose dependent manner significantly improved hypoglycemic activity of
metformin. While neither metformin nor AETL could ameliorate liver alterations
alone, but in concomitant therapy they efficiently attenuated liver enzymes
elevation and histological damages.
Conclusion: The results of the present study demonstrate that combination of
metformin with AETL enhance the prior effectiveness and reduced the latter
adverse effects by a synergistic interaction.

DOI: 10.1016/j.jtcme.2017.05.010
PMCID: PMC5756016
PMID: 29322007
49. J Tissue Eng. 2017 Oct 30;8:2041731417738145. doi: 10.1177/2041731417738145.
eCollection 2017 Jan-Dec.
Cold-perfusion decellularization of whole-organ porcine pancreas supports human
fetal pancreatic cell attachment and expression of endocrine and exocrine
markers.
Elebring E(1), Kuna VK(1), Kvarnström N(2), Sumitran-Holgersson S(1).
Author information:
(1)Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy,
University of Gothenburg, Gothenburg, Sweden.
(2)The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
Despite progress in the field of decellularization and recellularization, the
outcome for pancreas has not been adequate. This might be due to the challenging
dual nature of pancreas with both endocrine and exocrine tissues. We aimed to
develop a novel and efficient cold-perfusion method for decellularization of
porcine pancreas and recellularize acellular scaffolds with human fetal
pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with
sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular
material, while preserving the extracellular matrix structure. Furthermore,
recellularization of acellular pieces with human fetal pancreatic stem cells for
14 days showed attached and proliferating cells. Both endocrine (C-peptide and
PDX1) and exocrine (glucagon and α-amylase) markers were expressed in

recellularized tissues. Thus, cold-perfusion can successfully decellularize
porcine pancreas, which when recellularized with human fetal pancreatic stem
cells shows relevant endocrine and exocrine phenotypes. Decellularized pancreas
is a promising biomaterial and might translate to clinical relevance for
treatment of diabetes.
DOI: 10.1177/2041731417738145
PMCID: PMC5669317
PMID: 29118967
Conflict of interest statement: Declaration of conflicting interests: The
author(s) declared the following potential conflicts of interest with respect to
the research, authorship, and/or publication of this article: S.S.H. holds shares
in NovaHep AB, a biotechnology company in the field of regenerative medicine. The
others have no conflicts of interest.
50. BMC Psychiatry. 2018 Aug 2;18(1):249. doi: 10.1186/s12888-018-1826-4.
Combination therapy as a potential risk factor for the development of type 2
diabetes in patients with schizophrenia: the GOMAP study.
Mamakou V(1)(2), Hackinger S(3), Zengini E(4)(5), Tsompanaki E(6), Marouli E(7),
Serafetinidis I(8), Prins B(3), Karabela A(9), Glezou E(4), Southam L(3)(10),
Rayner NW(3)(10)(11), Kuchenbaecker K(3), Lamnissou K(12), Kontaxakis V(13),
Dedoussis G(14), Gonidakis F(15), Thanopoulou A(16), Tentolouris N(17), Zeggini
E(3).
Author information:
(1)Medical School, National and Kapodistrian University Athens, 75 M. Assias
Street, 115 27, Athens, Greece. vmamakou@hotmail.com.

(2)Dromokaiteio Psychiatric Hospital, 124 61, Athens, Greece.
vmamakou@hotmail.com.
(3)Wellcome Sanger Institute, Hinxton, Cambridge, HH, CB10 1, UK.
(4)Dromokaiteio Psychiatric Hospital, 124 61, Athens, Greece.
(5)Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
(6)School of Information Sciences and Technology, Department of Statistics,
Athens University of Economics and Business, 10434, Athens, Greece.
(7)William Harvey Research Institute, Barts and The London School of Medicine and
Dentistry, Queen Mary University of London, EC1M 6BQ, London, UK.
(8)Department of Gastroenterology, Gennimatas General Hospital, 11527, Athens,
Greece.
(9)Dafni Psychiatric Hospital, 12462, Athens, Greece.
(10)Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
(11)Oxford Centre for Diabetes Endocrinology and Metabolism, Oxford, UK.
(12)National and Kapodistrian University of Athens, Department of Biology,
Athens, Panepistimioupolis, AnoIlisia, 15771, Athens, Greece.
(13)Early Psychosis Unit, 1st Department of Psychiatry, Eginition Hospital,
Medical School, National and Kapodistrian University of Athens, 11527, Athens,
Greece.
(14)Department of Nutrition-Dietetics, Harokopio University, 17671, Athens,
Greece.
(15)1st Psychiatric Department, Eginition Hospital, Medical School, National and
Kapodistrian University of Athens, 11527, Athens, Greece.
(16)Diabetes Centre, 2nd Department of Internal Medicine, Hippokration General
Hospital, Medical School, National and Kapodistrian University of Athens, 11527,
Athens, Greece.
(17)First Department of Propaedeutic Internal Medicine, National and Kapodistrian
University of Athens, Medical School, Laiko General Hospital, 11527, Athens,
Greece.
BACKGROUND: Schizophrenia (SCZ) is associated with increased risk of type 2

diabetes (T2D). The potential diabetogenic effect of concomitant application of
psychotropic treatment classes in patients with SCZ has not yet been evaluated.
The overarching goal of the Genetic Overlap between Metabolic and Psychiatric
disease (GOMAP) study is to assess the effect of pharmacological, anthropometric,
lifestyle and clinical measurements, helping elucidate the mechanisms underlying
the aetiology of T2D.
METHODS: The GOMAP case-control study (Genetic Overlap between Metabolic and
Psychiatric disease) includes hospitalized patients with SCZ, some of whom have
T2D. We enrolled 1653 patients with SCZ; 611 with T2D and 1042 patients without
T2D. This is the first study of SCZ and T2D comorbidity at this scale in the
Greek population. We retrieved detailed information on first- and
second-generation antipsychotics (FGA, SGA), antidepressants and mood
stabilizers, applied as monotherapy, 2-drug combination, or as 3- or more drug
combination. We assessed the effects of psychotropic medication, body mass index,
duration of schizophrenia, number of hospitalizations and physical activity on
risk of T2D. Using logistic regression, we calculated crude and adjusted odds
ratios (OR) to identify associations between demographic factors and the
psychiatric medications.
RESULTS: Patients with SCZ on a combination of at least three different classes
of psychiatric drugs had a higher risk of T2D [OR 1.81 (95% CI 1.22-2.69);
p = 0.003] compared to FGA alone therapy, after adjustment for age, BMI, sex,
duration of SCZ and number of hospitalizations. We did not find evidence for an
association of SGA use or the combination of drugs belonging to two different
classes of psychiatric medications with increased risk of T2D [1.27 (0.84-1.93),
p = 0.259 and 0.98 (0.71-1.35), p = 0.885, respectively] compared to FGA use.
CONCLUSIONS: We find an increased risk of T2D in patients with SCZ who take a
combination of at least three different psychotropic medication classes compared
to patients whose medication consists only of one or two classes of drugs.
DOI: 10.1186/s12888-018-1826-4
PMCID: PMC6090901
PMID: 30071838
51. Microarrays (Basel). 2016 Aug 10;5(3). pii: E21. doi: 10.3390/microarrays5030021.
A Combinatorial Protein Microarray for Probing Materials Interaction with
Pancreatic Islet Cell Populations.
Delalat B(1), Rojas-Canales DM(2)(3), Rasi Ghaemi S(4), Waibel M(5), Harding
FJ(6), Penko D(7)(8)(9), Drogemuller CJ(10)(11)(12), Loudovaris T(13), Coates
PT(14)(15)(16), Voelcker NH(17).
Author information:
(1)Australian Research Council Centre of Excellence in Convergent Bio-Nano
Science and Technology, Future Industries Institute, University of South
Australia, Adelaide 5095 SA, Australia. Bahman.Delalat@unisa.edu.au.
(2)School of Medicine, University of Adelaide, Adelaide5005 SA, Australia.
Darling.Rojas@sa.gov.au.
(3)Centre for Clinical and Experimental Transplantation, Adelaide 5000 SA,
Australia. Darling.Rojas@sa.gov.au.
Australia, Adelaide 5095 SA, Australia. rasighaemis@yahoo.com.
(5)Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research,
Fitzroy 3065 Vic, Australia. mwaibel@svi.edu.au.
Australia, Adelaide 5095 SA, Australia. Fran.Harding@unisa.edu.au.
Daniella.Penko@sa.gov.au.

Australia. Daniella.Penko@sa.gov.au.
(9)Central Northern Adelaide Renal Transplantation Service, Royal Adelaide
Hospital, Adelaide 5000 SA, Australia. Daniella.Penko@sa.gov.au.
Chris.Drogemuller@sa.gov.au.
Australia. Chris.Drogemuller@sa.gov.au.
Hospital, Adelaide 5000 SA, Australia. Chris.Drogemuller@sa.gov.au.
(13)Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research,
Fitzroy 3065 Vic, Australia. tloudovaris@svi.edu.au.
Toby.Coates@sa.gov.au.
Australia. Toby.Coates@sa.gov.au.
Hospital, Adelaide 5000 SA, Australia. Toby.Coates@sa.gov.au.
Australia, Adelaide 5095 SA, Australia. Nico.Voelcker@unisa.edu.au.
Pancreatic islet transplantation has become a recognized therapy for
insulin-dependent diabetes mellitus. During isolation from pancreatic tissue, the
islet microenvironment is disrupted. The extracellular matrix (ECM) within this
space not only provides structural support, but also actively signals to regulate
islet survival and function. In addition, the ECM is responsible for growth
factor presentation and sequestration. By designing biomaterials that recapture
elements of the native islet environment, losses in islet function and number can
potentially be reduced. Cell microarrays are a high throughput screening tool
able to recreate a multitude of cellular niches on a single chip. Here, we
present a screening methodology for identifying components that might promote

islet survival. Automated fluorescence microscopy is used to rapidly identify
islet derived cell interaction with ECM proteins and immobilized growth factors
printed on arrays. MIN6 mouse insulinoma cells, mouse islets and, finally, human
islets are progressively screened. We demonstrate the capability of the platform
to identify ECM and growth factor protein candidates that support islet viability
and function and reveal synergies in cell response.
DOI: 10.3390/microarrays5030021
PMCID: PMC5040968
PMID: 27600088
Conflict of interest statement: The authors have declared that no competing
interests exist.
52. Clin Epidemiol. 2017 Jan 25;9:63-65. doi: 10.2147/CLEP.S130096. eCollection 2017.
Comment on "An algorithm for identification and classification of individuals
with type 1 and type 2 diabetes mellitus in a large primary care database",
written by Sharma et al.
Bocquet V(1).
Author information:
(1)Competence Center for Methodology and Statistics, Luxembourg Institute of
Health, Luxembourg.
DOI: 10.2147/CLEP.S130096
PMCID: PMC5279818
PMID: 28182137
Conflict of interest statement: The author reports no conflicts of interest in
this communication.
53. Evid Based Complement Alternat Med. 2018 Sep 13;2018:3248521. doi:
10.1155/2018/3248521. eCollection 2018.
Comparative Proteomic Analysis of Two Differently Extracted Coptis chinensis in
the Treatment of Type 2 Diabetic Rats.
Qiu X(1), Wei X(2), Guan H(1), Su H(1), Gong J(1), Fang K(3), Zou X(1), Dong
H(1), Xu L(1), Lu F(1).
Author information:
Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430030, China.
(2)Accounting Department, Lowa State University, Lowa State 50011, USA.
(3)Department of Integrated Traditional Chinese and Western Medicine, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430030, China.
Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese
medicine due to its significant hypoglycemic and hypolipidemic effects. It was
reported that CC powders are more effective than CC decoctions. In this study, a
rat model of type 2 diabetes was established and treated with
supercritical-extracted CC and gastric juice extracted CC, respectively. Body
weight, fasting plasma insulin, insulin resistance index, and lipid profiles were
measured along with oral glucose tolerance tests (OGTTs). In addition, the levels
of plasma proteins were compared between type 2 diabetic rats and CC-treated rats
using an iTRAQ-based quantitative proteomic analysis. The results showed that the
plasma levels of triglyceride (TC), total cholesterol (TG), and low-density
lipoprotein (LDL) in rats of both CC-treated groups were significantly decreased.
In addition, the proteomic analysis identified 929 proteins, while 15 proteins
were selected from these 929 proteins based on their expression levels and
bioinformatic results. Among these 15 proteins, 9 proteins (IGF-1, Igfbp4,
Igfbp-6, Igfals, C2, C4, Cfi, Prdx-2, and Prdx-3) were upregulated in the two
CC-treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC-1, ApoC-3, ApoB-100,
and ApoE) were downregulated. The functions of these proteins are associated with
glucose metabolism, insulin action, immunity, inflammation, lipid metabolism,
oxidation, and antioxidation. The two differently extracted CC did not show
significant differences in terms of their treatment efficacy. This research
expanded our understanding on the therapeutic effects and mechanisms of CC in the
treatment of type 2 diabetes.
DOI: 10.1155/2018/3248521
PMCID: PMC6158947
PMID: 30302116
54. PLoS One. 2017 Jul 5;12(7):e0179238. doi: 10.1371/journal.pone.0179238.
eCollection 2017.
Comparing distributions of polygenic risk scores of type 2 diabetes and coronary
heart disease within different populations.
Reisberg S(1)(2)(3), Iljasenko T(1), Läll K(4)(5), Fischer K(5), Vilo J(1)(2)(3).
Author information:
(1)University of Tartu, Institute of Computer Science, Tartu, Estonia.
(2)Software Technology and Applications Competence Centre, Tartu, Estonia.
(3)Quretec Ltd, Tartu, Estonia.

(4)University of Tartu, Institute of Mathematics and Statistics, Tartu, Estonia.
(5)Estonian Genome Centre, University of Tartu, Tartu, Estonia.
Polygenic risk scores are gaining more and more attention for estimating genetic
risks for liabilities, especially for noncommunicable diseases. They are now
calculated using thousands of DNA markers. In this paper, we compare the score
distributions of two previously published very large risk score models within
different populations. We show that the risk score model together with its risk
stratification thresholds, built upon the data of one population, cannot be
applied to another population without taking into account the target population's
structure. We also show that if an individual is classified to the wrong
population, his/her disease risk can be systematically incorrectly estimated.
PMCID: PMC5497939
55. Int J Equity Health. 2018 Jun 15;17(1):82. doi: 10.1186/s12939-018-0796-y.
Comparing the income-related inequity of tested prevalence and self-reported
prevalence of hypertension in China.
Su M(1), Si Y(1), Zhou Z(2), Shen C(1), Dong W(3), Fan X(3), Wang X(4), Wei X(5).
Author information:
(1)School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an,
China.
(2)School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an,
China. zzliang1981@163.com.
(3)School of Public Health, Xi'an Jiaotong University, Xi'an, China.

(4)International Business School Suzhou, Xi'an Jiaotong-Liverpool University,
Suzhou, China.
(5)Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
xiaolin.wei@utoronto.ca.
BACKGROUND: Hypertension has become a global health challenge given its high
prevalence and but low awareness and detection. Whether the actual prevalence of
hypertension has been estimated is important, especially for the poor. This study
aimed to measure tested prevalence and self-reported prevalence of hypertension
and compare the inequity between them in China.
METHODS: Data were derived from China Health and Nutrition Survey (CHNS)
conducted in 2011. By using the multistage, stratified, random sampling method,
12,168 respondents aged 18 or older were identified for analysis. Both tested
prevalence (systolic blood pressure ≥ 140 mmHg or/and diastolic blood
pressure ≥ 90 mmHg or /and current use any of antihypertensive medication) and
self-reported prevalence (ever diagnosed with hypertension by a doctor) were used
to measure the prevalence of hypertension. The concentration index was employed
to measure the extent of inequality in tested prevalence and self-reported
prevalence. A decomposition method, based on a Probit model, was used to analyze
income-related horizontal inequity of tested prevalence and self-reported
prevalence.
RESULTS: The tested prevalence and self-reported prevalence of total respondents
were 28.8% [95% CI (28.0%, 29.6%)] and 15.7% [95% CI (15.0%, 16.3%)], and 26.4%
[95% CI (25.1%, 27.6%)] and 19.0% [95% CI (17.9%, 20.1%)] in urban areas, and
30.3% [95% CI (29.3%, 31.4%)] and 13.5% [95% CI (12.7%, 14.3%)] in rural areas.
The horizontal inequity indexes of mean tested prevalence and self-reported
prevalence were - 0.0494 and 0.1203 of total respondents, - 0.0736 and 0.0748 in
urban area, and - 0.0177 and 0.0466 in rural area respectively, indicating
pro-poor inequity in tested prevalence and pro-rich inequity in self-reported
prevalence of hypertension. Economic status, education attainment and age were
key factors of the pro-poor inequity in tested prevalence. Economic status, area
and age were key factors to explain the poor-rich inequity in self-reported
prevalence.
CONCLUSIONS: This study revealed self-reported prevalence of hypertension was
much lower than tested prevalence in China, while a larger gap between
self-reported and tested prevalence was found in rural areas. Our study suggested
social strategies aiming at narrowing economic gap and regional disparities,
reducing educational inequity, and facilitating health conditions of the elderly
should be implemented. Finally, awareness raising campaigns to test hypertension
in rural area need be strengthened by health education programs and improving the
access to public health service, especially for those who do not engage with
regular health checkups.
DOI: 10.1186/s12939-018-0796-y
PMCID: PMC6003002
PMID: 29907150
eCollection 2017.
Comparison of spectral-domain optical coherence tomography for intra-retinal
layers thickness measurements between healthy and diabetic eyes among Chinese
adults.
Li ST(1), Wang XN(1), Du XH(1), Wu Q(1)(2).
Author information:
(1)Department of Ophthalmology, Shanghai Jiaotong University Affiliated Sixth
People's Hospital, Shanghai, China.

PURPOSE: To compare intra-retinal layer thickness measurements between eyes with
no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis
spectral-domain optical coherence tomography (SD-OCT).
METHODS: Cross-sectional observational analysis study. High-resolution macular
volume scans (30° * 25°) were obtained for 133 type 2 diabetes mellitus (T2DM)
patients with no DR, 42 T2DM patients with mild DR and 115 healthy controls. The
mean thickness was measured in all 9 Early Treatment Diabetic Retinopathy Study
(ETDRS) sectors for 8 separate layers, inner retinal layer (IRL), outer retinal
layer (ORL) and total retina (TR), after automated segmentation. The ETDRS grid
consisted of three concentric circles of 1-, 3-, and 6-mm diameter. The superior,
inferior, temporal, and nasal sectors of the 3- and 6-mm circles were
respectively designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear
regression analyses were conducted to evaluate the associations between the
intra-retinal layer thicknesses, age, diabetes duration, fasting blood glucose
and HbA1c.
RESULTS: The mean age and duration of T2DM were 61.1 and 13.7 years,
respectively. Although no significant differences in the average TR and ORL
volumes were observed among the groups, significant differences were found in the
volume and sectorial thicknesses of the inner plexiform layer (IPL), outer
plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of
the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in
the no-DR group compared with the controls (P < 0.05). The thickness of the OPL
(S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P <
0.05). The average IPL thickness was significantly negatively correlated with age
and the duration of diabetes.
CONCLUSION: The assessment of the intra-retinal layer thickness showed a
significant decrease in the IPL and IRL thicknesses in Chinese adults with T2DM,
even in the absence of visible microvascular signs of DR.
PMCID: PMC5426752
57. Int J Mol Sci. 2017 Sep 21;18(10). pii: E2010. doi: 10.3390/ijms18102010.
A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2
Diabetes.
Du Z(1)(2), Uversky VN(3)(4)(5).
Author information:
(1)Department of Molecular Medicine, Morsani College of Medicine, University of
South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA.
duzh@szu.edu.cn.
(2)Department of Computer Science, College of Computer Science and Software,
Shenzhen University, Shenzhen 518060, China. duzh@szu.edu.cn.
(3)Department of Molecular Medicine, Morsani College of Medicine, University of
South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA.
vuversky@health.usf.edu.
(4)USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine,
University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620,
USA. vuversky@health.usf.edu.
(5)Laboratory of New Methods in Biology, Institute for Biological
Instrumentation, Russian Academy of Sciences, Institutskaya str., 7, Pushchino,
Moscow 142290, Russia. vuversky@health.usf.edu.
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is
strongly associated with hyperglycemia (high blood sugar) related to either
insulin resistance or insufficient insulin production. Among the various
molecular events and players implicated in the manifestation and development of
diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia
of Genes and Genomes (KEGG) database has information on 34 human proteins
experimentally shown to be related to the T2DM pathogenesis. It is known that
many proteins associated with different human maladies are intrinsically
disordered as a whole, or contain intrinsically disordered regions. The presented
study shows that T2DM is not an exception to this rule, and many proteins known
to be associated with pathogenesis of this malady are intrinsically disordered.
The multiparametric bioinformatics analysis utilizing several computational tools
for the intrinsic disorder characterization revealed that IRS1, IRS2, IRS4, MAFA,
PDX1, ADIPO, PIK3R2, PIK3R5, SoCS1, and SoCS3 are expected to be highly
disordered, whereas VDCC, SoCS2, SoCS4, JNK9, PRKCZ, PRKCE, insulin, GCK, JNK8,
JNK10, PYK, INSR, TNF-α, MAPK3, and Kir6.2 are classified as moderately
disordered proteins, and GLUT2, GLUT4, mTOR, SUR1, MAPK1, IKKA, PRKCD, PIK3CB,
and PIK3CA are predicted as mostly ordered. More focused computational analyses
and intensive literature mining were conducted for a set of highly disordered
proteins related to T2DM. The resulting work represents a comprehensive survey
describing the major biological functions of these proteins and functional roles
of their intrinsically disordered regions, which are frequently engaged in
protein-protein interactions, and contain sites of various posttranslational
modifications (PTMs). It is also shown that intrinsic disorder-associated PTMs
may play important roles in controlling the functions of these proteins.
Consideration of the T2DM proteins from the perspective of intrinsic disorder
provides useful information that can potentially lead to future experimental
studies that may uncover latent and novel pathways associated with the disease.
DOI: 10.3390/ijms18102010
PMCID: PMC5666700
Conflict of interest statement: The authors declare no conflict of interest.

58. Ther Clin Risk Manag. 2018 Mar 13;14:511-521. doi: 10.2147/TCRM.S150638.
eCollection 2018.
Continuity of care with physicians and risk of subsequent hospitalization and
end-stage renal disease in newly diagnosed type 2 diabetes mellitus patients.
Chang PY(1), Chien LN(2), Bai CH(1), Lin YF(3), Chiou HY(1).
Author information:
(1)School of Public Health, College of Public Health, Taipei Medical University,
Taipei, Taiwan.
(2)School of Health Care Administration, Taipei Medical University, Taipei,
Taiwan.
(3)Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei,
Taiwan.
Purpose: Effective management for type 2 diabetes mellitus (DM) can slow the
progression of kidney outcomes and reduce hospital admissions. Better continuity
of care (COC) was found to improve patients' adherence and self-management. This
study examined the associations between COC, hospitalization, and end-stage renal
disease (ESRD) in DM patients.
Patients and methods: In the cohort study, data from 1996 to 2012 were retrieved
from the Longitudinal Health Insurance Database, using inverse probability
weighted analysis. A total of 26,063 patients with newly diagnosed type 2 DM who
had been treated with antihyperglycemic agents were included. COC is to assess
the extent to which a DM patient visited the same physician during the study
period. This study categorized COC into 3 groups - low, intermediate, and high, -
according to the distribution of scores in our sample.
Results: The number of ESRD patients in the high, intermediate, and low COC
groups were 92 (22.33%), 130 (31.55%), and 190 (46.12%), respectively, and the
mean follow-up periods for the 3 groups were 7.13, 7.12, and 7.27 years,
respectively. After using inverse probability weighting, the intermediate and low
COC groups were significantly associated with an increased risk of ESRD compared
with the high COC group (adjusted hazard ratio (aHR) 1.36 [95% CI, 1.03-1.80] and
aHR 1.76 [95% CI, 1.35-2.30], respectively). The intermediate and low COC groups
were also significantly associated with the subsequent hospitalization compared
with the high COC group (aHR 1.15 [95% CI, 0.99-1.33] and aHR 1.72 [95% CI,
1.50-1.97], respectively).
Conclusion: COC is related to ESRD onset and subsequent hospitalization among
patients with DM. This study suggested that when DM patients keep visiting the
same physician for managing their diseases, the progression of renal disease can
be prevented.
DOI: 10.2147/TCRM.S150638
PMCID: PMC5856058
PMID: 29559787
Conflict of interest statement: Disclosure The authors report no conflicts of
interest in this work.
59. Biosensors (Basel). 2018 Apr 25;8(2). pii: E43. doi: 10.3390/bios8020043.
Continuous Glucose Monitoring in Resource-Constrained Settings for Hypoglycaemia
Detection: Looking at the Problem from the Other Side of the Coin.
Bila R(1), Varo R(2)(3), Madrid L(4)(5), Sitoe A(6), Bassat Q(7)(8)(9)(10).
Author information:
(1)Centro de Investigação em Saúde de Manhiça (CISM), CP1929 Maputo, Mozambique.
rubao.bila@manhica.net.

Rosauro.Varo@manhica.net.
(3)ISGlobal, Hospital Clínic-Universitat de Barcelona, 08036 Barcelona, Spain.
Rosauro.Varo@manhica.net.
lola.madrid@isglobal.org.
lola.madrid@isglobal.org.
antonio.sitoe@manhica.net.
quique.bassat@isglobal.org.
(9)Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys
23, 08010 Barcelona, Spain. quique.bassat@isglobal.org.
(10)Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan
de Déu (University of Barcelona), 08950 Barcelona, Spain.
The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices
has triggered a patient-centred revolution in the control and management of
diabetes mellitus and other metabolic conditions, improving the patient’s
glycaemic control and quality of life. Such devices, the use of which remains
typically restricted to high-income countries on account of their elevated costs,
at present show very limited implantation in resource-constrained settings, where
many other urgent health priorities beyond diabetes prevention and management
still need to be resolved. In this commentary, we argue that such devices could
have an additional utility in low-income settings, whereby they could be
selectively used among severely ill children admitted to hospital for closer
monitoring of paediatric hypoglycaemia, a life-threatening condition often
complicating severe cases of malaria, malnutrition, and other common paediatric

conditions.
DOI: 10.3390/bios8020043
PMCID: PMC6023081
60. Int J Epidemiol. 2018 Mar 19. doi: 10.1093/ije/dyy016. [Epub ahead of print]
Contributions of mean and shape of blood pressure distribution to worldwide
trends and variations in raised blood pressure: a pooled analysis of 1018
population-based measurement studies with 88.6 million participants.
NCD Risk Factor Collaboration (NCD-RisC).
Collaborators: Zhou B, Bentham J, Di Cesare M, Bixby H, Danaei G, Hajifathalian
K, Taddei C, Carrillo-Larco RM, Djalalinia S, Khatibzadeh S, Lugero C, Peykari N,
Zhang WZ, Bennett J, Bilano V, Stevens GA, Cowan MJ, Riley LM, Chen Z, Hambleton
IR, Jackson RT, Kengne AP, Khang YH, Laxmaiah A, Liu J, Malekzadeh R, Neuhauser
HK, Sorić M, Starc G, Sundström J, Woodward M, Ezzati M, Abarca-Gómez L, Abdeen
ZA, Abu-Rmeileh NM, Acosta-Cazares B, Adams RJ, Aekplakorn W, Afsana K,
Aguilar-Salinas CA, Agyemang C, Ahmad NA, Ahmadvand A, Ahrens W, Ajlouni K,
Akhtaeva N, Al-Raddadi R, Ali MM, Ali O, Alkerwi A, Aly E, Amarapurkar DN,
Amouyel P, Amuzu A, Andersen LB, Anderssen SA, Ängquist LH, Anjana RM, Ansong D,
Aounallah-Skhiri H, Araújo J, Ariansen I, Aris T, Arlappa N, Arveiler D, Aryal
KK, Aspelund T, Assah FK, Assunção MCF, Avdicová M, Azevedo A, Azizi F, Babu BV,
Bahijri S, Balakrishna N, Bamoshmoosh M, Banach M, Bandosz P, Banegas JR,
Barbagallo CM, Barceló A, Barkat A, Barros AJD, Barros MV, Bata I, Batieha AM,
Batyrbek A, Baur LA, Beaglehole R, Romdhane HB, Benet M, Benson LS, Bernabe-Ortiz
A, Bernotiene G, Bettiol H, Bhagyalaxmi A, Bharadwaj S, Bhargava SK, Bi Y, Bikbov
M, Bista B, Bjerregaard P, Bjertness E, Bjertness MB, Björkelund C, Blokstra A,

Bo S, Bobak M, Boeing H, Boggia JG, Boissonnet CP, Bongard V, Borchini R, Bovet
P, Braeckman L, Brajkovich I, Branca F, Breckenkamp J, Brenner H, Brewster LM,
Bruno G, Bueno-de-Mesquita HBA, Bugge A, Burns C, Bursztyn M, de León AC,
Cacciottolo J, Cai H, Cameron C, Can G, Cândido APC, Capuano V, Cardoso VC,
Carlsson AC, Carvalho MJ, Casanueva FF, Casas JP, Caserta CA, Chamukuttan S, Chan
AW, Chan Q, Chaturvedi HK, Chaturvedi N, Chen CJ, Chen F, Chen H, Chen S, Chen Z,
Cheng CY, Dekkaki IC, Chetrit A, Chiolero A, Chiou ST, Chirita-Emandi A,
Chirlaque MD, Cho B, Cho Y, Christofaro DG, Chudek J, Cifkova R, Cinteza E,
Claessens F, Clays E, Concin H, Cooper C, Cooper R, Coppinger TC, Costanzo S,
Cottel D, Cowell C, Craig CL, Crujeiras AB, Cruz JJ, D'Arrigo G, d'Orsi E,
Dallongeville J, Damasceno A, Danaei G, Dankner R, Dantoft TM, Dauchet L,
Davletov K, De Backer G, De Bacquer D, de Gaetano G, De Henauw S, de Oliveira PD,
De Smedt D, Deepa M, Dehghan A, Delisle H, Deschamps V, Dhana K, Di Castelnuovo
AF, Dias-da-Costa JS, Diaz A, Dickerson TT, Djalalinia S, Do HTP, Donfrancesco C,
Donoso SP, Döring A, Dorobantu M, Doua K, Drygas W, Dulskiene V, Džakula A,
Dzerve V, Dziankowska-Zaborszczyk E, Eggertsen R, Ekelund U, El Ati J, Elliott P,
Elosua R, Erasmus RT, Erem C, Eriksen L, Eriksson JG, Escobedo-de la Peña J,
Evans A, Faeh D, Fall CH, Farzadfar F, Felix-Redondo FJ, Ferguson TS, Fernandes
RA, Fernández-Bergés D, Ferrante D, Ferrari M, Ferreccio C, Ferrieres J, Finn JD,
Fischer K, Föger B, Foo LH, Forslund AS, Forsner M, Fouad HM, Francis DK, do
Carmo Franco M, Franco OH, Frontera G, Fuchs FD, Fuchs SC, Fujita Y, Furusawa T,
Gaciong Z, Galvano F, Garcia-de-la-Hera M, Gareta D, Garnett SP, Gaspoz JM,
Gasull M, Gates L, Geleijnse JM, Ghasemian A, Ghimire A, Giampaoli S, Gianfagna
F, Gill TK, Giovannelli J, Goldsmith RA, Gonçalves H, Gonzalez-Gross M,
González-Rivas JP, Gorbea MB, Gottrand F, Graff-Iversen S, Grafnetter D, Grajda
A, Grammatikopoulou MG, Gregor RD, Grodzicki T, Grøntved A, Grosso G, Gruden G,
Grujic V, Gu D, Guan OP, Gudmundsson EF, Gudnason V, Guerrero R, Guessous I,
Guimaraes AL, Gulliford MC, Gunnlaugsdottir J, Gunter M, Gupta PC, Gupta R,
Gureje O, Gurzkowska B, Gutierrez L, Gutzwiller F, Hadaegh F, Halkjær J,
Hambleton IR, Hardy R, Hari Kumar R, Hata J, Hayes AJ, He J, He Y, Elisabeth M,
Henriques A, Cadena LH, Herrala S, Heshmat R, Hihtaniemi IT, Ho SY, Ho SC, Hobbs
M, Hofman A, Dinc GH, Horimoto ARVR, Hormiga CM, Horta BL, Houti L, Howitt C,
Htay TT, Htet AS, Than Htike MM, Hu Y, Huerta JM, Huisman M, Husseini AS,
Huybrechts I, Hwalla N, Iacoviello L, Iannone AG, Ibrahim MM, Wong NI, Ikeda N,
Ikram MA, Irazola VE, Islam M, Al-Safi Ismail A, Ivkovic V, Iwasaki M, Jackson
RT, Jacobs JM, Jaddou H, Jafar T, Jamrozik K, Janszky I, Jasienska G, Jelaković
A, Jelaković B, Jennings G, Jeong SL, Jiang CQ, Joffres M, Johansson M,
Jokelainen JJ, Jonas JB, Jørgensen T, Joshi P, Jóźwiak J, Juolevi A, Jurak G,
Jureša V, Kaaks R, Kafatos A, Kajantie EO, Kalter-Leibovici O, Kamaruddin NA,
Karki KB, Kasaeian A, Katz J, Kauhanen J, Kaur P, Kavousi M, Kazakbaeva G, Keil
U, Boker LK, Keinänen-Kiukaanniemi S, Kelishadi R, Kemper HCG, Kengne AP,
Kerimkulova A, Kersting M, Key T, Khader YS, Khalili D, Khang YH, Khateeb M, Khaw
KT, Kiechl-Kohlendorfer U, Kiechl S, Killewo J, Kim J, Kim YY, Klumbiene J,
Knoflach M, Kolle E, Kolsteren P, Korrovits P, Koskinen S, Kouda K, Kowlessur S,
Koziel S, Kriemler S, Kristensen PL, Krokstad S, Kromhout D, Kruger HS, Kubinova
R, Kuciene R, Kuh D, Kujala UM, Kulaga Z, Krishna Kumar R, Kurjata P, Kusuma YS,
Kuulasmaa K, Kyobutungi C, Laatikainen T, Lachat C, Lam TH, Landrove O, Lanska V,
Lappas G, Larijani B, Laugsand LE, Laxmaiah A, Le Nguyen Bao K, Le TD, Leclercq
C, Lee J, Lee J, Lehtimäki T, León-Muñoz LM, Levitt NS, Li Y, Lilly CL, Lim WY,
Lima-Costa MF, Lin HH, Lin X, Lind L, Linneberg A, Lissner L, Litwin M, Liu J,
Lorbeer R, Lotufo PA, Lozano JE, Luksiene D, Lundqvist A, Lunet N, Lytsy P, Ma G,
Ma J, Machado-Coelho GLL, Machi S, Maggi S, Magliano DJ, Magriplis E, Majer M,
Makdisse M, Malekzadeh R, Malhotra R, Mallikharjuna Rao K, Malyutina S, Manios Y,
Mann JI, Manzato E, Margozzini P, Marques-Vidal P, Marques LP, Marrugat J,
Martorell R, Mathiesen EB, Matijasevich A, Matsha TE, Mbanya JCN, Mc Donald Posso
AJ, McFarlane SR, McGarvey ST, McLachlan S, McLean RM, McLean SB, McNulty BA,
Mediene-Benchekor S, Medzioniene J, Meirhaeghe A, Meisinger C, Menezes AMB, Menon
GR, Meshram II, Metspalu A, Meyer HE, Mi J, Mikkel K, Miller JC, Minderico CS,
Francisco J, Miranda JJ, Mirrakhimov E, Mišigoj-Durakovic M, Modesti PA, Mohamed
MK, Mohammad K, Mohammadifard N, Mohan V, Mohanna S, Mohd Yusoff MF, Møllehave
LT, Møller NC, Molnár D, Momenan A, Mondo CK, Monyeki KDK, Moon JS, Moreira LB,
Morejon A, Moreno LA, Morgan K, Moschonis G, Mossakowska M, Mostafa A, Mota J,

Esmaeel Motlagh M, Motta J, Msyamboza KP, Mu TT, Muiesan ML, Müller-Nurasyid M,
Murphy N, Mursu J, Musil V, Nabipour I, Nagel G, Naidu BM, Nakamura H, Námešná J,
Nang EEK, Nangia VB, Narake S, Nauck M, Navarrete-Muñoz EM, Ndiaye NC, Neal WA,
Nenko I, Neovius M, Nervi F, Neuhauser HK, Nguyen CT, Nguyen ND, Nguyen QN,
Nguyen QV, Nieto-Martínez RE, Niiranen TJ, Ning G, Ninomiya T, Nishtar S, Noale
M, Noboa OA, Noorbala AA, Norat T, Noto D, Al Nsour M, O'Reilly D, Oda E, Oehlers
G, Oh K, Ohara K, Olinto MTA, Oliveira IO, Omar MA, Onat A, Ong SK, Ono LM,
Ordunez P, Ornelas R, Osmond C, Ostojic SM, Ostovar A, Otero JA, Overvad K,
Owusu-Dabo E, Paccaud FM, Padez C, Pahomova E, Pajak A, Palli D, Palmieri L, Pan
WH, Panda-Jonas S, Panza F, Papandreou D, Park SW, Parnell WR, Parsaeian M, Patel
ND, Pecin I, Pednekar MS, Peer N, Peeters PH, Peixoto SV, Peltonen M, Pereira AC,
Peters A, Petersmann A, Petkeviciene J, Peykari N, Pham ST, Pigeot I, Pikhart H,
Pilav A, Pilotto L, Pitakaka F, Piwonska A, Plans-Rubió P, Polašek O, Porta M,
Portegies MLP, Pourshams A, Poustchi H, Pradeepa R, Prashant M, Price JF, Puder
JJ, Puiu M, Punab M, Qasrawi RF, Qorbani M, Bao TQ, Radic I, Radisauskas R,
Rahman M, Raitakari O, Raj M, Ramachandra Rao S, Ramachandran A, Ramos E, Rampal
L, Rampal S, Rangel Reina DA, Redon J, Reganit PFM, Ribeiro R, Riboli E, Rigo F,
Rinke de Wit TF, Ritti-Dias RM, Robinson SM, Robitaille C, Rodríguez-Artalejo F,
Del Cristo Rodriguez-Perez M, Rodríguez-Villamizar LA, Rojas-Martinez R,
Romaguera D, Ronkainen K, Rosengren A, Roy JGR, Rubinstein A, Sandra
Ruiz-Betancourt B, Rutkowski M, Sabanayagam C, Sachdev HS, Saidi O, Sakarya S,
Salanave B, Salazar Martinez E, Salmerón D, Salomaa V, Salonen JT, Salvetti M,
Sánchez-Abanto J, Sans S, Santos DA, Santos IS, Nunes Dos Santos R, Santos R,
Saramies JL, Sardinha LB, Sarganas G, Sarrafzadegan N, Saum KU, Savva S, Scazufca
M, Schargrodsky H, Schipf S, Schmidt CO, Schöttker B, Schultsz C, Schutte AE,
Sein AA, Sen A, Senbanjo IO, Sepanlou SG, Sharma SK, Shaw JE, Shibuya K, Shin DW,
Shin Y, Si-Ramlee K, Siantar R, Sibai AM, Santos Silva DA, Simon M, Simons J,
Simons LA, Sjöström M, Skovbjerg S, Slowikowska-Hilczer J, Slusarczyk P, Smeeth
L, Smith MC, Snijder MB, So HK, Sobngwi E, Söderberg S, Solfrizzi V, Sonestedt E,
Song Y, Sørensen TIA, Soric M, Jérome CS, Soumare A, Staessen JA, Starc G,
Stathopoulou MG, Stavreski B, Steene-Johannessen J, Stehle P, Stein AD, Stergiou

GS, Stessman J, Stieber J, Stöckl D, Stocks T, Stokwiszewski J, Stronks K,
Strufaldi MW, Sun CA, Sundström J, Sung YT, Suriyawongpaisal P, Sy RG, Shyong Tai
E, Tammesoo ML, Tamosiunas A, Tan EJ, Tang X, Tanser F, Tao Y, Tarawneh MR,
Tarqui-Mamani CB, Tautu OF, Taylor A, Theobald H, Theodoridis X, Thijs L, Thuesen
BH, Tjonneland A, Tolonen HK, Tolstrup JS, Topbas M, Topór-Madry R, Tormo MJ,
Torrent M, Traissac P, Trichopoulos D, Trichopoulou A, Trinh OTH, Trivedi A,
Tshepo L, Tulloch-Reid MK, Tullu F, Tuomainen TP, Tuomilehto J, Turley ML,
Tynelius P, Tzourio C, Ueda P, Ugel EE, Ulmer H, Uusitalo HMT, Valdivia G, Valvi
D, van der Schouw YT, Van Herck K, Van Minh H, van Rossem L, Van Schoor NM, van
Valkengoed IGM, Vanderschueren D, Vanuzzo D, Vatten L, Vega T, Velasquez-Melendez
G, Veronesi G, Monique Verschuren WM, Verstraeten R, Victora CG, Viet L,
Viikari-Juntura E, Vineis P, Vioque J, Virtanen JK, Visvikis-Siest S, Viswanathan
B, Vlasoff T, Vollenweider P, Voutilainen S, Wade AN, Wagner A, Walton J, Wan
Bebakar WM, Wan Mohamud WN, Wanderley RS Jr., Wang MD, Wang Q, Wang YX, Wang YW,
Wannamethee SG, Wareham N, Wedderkopp N, Weerasekera D, Whincup PH, Widhalm K,
Widyahening IS, Wiecek A, Wijga AH, Wilks RJ, Willeit J, Willeit P, Williams EA,
Wilsgaard T, Wojtyniak B, Wong-McClure RA, Wong JYY, Wong TY, Woo J, Woodward M,
Giwercman Wu A, Wu FC, Wu S, Xu H, Yan W, Yang X, Ye X, Yiallouros PK, Yoshihara
A, Younger-Coleman NO, Yusoff AF, Zainuddin AA, Zambon S, Zampelas A, Zdrojewski
T, Zeng Y, Zhao D, Zhao W, Zheng W, Zheng Y, Zhu D, Zhussupov B, Zimmermann E,
Cisneros JZ.
Background: Change in the prevalence of raised blood pressure could be due to
both shifts in the entire distribution of blood pressure (representing the
combined effects of public health interventions and secular trends) and changes
in its high-blood-pressure tail (representing successful clinical interventions
to control blood pressure in the hypertensive population). Our aim was to
quantify the contributions of these two phenomena to the worldwide trends in the
prevalence of raised blood pressure.
Methods: We pooled 1018 population-based studies with blood pressure measurements
on 88.6 million participants from 1985 to 2016. We first calculated mean systolic
blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of
raised blood pressure by sex and 10-year age group from 20-29 years to
70-79 years in each study, taking into account complex survey design and survey
sample weights, where relevant. We used a linear mixed effect model to quantify
the association between (probit-transformed) prevalence of raised blood pressure
and age-group- and sex-specific mean blood pressure. We calculated the
contributions of change in mean SBP and DBP, and of change in the prevalence-mean
association, to the change in prevalence of raised blood pressure.
Results: In 2005-16, at the same level of population mean SBP and DBP, men and
women in South Asia and in Central Asia, the Middle East and North Africa would
have the highest prevalence of raised blood pressure, and men and women in the
high-income Asia Pacific and high-income Western regions would have the lowest.
In most region-sex-age groups where the prevalence of raised blood pressure
declined, one half or more of the decline was due to the decline in mean blood
pressure. Where prevalence of raised blood pressure has increased, the change was
entirely driven by increasing mean blood pressure, offset partly by the change in
the prevalence-mean association.
Conclusions: Change in mean blood pressure is the main driver of the worldwide
change in the prevalence of raised blood pressure, but change in the
high-blood-pressure tail of the distribution has also contributed to the change
in prevalence, especially in older age groups.
DOI: 10.1093/ije/dyy016
PMCID: PMC6005056
PMID: 29579276
61. J Med Internet Res. 2018 Jun 8;20(6):e201. doi: 10.2196/jmir.9256.
Cost-Effectiveness of Facilitated Access to a Self-Management Website, Compared
to Usual Care, for Patients With Type 2 Diabetes (HeLP-Diabetes): Randomized

Controlled Trial.
Li J(1), Parrott S(1), Sweeting M(2), Farmer A(3), Ross J(4), Dack C(5), Pal
K(4), Yardley L(3)(6), Barnard M(7), Hudda M(8), Alkhaldi G(9), Murray E(4).
Author information:
(1)Mental Health and Addiction Research Group, Department of Health sciences,
University of York, York, United Kingdom.
(2)Cardiovascular Epidemiology Unit, Department of Public Health and Primary
Care, University of Cambridge, Cambridge, United Kingdom.
(3)Nuffield Department of Primary Care Health Sciences, University of Oxford,
Oxford, United Kingdom.
(4)Research Department of Primary Care and Population Health, University College
London, London, United Kingdom.
(5)Department of Psychology, University of Bath, Bath, United Kingdom.
(6)Department of Psychology, University of Southampton, Southampton, United
Kingdom.
(7)Department of Diabetes & Endocrinology, Whittington Health NHS Trust, London,
United Kingdom.
(8)Population Health Research Institute, St. George's University of London,
London, United Kingdom.
(9)Community Health Sciences Department, College of Applied Medical Sciences,
King Saud University, Riyadh, Saudi Arabia.
BACKGROUND: Type 2 diabetes mellitus is one of the most common long-term
conditions, and costs health services approximately 10% of their total budget.
Active self-management by patients improves outcomes and reduces health service
costs. While the existing evidence suggested that uptake of self-management
education was low, the development of internet-based technology might improve the
situation.
OBJECTIVE: To establish the cost-effectiveness of a Web-based self-management

program for people with type 2 diabetes (HeLP-Diabetes) compared to usual care.
METHODS: An incremental cost-effectiveness analysis was conducted, from a
National Health Service and personal and social services perspective, based on
data collected from a multi-center, two-arm individually randomized controlled
trial over 12 months. Adults aged 18 or over with a diagnosis of type 2 diabetes
and registered with the 21 participating general practices (primary care) in
England, UK, were approached. People who were unable to provide informed consent
or to use the intervention, terminally ill, or currently participating in a trial
of an alternative self-management intervention, were excluded. The participants
were then randomized to either usual care plus HeLP-Diabetes, an interactive,
theoretically-informed Web-based self-management program, or to usual care plus
access to a comparator website containing basic information only. The
participants' intervention costs and wider health care resource use were
collected as well as two health-related quality of life measures: the Problem
Areas in Diabetes (PAID) Scale and EQ-5D-3L. EQ-5D-3L was then used to calculate
quality-adjusted life years (QALYs). The primary analysis was based on
intention-to-treat, using multiple imputation to handle the missing data.
RESULTS: In total, 374 participants were randomized, with 185 in the intervention
group and 189 in the control group. The primary analysis showed incremental
cost-effectiveness ratios of £58 (95% CI -411 to 587) per unit improvement on
PAID scale and £5550 (95% CI -21,077 to 52,356) per QALY gained by HeLP-Diabetes,
compared to the control. The complete case analysis showed less
cost-effectiveness and higher uncertainty with incremental cost-effectiveness
ratios of £116 (95% CI -1299 to 1690) per unit improvement on PAID scale and
£18,500 (95% CI -203,949 to 190,267) per QALY. The cost-effectiveness
acceptability curve showed an 87% probability of cost-effectiveness at £20,000
per QALY willingness-to-pay threshold. The one-way sensitivity analyses estimated
363 users would be needed to use the intervention for it to become less costly
than usual care.
CONCLUSIONS: Facilitated access to HeLP-Diabetes is cost-effective, compared to
usual care, under the recommended threshold of £20,000 to £30,000 per QALY by
National Institute of Health and Care Excellence.
TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number
(ISRCTN) 02123133; http://www.controlled-trials.com/ISRCTN02123133 (Archived by
WebCite at http://www.webcitation.org/6zqjhmn00).
©Jinshuo Li, Steve Parrott, Michael Sweeting, Andrew Farmer, Jamie Ross,
Charlotte Dack, Kingshuk Pal, Lucy Yardley, Maria Barnard, Mohammed Hudda, Ghadah
Alkhaldi, Elizabeth Murray. Originally published in the Journal of Medical
Internet Research (http://www.jmir.org), 08.06.2018.
DOI: 10.2196/jmir.9256
PMCID: PMC6015272
PMID: 29884608
62. PLoS One. 2018 Oct 1;13(10):e0203992. doi: 10.1371/journal.pone.0203992.
eCollection 2018.
Cost of chronic kidney disease attributable to diabetes from the perspective of
the Brazilian Unified Health System.
Goncalves GMR(1), Silva END(1)(2).
Author information:
(1)University of Brasília, Brasília, Federal District, Brazil.
(2)National Institute os Science and Technology for health Technology Assessment
(IATS)-CNPq, Porto Alegre, Rio Grande do Sul, Brazil.
INTRODUCTION: Diabetes is the most common cause of chronic kidney disease, with a
high economic impact on health systems.
OBJECTIVE: To estimate the cost of chronic kidney disease (CKD) and end-stage
kidney disease (ESKD) attributable to diabetes, stratified by sex, race/skin
color, and age, from the perspective of the Brazilian public health system
between 2010 and 2016.
METHODS: Population attributable risk (PAR) was calculated from the Brazilian
prevalence of diabetes and the relative risk (or odds ratio) of persons with
diabetes developing CKD and ESKD as compared to non-diabetic subjects. The
variables of interest were sex, race/skin color, and age. A top-down approach was
used to measure the direct costs of the disease reimbursed by the Brazilian
Ministry of Health, using data from outpatient and inpatient records.
RESULTS: The cost of CKD and ESKD attributable to diabetes in the period
2010-2016 was US$1.2 billion (US$180 million per year) and trending upward.
Female sex, age 65-75, and black race/skin color contributed substantially to the
costs of CKD and ESKD (US$475 million, US$63 million, and US$25 million
respectively). The clinical procedures accounting for the greatest share of
disease-attributable costs are hemodialysis and peritoneal dialysis.
CONCLUSION: Diabetes accounted for 22% of the costs of CKD and ESKD. Female sex,
age 65-75 years, and black race/skin color were the variables which contributed
most to disease-related expenditure. The economic burden of CKD may increase
gradually in the coming years, with serious implications for the financial
sustainability of the Brazilian public health system.
PMCID: PMC6166929
PMID: 30273345
interests exist.
63. Br J Clin Pharmacol. 2018 Apr;84(4):679-693. doi: 10.1111/bcp.13490. Epub 2018
Jan 29.
Critical evaluation of causality assessment of herb-drug interactions in
patients.
Awortwe C(1)(2), Makiwane M(2), Reuter H(2), Muller C(1), Louw J(1), Rosenkranz
B(2).
Author information:
(1)Biomedical Research and Innovation Platform, South African Medical Research
Council, Tygerberg, 7505, South Africa.
(2)Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences,
University of Stellenbosch, Tygerberg, 7505, South Africa.
The aim of this review was to assess the severity of adverse drug reactions
(ADRs) due to herb-drug interactions (HDI) in patients taking herbs and
prescribed medications based on published evidence. Electronic databases of
PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or
nonrandomized clinical studies, case-control and case reports of HDI. The data
were extracted and the causal relationship of ADRs as consequences of HDI
assessed using Horn's drug interaction probability scale or Roussel Uclaf
Causality Assessment Method scoring systems. The mechanism of interaction was
ascertained using Stockley's herbal medicine interaction companion. Forty-nine
case reports and two observational studies with 15 cases of ADRs were recorded.
The majority of the patients were diagnosed with cardiovascular diseases
(30.60%), cancer (22.45%) and renal transplants (16.32%) receiving mostly
warfarin, alkylating agents and cyclosporine, respectively. HDI occurred in
patients resulting in clinical ADRs with different severity. Patients may poorly
respond to therapeutic agents or develop toxicity due to severe HDI, which in
either scenario may increase the cost of treatment and/or lead to or prolong
patient hospitalization. It is warranted to increase patient awareness of the
potential interaction between herbs and prescribed medicines and their

consequences to curb HDI as a potential health problem.
© 2018 The British Pharmacological Society.
DOI: 10.1111/bcp.13490
PMID: 29363155
64. J Epidemiol. 2018 Nov 5;28(11):465-469. doi: 10.2188/jea.JE20170093. Epub 2018
May 4.
Cumulative Risk of Type 2 Diabetes in a Working Population: The Japan
Epidemiology Collaboration on Occupational Health Study.
Hu H(1), Nakagawa T(2), Okazaki H(3), Nishiura C(4), Imai T(5), Miyamoto T(6),
Sasaki N(7), Yamamoto M(8), Murakami T(9), Kochi T(10), Eguchi M(10), Tomita
K(11), Nagahama S(12), Kuwahara K(1)(13), Kabe I(10), Mizoue T(1), Dohi S(3).
Author information:
(1)Department of Epidemiology and Prevention, National Center for Global Health
and Medicine.
(2)Hitachi, Ltd.
(3)Mitsui Chemicals, Inc.
(4)Tokyo Gas Co., Ltd.
(5)Azbil Corporation.
(6)Nippon Steel & Sumitomo Metal Corporation Kimitsu Works.
(7)Mitsubishi Fuso Truck and Bus Corporation.
(8)YAMAHA CORPORATION.
(9)Mizue Medical Clinic, Keihin Occupational Health Center.
(10)Furukawa Electric Co., Ltd.

(11)Mitsubishi Plastics, Inc.
(12)All Japan Labour Welfare Foundation.
(13)Teikyo University Graduate School of Public Health.
BACKGROUND: We estimated the cumulative risk of type 2 diabetes from age 30 to 65
years in a large working population in Japan.
METHODS: We used data from the Japan Epidemiology Collaboration on Occupational
Health Study. Participants (46,065 men and 7,763 women) were aged 30-59 years,
free of diabetes at baseline, and followed up for a maximum of 7 years. Incident
type 2 diabetes was defined based on fasting and casual glucose, glycated
hemoglobin, and current medical treatment for type 2 diabetes. We calculated the
sex-specific cumulative risk of type 2 diabetes using the Practical Incidence
Estimator macro, which was created to produce several estimates of disease
incidence for prospective cohort studies based on a modified Kaplan-Meier method.
RESULTS: During 274,349 person-years of follow-up, 3,587 individuals (3,339 men
and 248 women) developed type 2 diabetes. The cumulative risk was 34.7% (95%
confidence interval, 33.1-36.3%) for men and 18.6% (95% confidence interval,
15.5-21.7%) for women. In BMI-stratified analysis, obese (BMI ≥30 kg/m2) and
overweight (BMI 25-29.9 kg/m2) men and women had a much higher cumulative risk of
type 2 diabetes (obese: 77.3% for men and 64.8% for women; overweight: 49.1% and
35.7%, respectively) than those with BMI <25 kg/m2 (26.2% and 13.4% for men and
women, respectively).
CONCLUSIONS: The present data highlight the public health burden of type 2
diabetes in the working population. There is a need for effective programs for
weight management and type 2 diabetes screening, especially for young obese
employees, to prevent or delay the development of type 2 diabetes.
DOI: 10.2188/jea.JE20170093
PMCID: PMC6192974
PMID: 29731478
65. J Physiol Anthropol. 2018 Aug 29;37(1):20. doi: 10.1186/s40101-018-0181-y.
Current health status and its risk factors of the Tsarang villagers living at
high altitude in the Mustang district of Nepal.
Koirala S(1)(2)(3), Nakano M(4)(5), Arima H(1)(3), Takeuchi S(6), Ichikawa
T(1)(7), Nishimura T(8), Ito H(1)(9)(10), Pandey BD(11)(12), Pandey K(11)(13),
Wada T(1)(14), Yamamoto T(1)(2)(3).
Author information:
(1)Department of International Health, Institute of Tropical Medicine, Nagasaki
University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
(2)Leading Program, Graduate School of Biomedical Sciences, Nagasaki University,
1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
(3)Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto,
Nagasaki, 852-8523, Japan.
(4)Department of International Health, Institute of Tropical Medicine, Nagasaki
manakano@nagasaki-u.ac.jp.
(5)Department of Bacteriology, Institute of Tropical Medicine, Nagasaki
manakano@nagasaki-u.ac.jp.
(6)Department of Nutrition Science, Faculty of Nursing and Nutrition, University
of Nagasaki, 1-1-1 Manabino, Nagayo, Nishisonogi, Nagasaki, 851-2195, Japan.
(7)Department of Society and Regional Culture, Okinawa International University,
2-6-1 Ginowan, Ginowan City, Okinawa, 901-2701, Japan.
(8)Department of Public Health, Graduate School of Biomedical Sciences, Nagasaki
University, 1-12-4 Sakamoto, Nagasaki, Japan.
(9)Department of General System Studies, Graduate School of Arts and Sciences,
University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo, 153-8902, Japan.

(10)Department of Environmental Sciences, Zoology, University of Basel,
Vesalgasse 1, CH-4051, Basel, Switzerland.
(11)Everest International Clinic and Research Center, GPO 9045, Kathmandu, Nepal.
(12)National Center for AIDS & STD Control, Ministry of Health and Population,
GPO 9045, Teku, Kathmandu, Nepal.
(13)Nepal Academy of Science and Technology, GPO 3323, Khumaltar, Lalitpur,
Nepal.
(14)School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4
Sakamoto, Nagasaki, 852-8523, Japan.
BACKGROUND: Epidemiology of noncommunicable diseases (NCDs) such as obesity and
diabetes mellitus (DM) are influenced by multiple hosts and environmental
factors. This study aims to investigate the prevalence of NCDs and determine
their risk factors among the adults residing in an isolated village situated at a
rural highland of Nepal.
METHODS: A cross-sectional survey was conducted in a village located at 3570 m.
Each 188 randomly selected participants of age ≥ 18 years old answered a
questionnaire and took a full physical exam that included biomedical measurements
of glycosylated hemoglobin (HbA1c).
RESULTS: The prevalence of intermediate hyperglycemia and DM was 31.6% and 4.6%
respectively, and the prevalence of hypoxemia (SpO2 < 90%) was 27.1%. A multiple
logistic regression analysis for factors for the prevalence of glucose
intolerance (HbA1c ≥ 6%) revealed older age (odds ratio [OR] 1.11, 95% confidence
interval [CI] 1.06-1.16, for every 1 year increase) and SpO2 (OR for hypoxemia
3.58, 95% CI 1.20-10.68, vs SpO2 ≥ 90%).
CONCLUSIONS: Tibetan highlanders in the remote mountainous Mustang valley of
Nepal have high prevalence of impaired glucose metabolism which could be related
to hypoxemia imposed by the hypoxic conditions of high altitude living.
DOI: 10.1186/s40101-018-0181-y
PMCID: PMC6114060
66. Clin Nutr. 2018 Apr;37(2):712-718. doi: 10.1016/j.clnu.2017.02.022. Epub 2017 Mar
8.
Dairy intake and risk of type 2 diabetes.
Talaei M(1), Pan A(2), Yuan JM(3), Koh WP(4).
Author information:
Singapore. Electronic address: mohammad.talaei@u.nus.edu.
(2)Department of Epidemiology and Biostatistics, MOE Key Lab of Environment and
Health, School of Public Health, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, Hubei, China.
(3)Division of Cancer Control and Population Sciences, University of Pittsburgh
Cancer Institute, Pittsburgh, PA, USA; Department of Epidemiology, University of
Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Singapore; Duke-NUS Medical School Singapore, Singapore. Electronic address:
woonpuay.koh@duke-nus.edu.sg.
BACKGROUND & AIMS: The effect of total dairy products, milk, and calcium intake
on risk of type 2 diabetes (T2D) is uncertain, particularly in the Chinese
population.
METHODS: The present study was based on a prospective cohort of 63,257 Chinese
men and women aged 45-74 years during enrollment (1993-1998) in Singapore.
Dietary information was obtained using a validated 165-item semi-quantitative
food-frequency questionnaire. Information about newly diagnosed T2D was collected
by self-report during two follow-up interviews in 1999-2004 and 2006-2010. Cox

proportional hazard regression method was used to estimate hazard ratios (HRs)
and their 95% confidence intervals (CIs) in 45,411 eligible participants.
RESULTS: Incidence rate (95% CI) of T2D was 10.5 (10.2-10.8) per 1000
person-years. Intake of dairy food was significantly associated with reduced T2D
risk; compared with the lowest quartile, HRs (95% CI) for the second, third and
fourth quartiles of dairy intake were 0.98 (0.91-1.06), 0.96 (0.89-1.03) and 0.90
(0.83-0.98), respectively, after adjustment for potential confounders at baseline
(P-trend = 0.01). Daily drinkers of milk had a significant 12% reduction in T2D
risk compared with non-drinkers. While dairy calcium was associated with a
decreased risk of T2D (HR comparing extreme quartiles 0.84; 95% CI 0.76-0.93;
P-trend = 0.001), no association was found for non-dairy calcium (HR 1.02; 95% CI
0.92-1.14; P-trend = 0.61).
CONCLUSIONS: In this large cohort study of Chinese adults, dairy product intake
and daily milk consumption was associated with a statistically significant,
although modest, decrease in risk of developing T2D, which may be independent of
its calcium content.
Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and
Metabolism. All rights reserved.
DOI: 10.1016/j.clnu.2017.02.022
PMID: 28318689
67. PLoS One. 2017 Jan 25;12(1):e0170219. doi: 10.1371/journal.pone.0170219.
eCollection 2017.
Deaths Attributable to Diabetes in the United States: Comparison of Data Sources
and Estimation Approaches.

Stokes A(1), Preston SH(2).
Author information:
(1)Department of Global Health and Center for Global Health and Development,
Boston University School of Public Health, Boston, Massachusetts, United States
of America.
(2)Department of Sociology and Population Studies Center, University of
Pennsylvania, Philadelphia, Pennsylvania, United States of America.
OBJECTIVE: The goal of this research was to identify the fraction of deaths
attributable to diabetes in the United States.
RESEARCH DESIGN AND METHODS: We estimated population attributable fractions (PAF)
for cohorts aged 30-84 who were surveyed in the National Health Interview Survey
(NHIS) between 1997 and 2009 (N = 282,322) and in the National Health and
Nutrition Examination Survey (NHANES) between 1999 and 2010 (N = 21,814). Cohort
members were followed prospectively for mortality through 2011. We identified
diabetes status using self-reported diagnoses in both NHIS and NHANES and using
HbA1c in NHANES. Hazard ratios associated with diabetes were estimated using Cox
model adjusted for age, sex, race/ethnicity, educational attainment, and smoking
status.
RESULTS: We found a high degree of consistency between data sets and definitions
of diabetes in the hazard ratios, estimates of diabetes prevalence, and estimates
of the proportion of deaths attributable to diabetes. The proportion of deaths
attributable to diabetes was estimated to be 11.5% using self-reports in NHIS,
11.7% using self-reports in NHANES, and 11.8% using HbA1c in NHANES. Among the
sub-groups that we examined, the PAF was highest among obese persons at 19.4%.
The proportion of deaths in which diabetes was assigned as the underlying cause
of death (3.3-3.7%) severely understated the contribution of diabetes to
mortality in the United States.
CONCLUSION: Diabetes may represent a more prominent factor in American mortality
than is commonly appreciated, reinforcing the need for robust population-level

interventions aimed at diabetes prevention and care.
PMCID: PMC5266275
interests exist.
68. BMJ Open Diabetes Res Care. 2018 May 29;6(1):e000521. doi:
Declining trends of diabetic nephropathy, retinopathy and neuropathy with
improving diabetes care indicators in Japanese patients with type 2 and type 1
diabetes (JDDM 46).
Yokoyama H(1), Araki SI(2), Kawai K(3), Yamazaki K(3), Tomonaga O(4), Shirabe
SI(5), Maegawa H(2).
Author information:
(1)Internal Medicine, Jiyugaoka Medical Clinic, Obihiro, Japan.
(2)Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
(3)Kawai Clinic, Tsukuba, Japan.
(4)Tomonaga Clinic, Tokyo, Japan.
(5)HEC Science Clinic, Yokohama, Japan.
Objective: We examined changes in prevalence of diabetic
microvascular/macrovascular complications and diabetes care indicators for adults
in Japan with type 2 and type 1 diabetes over one decade.
Research design and methods: Two independent cohorts were recruited with the same
inclusion criteria in 2004 (cohort 1: 3319 with type 2 and 286 with type 1
diabetes) and in 2014 (cohort 2: 3932 with type 2 and 308 with type 1 diabetes).
Prevalence of complications and care indicators including achieving treatment
targets for glycemia, blood pressure, lipid control, body mass index (BMI), and
smoking were compared. In addition, patients in cohort 1 were re-examined in 2014
and their data were compared with the baseline data of each cohort.
Results: In type 2 diabetes, the prevalence of nephropathy, retinopathy,
neuropathy, chronic kidney disease, current smoking and stroke significantly
decreased, with improvements in achieving treatment target rates in cohort 2 two
as compared with cohort 1. In type 1 diabetes, the prevalence of nephropathy,
retinopathy, chronic kidney disease, and hemoglobin A1Cvalues significantly
decreased. Decreases in prevalence of microvascular complications in type 2
diabetes were similarly found in each age-matched and sex-matched group, whereas
younger patients exhibited marked increase in BMI and lower treatment target
achieving rates compared with elderly patients. Regarding normoalbuminuric renal
impairment, only a slight increase in the prevalence was observed both in type 2
and type 1 diabetes. In cohort 1, re-examined in 2014, care indicators were
significantly improved from 2004, while complications increased with getting 10
years older.
Conclusions: We observed declining trends of diabetic microvascular complications
with improvement in diabetes care indicators in type 2 and type 1 diabetes.
Younger patients with type 2 diabetes exhibited marked increase in BMI and lower
rates of achieving treatment targets compared with elderly patients, which
remains a concern.
DOI: 10.1136/bmjdrc-2018-000521
PMCID: PMC5992467
PMID: 29892340

69. Diabetologia. 2018 Nov;61(11):2310-2318. doi: 10.1007/s00125-018-4681-4. Epub
2018 Jul 11.
Decreasing incidence of pharmacologically and non-pharmacologically treated type
2 diabetes in Norway: a nationwide study.
Ruiz PLD(1)(2)(3), Stene LC(4), Bakken IJ(5), Håberg SE(5), Birkeland KI(6)(7),
Gulseth HL(4)(8).
Author information:
(1)Department of Chronic Diseases and Ageing, Norwegian Institute of Public
Health, Post box 4404, Nydalen, 0403, Oslo, Norway. Paz.Lopez-Doriga.Ruiz@fhi.no.
University Hospital, Oslo, Norway. Paz.Lopez-Doriga.Ruiz@fhi.no.
(3)Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Paz.Lopez-Doriga.Ruiz@fhi.no.
(4)Department of Chronic Diseases and Ageing, Norwegian Institute of Public
Health, Post box 4404, Nydalen, 0403, Oslo, Norway.
(5)Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo,
Norway.
(6)Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
(7)Department of Transplantation Medicine, Oslo University Hospital, Oslo,
Norway.
University Hospital, Oslo, Norway.
AIMS/HYPOTHESIS: This study aimed to examine recent time trends in the incidence
and prevalence of type 2 diabetes in Norway.
METHODS: In this Norwegian nationwide cohort study, we linked data from national
registries with prospectively collected data on diabetes medication and diabetes

diagnoses for all residents in Norway aged 30 to 89 years (>3.2 million people).
We analysed trends in incidence and prevalence of type 2 diabetes from 2009 to
2014 by type of treatment, sex, age, education level and place of birth.
RESULTS: During 15,463,691 person-years of follow-up from 2009 to 2014, we
identified 75,496 individuals with new-onset type 2 diabetes. Of these, 36,334
(48%) were treated with blood-glucose-lowering drugs within 6 months of
diagnosis. A low education level and being born in Asia, Africa or South America
were significant risk factors for incident type 2 diabetes. While the prevalence
of type 2 diabetes increased from 4.9% to 6.1% during the study period, the
incidence decreased significantly from 609 cases per 100,000 person-years in 2009
to 398 cases per 100,000 in 2014, an annual reduction of 10.1% (95% CI -10.5,
-9.6). A declining incidence was seen for both pharmacologically and
non-pharmacologically treated type 2 diabetes, and in all subgroups defined by
sex, age group, education level and place of birth.
CONCLUSIONS/INTERPRETATIONS: This nationwide study shows that, despite a
decreasing incidence of type 2 diabetes in Norway, the prevalence continues to
rise, probably due to diagnosis at a younger age and increased longevity.
DOI: 10.1007/s00125-018-4681-4
PMCID: PMC6182655
PMID: 29995214
70. Asian Pac J Cancer Prev. 2017 Sep 27;18(9):2485-2491.
Demographic Characteristics, Survival and Prognostic Factors of Early Breast
Cancer Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cohort Study
Behrouzi B(1), Mohagheghi MA, Sadighi S.
Author information:
(1)Department of Physiology, University of Toronto, St George Campus, Toronto,
Canada. Email: ssadighi@tums.ac.ir
Objective: With increasing prevalence of type 2 diabetes mellitus and breast
cancer in Iran, we aimed to search hospital registries of breast cancer patients
to investigate type 2 diabetes mellitus association with survival outcomes of
early breast cancer after adjustment of confounding factors. Methods: In a
retrospective cohort study conducted from July 2003 to Feb 2014 and followed up
until death or December 2016, female patients with early breast cancer who have
been treated for the first time at the Cancer Institute of Iran, were divided to
diabetic and non-diabetic groups. Primary and secondary outcomes were relapse
free survival (RFS) and overall survival (OS). SPSS version 23 was used for
analysis of data. Other variables included age, tumor stage, hormone receptor
status, tumor subtype, and patient’s body mass index (BMI). Result: From a total
of 1021 patients, 218 (21.4%) had type 2 diabetes mellitus. Diabetic patients had
a higher mean age (53.31 vs 47.00), higher mean BMI (31.13 vs 29.15), lower HER2
expression (20.8% vs 32.1%) and higher frequency of luminal A subtype (61.1% vs
51.0). Overall, after adjustment of other variables, diabetes status did not
affect RFS or OS independently. However, in luminal A subgroup, patients with
diabetes mellitus had significantly lower survival outcomes of OS (135.277 vs
154.701) and RFS (114.107 vs 133.612) as well as OS higher hazard ratio of 1.830
and RFS hazard ratio of 1.663 compared to non-diabetic patients. BMI, hormone
receptor status and tumor stage significantly affected the survival of the
patients. Conclusion: In the present study, in addition to known breast cancer
risk factors, BMI and type 2 diabetes mellitus had an independent impact on
survival of the patients, highlighting the importance of health issues such as
obesity and diabetes suboptimal performance in the treatment outcomes of early
breast cancer patients in Iran.
Creative Commons Attribution License

DOI: 10.22034/APJCP.2017.18.9.2485
PMCID: PMC5720655
PMID: 28952281
71. Graefes Arch Clin Exp Ophthalmol. 2018 Jan;256(1):49-58. doi:
10.1007/s00417-017-3828-1. Epub 2017 Oct 28.
Detailed analysis of retinal morphology in patients with diabetic macular edema
(DME) randomized to ranibizumab or triamcinolone treatment.
Karst SG(1), Lammer J(1), Mitsch C(1), Schober M(1), Mehta J(1)(2), Scholda C(1),
Kundi M(3), Kriechbaum K(1), Schmidt-Erfurth U(4).
Author information:
(1)Department of Ophthalmology and Optometry, Medical University Vienna, Vienna,
Austria.
(2)Jaslok Hospital and Research Centre, Mumbai, India.
(3)Center of Public Health, Medical University Vienna, Vienna, Austria.
(4)Department of Ophthalmology and Optometry, Medical University Vienna, Vienna,
Austria. ursula.schmidt-erfurth@meduniwien.ac.at.
Comment in
Graefes Arch Clin Exp Ophthalmol. 2018 May;256(5):1039-1040.
Graefes Arch Clin Exp Ophthalmol. 2018 May;256(5):1035-1037.
PURPOSE: Our purpose was to compare the impact in diabetic macula edema (DME) of
two intravitreal drugs (0.5 mg ranibizumab vs. 8 mg triamcinolone) on changes in
retinal morphology in spectral-domain optical coherence tomography (SD OCT)
images, color fundus photography (CF) and fluorescein angiography (FA) images
during a 1-year follow-up.

METHODS: Post hoc analysis was conducted of morphologic characteristics in OCT,
FA and CF images of eyes with a center involving DME that were included in a
prospective double-masked randomized trial. Eligible patients were divided at
random into two groups receiving either pro re nata treatment with 0.5 mg
ranibizumab or 8 mg triamcinolone after a fixed loading dose. OCT and CF images
were acquired at monthly visits and FA images every three months.
RESULTS: Twenty-five eyes of 25 patients (ranibizumab: n = 10; triamcinolone:
n = 15) were included in this study. Patients treated with ranibizumab showed
better visual acuity results after 12 months than patients receiving
triamcinolone (p = 0.015) although edema reduction was similar (p = 0.426) in
both groups. The initial effect on macular edema shedding after a single
ranibizumab injection could be amplified with the following two injections of the
loading dose. After a single injection of triamcinolone the beneficial initial
effect on the macula edema faded within 3 months. Subretinal fluid and INL
cystoid spaces diminished early in the course of treatment while fluid
accumulation in the ONL seemed to be more persistent in both treatment arms. In
FA, the area of leakage diminished significantly in both treatment arms. After
repeated injections the morphologic OCT and FA characteristics of the treatment
arms converged.
CONCLUSIONS: Despite the higher dosage of triamcinolone, both therapies were safe
and effective for treating diabetic macular edema. Fluid accumulation in the INL
and subretinal space was more responsive to therapy than fluid accumulation in
the ONL. Clinicaltrials.gov : NCT00682539.
DOI: 10.1007/s00417-017-3828-1
PMCID: PMC5748439
72. Cancer Epidemiol. 2016 Dec;45 Suppl 1:S4-S12. doi: 10.1016/j.canep.2016.10.003.
Epub 2016 Oct 7.

Developing and testing a cost data collection instrument for noncommunicable
disease registry planning.
Subramanian S(1), Tangka F(2), Edwards P(3), Hoover S(3), Cole-Beebe M(3).
Author information:
(1)RTI International, 3040 E. Cornwallis Rd., Research Triangle Park, NC, USA.
Electronic address: ssubramanian@rti.org.
(2)Centers for Disease Control and Prevention, 4770 Buford Hwy, Atlanta, GA, USA.
(3)RTI International, 3040 E. Cornwallis Rd., Research Triangle Park, NC, USA.
BACKGROUND: This article reports on the methods and framework we have developed
to guide economic evaluation of noncommunicable disease registries.
METHODS: We developed a cost data collection instrument, the Centers for Disease
Control and Prevention's (CDC's) International Registry Costing Tool
(IntRegCosting Tool), based on established economics methods We performed
in-depth case studies, site visit interviews, and pilot testing in 11 registries
from multiple countries including India, Kenya, Uganda, Colombia, and Barbados to
assess the overall quality of the data collected from cancer and cardiovascular
registries.
RESULTS: Overall, the registries were able to use the IntRegCosting Tool to
assign operating expenditures to specific activities. We verified that registries
were able to provide accurate estimation of labor costs, which is the largest
expenditure incurred by registries. We also identified several factors that can
influence the cost of registry operations, including size of the geographic area
served, data collection approach, local cost of living, presence of rural areas,
volume of cases, extent of consolidation of records to cases, and continuity of
funding.
CONCLUSION: Internal and external registry factors reveal that a single estimate
for the cost of registry operations is not feasible; costs will vary on the basis
of factors that may be beyond the control of the registries. Some factors, such
as data collection approach, can be modified to improve the efficiency of
registry operations. These findings will inform both future economic data
collection using a web-based tool and cost and cost-effectiveness analyses of
registry operations in low- and middle-income countries (LMICs) and other
locations with similar characteristics.
DOI: 10.1016/j.canep.2016.10.003
PMCID: PMC5840872
73. J Diabetes Res. 2016;2016:8790235. Epub 2016 Sep 4.
Development and Validation of a Simple Risk Score for Undiagnosed Type 2 Diabetes
in a Resource-Constrained Setting.
Bernabe-Ortiz A(1), Smeeth L(2), Gilman RH(3), Sanchez-Abanto JR(4), Checkley
W(5), Miranda JJ(6), Study Group CC(7).
Author information:
Cayetano Heredia, Lima, Peru; Faculty of Epidemiology and Population Health,
London School of Hygiene and Tropical Medicine, London, UK.
Tropical Medicine, London, UK.
Cayetano Heredia, Lima, Peru; Department of International Health, Bloomberg
School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Área de
Investigación y Desarrollo, Asociación Benéfica PRISMA, Lima, Peru.
(4)Centro Nacional de Alimentación y Nutrición, Instituto Nacional de Salud,
Lima, Peru.
Cayetano Heredia, Lima, Peru; Division of Pulmonary and Critical Care, School of
Medicine, Johns Hopkins University, Baltimore, MD, USA.
Cayetano Heredia, Lima, Peru; Department of Medicine, School of Medicine,
Universidad Peruana Cayetano Heredia, Lima, Peru.
(7)Universidad Peruana Cayetano Heredia, Lima, Peru.
Objective. To develop and validate a risk score for detecting cases of
undiagnosed diabetes in a resource-constrained country. Methods. Two
population-based studies in Peruvian population aged ≥35 years were used in the
analysis: the ENINBSC survey (n = 2,472) and the CRONICAS Cohort Study (n =
2,945). Fasting plasma glucose ≥7.0 mmol/L was used to diagnose diabetes in both
studies. Coefficients for risk score were derived from the ENINBSC data and then
the performance was validated using both baseline and follow-up data of the
CRONICAS Cohort Study. Results. The prevalence of undiagnosed diabetes was 2.0%
in the ENINBSC survey and 2.9% in the CRONICAS Cohort Study. Predictors of
undiagnosed diabetes were age, diabetes in first-degree relatives, and waist
circumference. Score values ranged from 0 to 4, with an optimal cutoff ≥2 and had
a moderate performance when applied in the CRONICAS baseline data (AUC = 0.68;
95% CI: 0.62-0.73; sensitivity 70%; specificity 59%). When predicting incident
cases, the AUC was 0.66 (95% CI: 0.61-0.71), with a sensitivity of 69% and
specificity of 59%. Conclusions. A simple nonblood based risk score based on age,
diabetes in first-degree relatives, and waist circumference can be used as a
simple screening tool for undiagnosed and incident cases of diabetes in Peru.
DOI: 10.1155/2016/8790235
PMCID: PMC5027039
PMID: 27689096
74. Diabetologia. 2018 Oct;61(10):2079-2086. doi: 10.1007/s00125-018-4654-7. Epub
2018 Aug 22.
Development of SGLT1 and SGLT2 inhibitors.
Rieg T(1), Vallon V(2)(3)(4).
Author information:
(1)Department of Molecular Pharmacology and Physiology, University of South
Florida, 12901 Bruce B. Downs Blvd, Tampa, FL, 33592, USA. trieg@health.usf.edu.
(2)Department of Medicine, Division of Nephrology and Hypertension, University of
California San Diego, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.
vvallon@ucsd.edu.
(3)Department of Pharmacology, University of California San Diego, La Jolla, CA,
USA. vvallon@ucsd.edu.
(4)VA San Diego Healthcare System, San Diego California, San Diego, CA, USA.
vvallon@ucsd.edu.
Sodium-glucose cotransporters SGLT1 (encoded by SGLT1, also known as SLC5A1) and
SGLT2 (encoded by SGLT2, also known as SLC5A2) are important mediators of
epithelial glucose transport. While SGLT1 accounts for most of the dietary
glucose uptake in the intestine, SGLT2 is responsible for the majority of glucose
reuptake in the tubular system of the kidney, with SGLT1 reabsorbing the
remainder of the filtered glucose. As a consequence, mutations in the SLC5A1 gene
cause glucose/galactose malabsorption, whereas mutations in SLC5A2 are associated
with glucosuria. Since the cloning of SGLT1 more than 30 years ago, big strides
have been made in our understanding of these transporters and their suitability
as drug targets. Phlorizin, a naturally occurring competitive inhibitor of SGLT1

and SGLT2, provided the first insights into potential efficacy, but its use was
hampered by intestinal side effects and a short half-life. Nevertheless, it was a
starting point for the development of specific inhibitors of SGLT1 and SGLT2, as
well as dual SGLT1/2 inhibitors. Since the approval of the first SGLT2 inhibitor
in 2013 by the US Food and Drug Administration, SGLT2 inhibitors have become a
new mainstay in the treatment of type 2 diabetes mellitus. They also have
beneficial effects on the cardiovascular system (including heart failure) and the
kidney. This review focuses on the rationale for the development of individual
SGLT2 and SGLT1 inhibitors, as well as dual SGLT1/2 inhibition, including, but
not limited to, aspects of genetics, genetically modified mouse models,
mathematical modelling and general considerations of drug discovery in the field
of metabolism.
DOI: 10.1007/s00125-018-4654-7
PMID: 30132033
75. Diabetes Ther. 2018 Jun;9(3):1217-1232. doi: 10.1007/s13300-018-0430-4. Epub 2018
Apr 30.
DEVOTE 5: Evaluating the Short-Term Cost-Utility of Insulin Degludec Versus
Insulin Glargine U100 in Basal-Bolus Regimens for Type 2 Diabetes in the UK.
Pollock RF(1), Valentine WJ(2), Marso SP(3), Gundgaard J(4), Hallén N(4), Hansen
LL(4), Tutkunkardas D(4), Buse JB(5); DEVOTE Study Group.
Author information:
(1)Ossian Health Economics and Communications GmbH, Basel, Switzerland.
pollock@ossianconsulting.com.
(2)Ossian Health Economics and Communications GmbH, Basel, Switzerland.

(3)HCA Midwest Health Heart and Vascular Institute, Kansas City, MO, USA.
(4)Novo Nordisk A/S, Søborg, Denmark.
(5)University of North Carolina School of Medicine, Medicine/Endocrinology,
Chapel Hill, NC, USA.
INTRODUCTION: The aim of this study was to evaluate the short-term cost-utility
of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine
U100) for the treatment of type 2 diabetes in the basal-bolus subgroup of the
head-to-head cardiovascular (CV) outcome trial, DEVOTE.
METHODS: A cost-utility analysis was conducted over a 2-year time horizon using a
decision analytic model to compare costs in patients receiving once daily
degludec or glargine U100, both as part of a basal-bolus regimen, in addition to
standard care. Clinical outcomes and patient characteristics were taken
exclusively from DEVOTE, whilst health-related quality of life utilities and
UK-specific costs (expressed in 2016 GBP) were obtained from the literature. The
analysis was conducted from the perspective of the National Health Service.
RESULTS: Degludec was associated with mean cost savings of GBP 28.78 per patient
relative to glargine U100 in patients with type 2 diabetes at high CV risk. Cost
savings were driven by the reduction in risk of diabetes-related complications
with degludec, which offset the higher treatment costs relative to glargine U100.
Degludec was associated with a mean improvement of 0.0064 quality-adjusted
life-years (QALYs) compared with glargine U100, with improvements driven
predominantly by lower rates of severe hypoglycemia with degludec versus glargine
U100. Improvements in quality-adjusted life expectancy combined with cost
neutrality resulted in degludec being dominant over glargine U100. Sensitivity
analyses demonstrated that the incremental cost-utility ratio was stable to
variations in the majority of model inputs.
CONCLUSION: The present short-term modeling analysis found that for the
basal-bolus subgroup of patients in DEVOTE, with a high risk of CV events,
degludec was cost neutral (no additional costs) compared with glargine U100 over
a 2-year time horizon in the UK setting. Furthermore, there were QALY gains with
degludec, particularly due to the reduction in the risk of severe hypoglycemia.
FUNDING: Novo Nordisk A/S.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01959529.
DOI: 10.1007/s13300-018-0430-4
PMCID: PMC5984933
PMID: 29713962
76. Clin Nutr Res. 2018 Oct;7(4):229-240. doi: 10.7762/cnr.2018.7.4.229. Epub 2018
Oct 23.
Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects.
Lee HJ(1), Seo HI(1), Cha HY(1), Yang YJ(1), Kwon SH(1), Yang SJ(1).
Author information:
(1)Department of Food and Nutrition, Seoul Women's University, Seoul 01797,
Korea.
Blood glucose homeostasis is well maintained by coordinated control of various
hormones including insulin and glucagon as well as cytokines under normal
conditions. However, chronic exposure to diabetic environment with high fat/high
sugar diets and physical/mental stress can cause hyperglycemia, one of main
characteristics of insulin resistance, metabolic syndrome, and diabetes.
Hyperglycemia impairs organogenesis and induces organ abnormalities such as
cardiac defect in utero. It is a risk factor for the development of metabolic
diseases in adults. Resulting glucotoxicity affects peripheral tissues and
vessels, causing pathological complications including diabetic neuropathy,
nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic
exposure to hyperglycemia can deteriorate cognitive function and other aspects of

mental health. Recent reports have demonstrated that hyperglycemia is closely
related to the development of cognitive impairment and dementia, suggesting that
there may be a cause-effect relationship between hyperglycemia and dementia. With
increasing interests in aging-related diseases and mental health,
diabetes-related cognitive impairment is attracting great attention. It has been
speculated that glucotoxicity can result in structural damage and functional
impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and
increased accumulation of amyloid beta. These are potential mechanisms underlying
diabetes-related dementia. Nutrients and natural food components have been
investigated as preventive and/or intervention strategy. Among candidate
components, resveratrol, curcumin, and their analogues might be beneficial for
the prevention of diabetes-related cognitive impairment. The purposes of this
review are to discuss recent experimental evidence regarding diabetes and
cognitive impairment and to suggest potential nutritional intervention strategies
for the prevention and/or treatment of diabetes-related dementia.
DOI: 10.7762/cnr.2018.7.4.229
PMCID: PMC6209735
PMID: 30406052
Conflict of interest statement: Conflict of Interest: The authors declare that
they have no competing interests.
77. JAMA Intern Med. 2018 Mar 1;178(3):363-372. doi: 10.1001/jamainternmed.2017.8094.
Diabetes and Hypertension in India: A Nationally Representative Study of 1.3
Million Adults.
Geldsetzer P(1), Manne-Goehler J(1)(2), Theilmann M(3), Davies JI(4)(5), Awasthi
A(6), Vollmer S(1)(3), Jaacks LM(1)(7), Bärnighausen T(1)(8)(9), Atun R(1).

Author information:
(1)Department of Global Health and Population, Harvard T. H. Chan School of
Public Health, Boston, Massachusetts.
(2)Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, Massachusetts.
(3)Department of Economics & Centre for Modern Indian Studies, University of
Goettingen, Göttingen, Germany.
(4)MRC/Wits Rural Public Health and Health Transitions Research Unit, School of
Public Health, Education Campus, University of Witwatersrand, Johannesburg, South
Africa.
(5)Centre for Global Health, King's College London, London, England.
(6)Indian Institute of Public Health, Gandhinagar, India.
(7)Public Health Foundation of India, Delhi NCR, India.
(8)Institute of Public Health, Heidelberg University, Heidelberg, Germany.
(9)Africa Health Research Institute, Mtubatuba, South Africa.
Importance: Understanding how diabetes and hypertension prevalence varies within
a country as large as India is essential for targeting of prevention, screening,
and treatment services. However, to our knowledge there has been no prior
nationally representative study of these conditions to guide the design of
effective policies.
Objective: To determine the prevalence of diabetes and hypertension in India, and
its variation by state, rural vs urban location, and individual-level
sociodemographic characteristics.
Design, Setting, and Participants: This was a cross-sectional, nationally
representative, population-based study carried out between 2012 and 2014. A total
of 1 320 555 adults 18 years or older with plasma glucose (PG) and blood pressure
(BP) measurements were included in the analysis.
Exposures: State, rural vs urban location, age, sex, household wealth quintile,
education, and marital status.

Main Outcomes and Measures: Diabetes (PG level ≥126 mg/dL if the participant had
fasted or ≥200 mg/dL if the participant had not fasted) and hypertension
(systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg).
Results: Of the 1 320 555 adults, 701 408 (53.1%) were women. The crude
prevalence of diabetes and hypertension was 7.5% (95% CI, 7.3%-7.7%) and 25.3%
(95% CI, 25.0%-25.6%), respectively. Notably, hypertension was common even among
younger age groups (eg, 18-25 years: 12.1%; 95% CI, 11.8%-12.5%). Being in the
richest household wealth quintile compared with being in the poorest quintile was
associated with only a modestly higher probability of diabetes (rural: 2.81
percentage points; 95% CI, 2.53-3.08 and urban: 3.47 percentage points; 95% CI,
3.03-3.91) and hypertension (rural: 4.15 percentage points; 95% CI, 3.68-4.61 and
urban: 3.01 percentage points; 95% CI, 2.38-3.65). The differences in the
probability of both conditions by educational category were generally small (≤2
percentage points). Among states, the crude prevalence of diabetes and
hypertension varied from 3.2% (95% CI, 2.7%-3.7%) to 19.9% (95% CI, 17.6%-22.3%),
and 18.0% (95% CI, 16.6%-19.5%) to 41.6% (95% CI, 37.8%-45.5%), respectively.
Conclusions and Relevance: Diabetes and hypertension prevalence is high in middle
and old age across all geographical areas and sociodemographic groups in India,
and hypertension prevalence among young adults is higher than previously thought.
Evidence on the variations in prevalence by state, age group, and rural vs urban
location is critical to effectively target diabetes and hypertension prevention,
screening, and treatment programs to those most in need.
DOI: 10.1001/jamainternmed.2017.8094
PMID: 29379964
78. Front Endocrinol (Lausanne). 2017 Oct 30;8:271. doi: 10.3389/fendo.2017.00271.
eCollection 2017.
Diabetes and Sepsis: Risk, Recurrence, and Ruination.
Frydrych LM(1), Fattahi F(2), He K(1), Ward PA(2), Delano MJ(1).
Author information:
(1)Department of Surgery, Division of Acute Care Surgery, University of Michigan,
Ann Arbor, MI, United States.
(2)Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Sepsis develops when an infection surpasses local tissue containment. A series of
dysregulated physiological responses are generated, leading to organ dysfunction
and a 10% mortality risk. When patients with sepsis demonstrate elevated serum
lactates and require vasopressor therapy to maintain adequate blood pressure in
the absence of hypovolemia, they are in septic shock with an in-hospital
mortality rate >40%. With improvements in intensive care treatment strategies,
overall sepsis mortality has diminished to ~20% at 30 days; however, mortality
continues to steadily climb after recovery from the acute event. Traditionally,
it was thought that the complex interplay between inflammatory and
anti-inflammatory responses led to sepsis-induced organ dysfunction and
mortality. However, a closer examination of those who die long after sepsis
subsides reveals that many initial survivors succumb to recurrent, nosocomial,
and secondary infections. The comorbidly challenged, physiologically frail
diabetic individuals suffer the highest infection rates. Recent reports suggest
that even after clinical "recovery" from sepsis, persistent alterations in innate
and adaptive immune responses exists resulting in chronic inflammation, immune
suppression, and bacterial persistence. As sepsis-associated immune defects are
associated with increased mortality long-term, a potential exists for immune
modulatory therapy to improve patient outcomes. We propose that diabetes causes a
functional immune deficiency that directly reduces immune cell function. As a
result, patients display diminished bactericidal clearance, increased infectious
complications, and protracted sepsis mortality. Considering the substantial

expansion of the elderly and obese population, global adoption of a Western diet
and lifestyle, and multidrug resistant bacterial emergence and persistence,
diabetic mortality from sepsis is predicted to rise dramatically over the next
two decades. A better understanding of the underlying diabetic-induced immune
cell defects that persist following sepsis are crucial to identify potential
therapeutic targets to bolster innate and adaptive immune function, prevent
infectious complications, and provide more durable diabetic survival.
DOI: 10.3389/fendo.2017.00271
PMCID: PMC5670360
PMID: 29163354
79. Diabetes Care. 2018 Aug;41(8):1646-1653. doi: 10.2337/dc18-0277. Epub 2018 Jun 1.
Diabetes and Trajectories of Estimated Glomerular Filtration Rate: A Prospective
Cohort Analysis of the Atherosclerosis Risk in Communities Study.
Warren B(1), Rebholz CM(1), Sang Y(1), Lee AK(1), Coresh J(1)(2), Selvin E(1)(2),
Grams ME(3)(2).
Author information:
(1)Department of Epidemiology and the Welch Center for Prevention, Epidemiology
and Clinical Research, Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD.
(2)Johns Hopkins University School of Medicine, Baltimore, MD.
(3)Department of Epidemiology and the Welch Center for Prevention, Epidemiology
and Clinical Research, Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD mgrams2@jhmi.edu.
OBJECTIVE: To characterize long-term kidney disease trajectories in persons with

and without diabetes in a general population.
RESEARCH DESIGN AND METHODS: We classified 15,517 participants in the
community-based Atherosclerosis Risk in Communities (ARIC) study by diabetes
status at baseline (1987-1989; no diabetes, undiagnosed diabetes, and diagnosed
diabetes). We used linear mixed models with random intercepts and slopes to
quantify estimated glomerular filtration rate (eGFR) trajectories at four visits
over 26 years.
RESULTS: Adjusted mean eGFR decline over the full study period among participants
without diabetes was -1.4 mL/min/1.73 m2/year (95% CI -1.5 to -1.4), with
undiagnosed diabetes was -1.8 mL/min/1.73 m2/year (95% CI -2.0 to -1.7)
(difference vs. no diabetes, P < 0.001), and with diagnosed diabetes was -2.5
mL/min/1.73 m2/year (95% CI -2.6 to -2.4) (difference vs. no diabetes, P <
0.001). Among participants with diagnosed diabetes, risk factors for steeper eGFR
decline included African American race, APOL1 high-risk genotype, systolic blood
pressure ≥140 mmHg, insulin use, and higher HbA1c.
CONCLUSIONS: Diabetes is an important risk factor for kidney function decline.
Those with diagnosed diabetes declined almost twice as rapidly as those without
diabetes. Among people with diagnosed diabetes, steeper declines were seen in
those with modifiable risk factors, including hypertension and glycemic control,
suggesting areas for continued targeting in kidney disease prevention.
DOI: 10.2337/dc18-0277
80. EPMA J. 2018 May 22;9(2):125-131. doi: 10.1007/s13167-018-0133-y. eCollection
2018 Jun.
Diabetes care in figures: current pitfalls and future scenario.
Duarte AA(1), Mohsin S(2), Golubnitschaja O(3)(4)(5).
Author information:
(1)Instituto Master de Ensino Presidente Antonio Carlos (IMEPAC), Araguari, Minas
Gerais Brazil.
(2)2CEMBIO, Rhinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany.
(3)3Radiological Clinic, Rheinische Friedrich-Wilhelms-Universität Bonn,
Sigmund-Freud-Str 25, 53105 Bonn, Germany.
(4)4Breast Cancer Research Centre, Rheinische Friedrich-Wilhelms-Universität
Bonn, Bonn, Germany.
(5)5Centre for Integrated Oncology, Cologne-Bonn, Rheinische
Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Diabetes mellitus (DM) epidemic-on a global scale-is a major and snowballing
threat to public health, healthcare systems and economy, due to the cascade of
pathologies triggered in a long-term manner after the DM manifestation. There are
remarkable differences in the geographic disease spread and acceleration of an
increasing DM prevalence recorded. Specifically, the highest initial prevalence
of DM was recorded in the Eastern-Mediterranean region in 1980 followed by the
highest acceleration of the epidemic characterised by 0.23% of an annual increase
resulted in 2.3 times higher prevalence in the year 2014. In contrast, while the
European region in 1980 demonstrated the second highest prevalence, the DM
epidemic developments were kept much better under control compared to all other
regions in the world. Although both non-modifiable and modifiable risk factors
play a role in DM predisposition, cross-sectional investigations recently
conducted amongst elderly individuals demonstrate that ageing as a non-modifiable
risk factor is directly linked to unhealthy lifestyle as a well-acknowledged
modifiable risk factor which, in turn, may strongly promote ageing process
related to DM even in young populations. Consequently, specifically modifiable

risk factors should receive a particular attention in the context of currently
observed DM epidemic prognosed to expand significantly over 600 million of
diabetes-diseased people by the year 2045. The article analyses demographic
profiles of DM patient cohorts as well as the economic component of the
DM-related crisis and provides prognosis for future scenarios on a global scale.
The innovative approach by predictive diagnostics, targeted prevention and
treatments tailored to the person in a suboptimal health condition (before
clinical onset of the disease), as the medicine of the future is the most
prominent option to reverse currently persisting disastrous trends in diabetes
care. The key role of biomedical sciences in the future developments of diabetes
care is discussed.
DOI: 10.1007/s13167-018-0133-y
PMID: 29896313
Conflict of interest statement: Compliance with ethical standardsThe authors
declare that they have no conflict of interest.Patients have not been involved in
the study.No experiments have been performed including patients and/or animals.
81. Int J Health Policy Manag. 2016 Jun 18;5(10):571-573. doi:
10.15171/ijhpm.2016.79.
Diabetes Dictating Policy: An Editorial Commemorating World Health Day 2016.
Takian A(1)(2)(3), Kazempour-Ardebili S(4).
Author information:
(1)Department of Global Health and Public Policy, School of Public Health, Tehran

(2)Department of Health Management and Economics, School of Public Health, Tehran
(3)College of Health and Life Sciences, Brunel University London, Uxbridge, UK.
(4)Diabetes Research Center, Endocrinology and Metabolism Research Institute,
Tehran University of Medical Sciences, Tehran, Iran.
The 21st century is an era of great challenge for humankind; we are combating
terrorism, climate change, poverty, human rights issues and last but not least
non-communicable diseases (NCDs). The burden of the latter has become so large
that it is being recognized by world leaders globally as an area that it is in
need of much greater attention. In light of this concern, the World Health
Organization (WHO) dedicated this year's World Health Day (held on April 7, 2016)
to raising international awareness on diabetes, the fastest growing NCD in the
world. This editorial is an account of the macro politics in place for fighting
diabetes, both internationally and nationally.
© 2016 by Kerman University of Medical Sciences.
DOI: 10.15171/ijhpm.2016.79
PMCID: PMC5042585
82. World J Diabetes. 2017 Jun 15;8(6):249-269. doi: 10.4239/wjd.v8.i6.249.
Diabetes-induced mechanophysiological changes in the small intestine and colon.
Zhao M(1), Liao D(1), Zhao J(1).
Author information:
(1)Mirabella Zhao, Faculty of Health and Medical Sciences, University of

Copenhagen, DK-2200 Copenhagen N, Denmark.
The disorders of gastrointestinal (GI) tract including intestine and colon are
common in the patients with diabetes mellitus (DM). DM induced intestinal and
colonic structural and biomechanical remodeling in animals and humans. The
remodeling is closely related to motor-sensory abnormalities of the intestine and
colon which are associated with the symptoms frequently encountered in patients
with DM such as diarrhea and constipation. In this review, firstly we review
DM-induced histomorphological and biomechanical remodeling of intestine and
colon. Secondly we review motor-sensory dysfunction and how they relate to
intestinal and colonic abnormalities. Finally the clinical consequences of
DM-induced changes in the intestine and colon including diarrhea, constipation,
gut microbiota change and colon cancer are discussed. The final goal is to
increase the understanding of DM-induced changes in the gut and the subsequent
clinical consequences in order to provide the clinicians with a better
understanding of the GI disorders in diabetic patients and facilitates treatments
tailored to these patients.
DOI: 10.4239/wjd.v8.i6.249
PMCID: PMC5483424
PMID: 28694926
Conflict of interest statement: Conflict-of-interest statement: Authors declare
no conflict of interests for this article.
83. Nutr Diabetes. 2018 Sep 7;8(1):48. doi: 10.1038/s41387-018-0055-8.
Diabetes knowledge and its association with the weight status among residents of
Jeddah City, Saudi Arabia.

Kutbi HA(1), Mosli HH(2), Alhasan AH(3), Mosli RH(4).
Author information:
(1)Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King
Abdulaziz University, P.O. Box 80215, Jeddah, 21589, Saudi Arabia.
hkutbi@kau.edu.sa.
(2)Division of Endocrinology & Metabolism, Department of Medicine, Faculty of
Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
(3)College of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
(4)Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King
Abdulaziz University, P.O. Box 80215, Jeddah, 21589, Saudi Arabia.
OBJECTIVE: To examine the association of weight status with level of diabetes
knowledge (symptoms and complications) among residents of Jeddah City, Saudi
Arabia.
METHODS: In a cross-sectional study, a questionnaire assessing sociodemographic
and health characteristics and knowledge about diabetes and its symptoms and
complications was utilized. Data of 3978 adults, 18 years of age or older, were
collected from public mall sites in Jeddah city and surrounding areas.
Participants were divided into three tertiles based on their knowledge scores.
Weight and height were measured following standardized procedures, and body
weight categories were defined based on body mass index (BMI). The association
between weight status and tertiles of diabetes knowledge was examined using
multinomial logistic regression analysis.
RESULTS: Compared to normal-weight participants, participants who were
underweight, overweight, or obese, did not differ with regards to knowledge about
diabetes symptoms. Adjusted models showed that overweight and obese participants
had lower odds of being in the lowest tertile of knowledge about diabetes
complications compared to normal-weight participants (OR: 0.71, 95% CI: 0.58-0.86
and OR: 0.64, 95% CI: 0.51-0.79, respectively). With regards to general knowledge
about diabetes, the knowledge of participants who were underweight did not differ
when compared to normal-weight participants. Overweight and obese participants
had lower odds of being in the lowest tertile of general knowledge about diabetes
compared to normal-weight participants (OR: 0.78, 95% CI: 0.62-0.97 and OR: 0.60,
95% CI: 0.47-0.76, respectively).
CONCLUSIONS: Overweight and obese individuals have better knowledge about
diabetes compared to normal-weight individuals. Public health programs need to
take into account the level of diabetes knowledge and tailor interventions to aid
behavior and lifestyle change.
DOI: 10.1038/s41387-018-0055-8
PMCID: PMC6127130
PMID: 30190526
84. Cent Asian J Glob Health. 2017 Aug 25;6(1):271. doi: 10.5195/cajgh.2017.271.
eCollection 2017.
Diabetes Mellitus Among Adults in Herat, Afghanistan: A Cross-Sectional Study.
Islam Saeed KM(1).
Author information:
(1)Grant and Service Contract Management Unit, Ministry of Public Health, Kabul,
Afghanistan.
Introduction: Diabetes is reaching epidemic levels in Afghanistan. This study
identifies the risk factors associated with diabetes in Herat City, Afghanistan,
and explores the prevalence of previously undiagnosed diabetes.
Methods: A cross-sectional study was conducted using multistage cluster sampling
by adopting the World Health Organization's (WHO) STEPwise approach to
Surveillance (STEPS). We enrolled 1129 participants aged 25-70 years between May
and June of 2015 (47.4% males, 52.6% females). A structured questionnaire was
used for data collection of demographic, socioeconomic, and behavioral factors.
Investigators collected anthropometric measurements and blood samples from study
participants. A multivariable logistic regression model was used to identify
factors associated with diabetes prevalence.
Results: We found that the prevalence of diabetes in Herat City was 9.9% (9.8% in
males and 10.1% in females). Of the 1129 respondents, only 3.3% were previously
diagnosed with diabetes or were under treatment, whereas 6.6% of respondents were
previously undiagnosed. The multivariable analyses showed that age, frequency of
rice consumption, type of cooking oil, and systolic blood pressure were
associated with diabetes.
Conclusions: This is one of the first studies to discuss the high prevalence of
undiagnosed diabetes in Herat, Afghanistan. This study found several modifiable
factors that were associated with diabetes in Herat, Afghanistan. Future
reduction of disease burden should focus on these factors in the development of
the most optimal diabetes prevention programs.
DOI: 10.5195/cajgh.2017.271
PMCID: PMC5675391
PMID: 29138737
85. Clin Infect Dis. 2017 Mar 15;64(6):719-727. doi: 10.1093/cid/ciw836.
Diabetes Mellitus and Latent Tuberculosis Infection: A Systemic Review and
Metaanalysis.
Lee MR(1)(2)(3), Huang YP(3)(4)(5), Kuo YT(3)(6), Luo CH(3), Shih YJ(3), Shu
CC(7), Wang JY(2), Ko JC(1)(2), Yu CJ(2), Lin HH(3).
Author information:
(1)Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu
Branch, Hsin-Chu, Taiwan.
(2)Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
(3)Institute of Epidemiology and Preventive Medicine, College of Public Health,
National Taiwan University, Taiwan.
(4)Department of Physical Medicine and Rehabilitation, National Taiwan University
(5)Department of Physical Medicine and Rehabilitation, National Taiwan University
Hospital Yun-Lin Branch, Yunlin, Taiwan.
(6)Department of Internal Medicine, National Taiwan University Hospital Bei-Hu
Branch, Taiwan.
(7)Department of Traumatology, National Taiwan University Hospital, Taipei,
Taiwan.
Background: Despite the well-documented association between diabetes and active
tuberculosis, evidence of the association between diabetes and latent
tuberculosis infection (LTBI) remains limited and inconsistent.
Methods: We included observational studies that applied either the tuberculin
skin test or the interferon gamma release assay for diagnosis of LTBI and that
provided adjusted effect estimate for the association between diabetes and LTBI.
We searched PubMed and EMBASE through 31 January 2016. The risk of bias of
included studies was assessed using a quality assessment tool modified from the
Newcastle-Ottawa scale.
Results: Thirteen studies (1 cohort study and 12 cross-sectional studies) were
included, involving 38263 participants. The cohort study revealed an increased
but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence
interval [CI], 0.50-38.55). For the cross-sectional studies, the pooled odds
ratio from the random-effects model was 1.18 (95% CI, 1.06-1.30), with a small
statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment
revealed several methodological issues, but the overall direction of biases would
reduce the positive causal association between diabetes and LTBI.

Conclusions: Diabetes was associated with a small but statistically significant
risk for LTBI. Findings from this review could be used to inform future
cost-effectiveness analysis on the impact of LTBI screening programs among
diabetics.
Diseases Society of America.
DOI: 10.1093/cid/ciw836
PMCID: PMC5399944
86. Curr Diab Rep. 2016 Sep;16(9):80. doi: 10.1007/s11892-016-0778-7.
Diabetes Prevention Interventions in Latin American Countries: a Scoping Review.
Heisler M(1)(2)(3)(4), Kaselitz E(5)(6), Rana GK(7), Piette JD(8)(5)(9)(10).
Author information:
(1)Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
mheisler@umich.edu.
(2)Center for Clinical Management Research (CCMR), Ann Arbor Veterans' Affairs
(VA) Healthcare System, 2215 Fuller Rd. (152), Ann Arbor, MI, 48105, USA.
mheisler@umich.edu.
(3)Department of Health Behavior and Health Education, School of Public Health,
University of Michigan, Ann Arbor, MI, USA. mheisler@umich.edu.
(4)Michigan Center for Diabetes Translational Research (MCDTR), University of
Michigan, Ann Arbor, MI, USA. mheisler@umich.edu.
(5)Center for Clinical Management Research (CCMR), Ann Arbor Veterans' Affairs
(VA) Healthcare System, 2215 Fuller Rd. (152), Ann Arbor, MI, 48105, USA.
(6)Global REACH and Department of Medical Education, University of Michigan
Medical School, Ann Arbor, MI, USA.
(7)Taubman Health Sciences Library, University of Michigan, 1135 East Catherine
Street, Ann Arbor, MI, 48109, USA.
(8)Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
(9)Department of Health Behavior and Health Education, School of Public Health,
University of Michigan, Ann Arbor, MI, USA.
(10)Center for Managing Chronic Disease, University of Michigan School of Public
Health, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Public policies, population health initiatives, and targeted behavioral change
interventions for individuals at risk for developing diabetes are all essential
for diabetes prevention in Latin American countries (LACs). This scoping review
examines (1) the current evidence on diabetes prevention policies and
interventions in LACs to identify components of effective diabetes prevention
models in those countries and (2) effective diabetes prevention interventions
targeting Latino populations in the USA to explore possible lessons from these
interventions for LACs. Diabetes prevention programs in LACs evaluated to date
consist of short-term health professional-led face-to-face behavioral counseling
sessions. Intervention components of US-based programs for Latinos that might
benefit diabetes prevention programs in Latin America include (1) deployment of
community health workers ("promotoras") for diabetes screening and delivery of
lifestyle modification programs, (2) multiple modes of program delivery beyond
face-to-face sessions, (3) information technology to automate and enhance program
delivery, (4) leveraging of pre-existing familial relationships to engage in and
sustain lifestyle modifications, and (5) innovative environmental change
strategies such as collaborations with local food stores and markets to promote
healthy behaviors.
DOI: 10.1007/s11892-016-0778-7
PMCID: PMC5180425
87. Health Expect. 2018 Apr;21(2):549-559. doi: 10.1111/hex.12649. Epub 2017 Nov 22.
Diabetes-related complications: Which research topics matter to diverse patients
and caregivers?
Dogba MJ(1)(2), Dipankui MT(1), Chipenda Dansokho S(1), Légaré F(1)(2), Witteman
HO(1)(2)(3).
Author information:
(1)Department of Family and Emergency Medicine, Faculty of Medicine, Laval
University, Quebec City, QC, Canada.
(2)Office of Education and Professional Development, Faculty of Medicine, Laval
(3)Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Centre
[Health of populations and best health practices axis], Quebec City, QC, Canada.
BACKGROUND: Diabetes is a chronic disease with increasing prevalence worldwide.
Although research has improved its treatment and management, little is known
about which research topics matter to people living with diabetes, particularly
among under-represented groups.
OBJECTIVES: To explore the importance of research topics among a diverse range of
people living with any type of diabetes or caring for someone living with any
type of diabetes.
METHODS: We used a convergent mixed-method design with quantitative and
qualitative aspects. We surveyed a national sample of people living with diabetes
and caregivers of people with diabetes, asking them to rate the importance of 10
predetermined important research topics. We also held three focus groups in two
major cities to explore research concerns of people who are under-represented in

research.
RESULTS: 469 adults (57% men, 42% women) in Canada completed the online survey,
indicating that all 10 areas of research mattered to them, with the highest
ratings accorded to preventing and treating kidney, eye and nerve complications.
Fourteen individuals participated in three focus groups and similarly noted the
importance of research on those three complications. Additionally, focus group
participants also noted the importance of research around daily management. No
new topics were identified.
CONCLUSIONS: This study confirmed the importance of research topics among a
population of people living with or caring for someone with diabetes. Findings
from this study were used to inform the vision for Diabetes Action Canada-a
pan-Canadian Strategy for Patient-Oriented Research (SPOR) Network on diabetes
and its complications.
© 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.
DOI: 10.1111/hex.12649
PMCID: PMC5867328
PMID: 29165920
88. Mo Med. 2016 Sep-Oct;113(5):359-360.
Diabetes Update 2016: What Bartleby the Scrivener Can Teach Us About Diabetes
Care.
Semenkovich CF(1).
Author information:
(1)Clay F. Semenkovich, MD, is Chief of the Division of Endocrinology,
Metabolism, and Lipid Research and Irene E. and Michael M. Karl Professor at
Washington University in St. Louis.
PMCID: PMC6139841
PMID: 30228500
89. Diabet Med. 2018 Nov;35(11):1538-1543. doi: 10.1111/dme.13783. Epub 2018 Aug 2.
Diagnosis of erectile dysfunction can be used to improve screening for Type 2
diabetes mellitus.
Carrillo-Larco RM(1)(2), Luza-Dueñas AC(3), Urdániga-Hung M(3), Bernabé-Ortiz
A(1)(3)(4).
Author information:
(1)CRONICAS Centre of Excellence in Chronic Diseases, Universidad Peruana
Imperial College London, London, UK.
(3)School of Medicine, Faculty of Health Sciences, Universidad Peruana de
Ciencias Aplicadas - UPC, Lima, Peru.
AIMS: To assess the diagnostic accuracy of four undiagnosed Type 2 diabetes
mellitus risk scores accounting for erectile dysfunction status.
METHODS: This was a population-based cross-sectional study. Type 2 diabetes was
defined according to a oral glucose tolerance test and self-reported physician
diagnosis. Erectile dysfunction was defined according to the answer to the
question, 'Have you had difficulties obtaining an erection in the last 6 months?'
(yes/no). The risk scores used were the FINDRISC, LA-FINDRISC, American Diabetes
Association score and the Peruvian Risk Score. A Poisson regression model was
fitted to assess the association between Type 2 diabetes and erectile
dysfunction. The area under the receiver-operating characteristic curve was
estimated overall and by erectile dysfunction status.
RESULTS: A total of 799 men with a mean (sd) age of 48.6 (10.7) years were
included in the study. The overall prevalence of Type 2 diabetes was 9.3%.
Compared with healthy men, men with Type 2 diabetes had 2.71 (95% CI 1.57-4.66)
higher chances of having erectile dysfunction. Having excluded men aware of Type
2 diabetes status (N=38), the area under the receiver-operating characteristic
curve of three of the risk scores (not the American Diabetes Association score)
improved among those who had erectile dysfunction in comparison with those who
did not; for example, the area under the receiver-operating characteristic curve
of the LA-FINDRISC score was 89.6 (95% CI 78.7-99.9) in men with erectile
dysfunction and 76.5 (95% CI 68.5-84.4) overall.
CONCLUSIONS: In a population-based study, erectile dysfunction was more common in
men with Type 2 diabetes than in the otherwise healthy men. Screening for
erectile dysfunction before screening for Type 2 diabetes seems to improve the
accuracy of well-known risk scores for undiagnosed Type 2 diabetes.
© 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on
behalf of Diabetes UK.
DOI: 10.1111/dme.13783
PMCID: PMC6221030
PMID: 30028534
90. J Diabetes Sci Technol. 2017 Nov;11(6):1165-1173. doi: 10.1177/1932296817703670.
Epub 2017 Apr 13.

Diagnostic Accuracy of Random ECG in Primary Care for Early, Asymptomatic Cardiac
Autonomic Neuropathy.
Jelinek HF(1)(2), Adam MTP(3), Krones R(4)(5), Cornforth DJ(3).
Author information:
(1)1 Clinical Medicine, Macquarie University, Sydney, Australia.
(2)2 Centre for Research in Complex Systems and School of Community Health,
Charles Sturt University, Albury, Australia.
(3)3 Applied Informatics Research Group, University of Newcastle, Newcastle,
Australia.
(4)4 Rural Clinical School, University of Melbourne, Shepparton, Australia.
(5)5 Wangaratta Cardiology and Respiratory Centre, Wangaratta, Australia.
AIMS: Cardiac autonomic reflex tests (CARTs) are time consuming and require
patient cooperation for detecting cardiac autonomic neuropathy (CAN). Heart rate
variability (HRV) analysis requires less patient cooperation and is quicker to
complete. However the reliability of HRV results as a clinical tool, with respect
to length of recording and accuracy of diagnosis is inconclusive. The current
study investigated the reproducibility associated with varying length of
recording for early CAN (eCAN) assessment.
METHODS: Participants were 68 males, 72 females with average age of 55 for
controls and 63 for early CAN. Inclusion criteria were that participants were
medication free and presented with no comorbidities. ECGs of control and eCAN
were recorded and heart rate changes analyzed with the fast Fourier transform
(FFT) and Lomb-Scargle periodogram (LSP). Ten-second to 5-minute recordings were
extracted from a 15-minute lead-II ECG and accuracy in assessment of eCAN
determined.
RESULTS: The eCAN group was older ( P < .001) and systolic blood pressure was
higher ( P < .01). HDL-cholesterol was also higher in the eCAN group ( P < .05).
HRV analysis showed that both FFT and LSP results were significantly different
between eCAN and control down to a 10-second ECG length for low frequency (LSP: P
= .013, FFT: P = .024) and high frequency (HF-LSP: P = .002, FFT: P = .002)
power. eCAN assessment was optimal down to 90-second recordings with a
sensitivity of 100% and specificity of 29.49%.
CONCLUSION: HRV is suitable for clinical practice from ECG recordings of more
than 90 seconds with high accuracy and repeatability within a session for each
participant.
DOI: 10.1177/1932296817703670
PMCID: PMC5951037
91. BMC Public Health. 2017 Feb 1;17(1):147. doi: 10.1186/s12889-017-4053-x.
Diet, life-style and cardiovascular morbidity in the rural, free living
population of Elafonisos island.
Kapelios CJ(1), Kyriazis I(2), Ioannidis I(2), Dimosthenopoulos C(2),
Hatziagelaki E(2), Liatis S(2); PERSEAS Study Group.
Collaborators: Mpelliotis E, Papadopoulos I, Spanoudi F, Sgouros K, Logothetis D,
Papaneofytou E, Markatos G, Moschakou S, Mpramos D, Konstantatou E, Antonakoudis
G, Nezi M, Kleftaki M, Markozannes G.
Author information:
(1)Hellenic Medical Society for the study of Risk Factors in Vascular Diseases, 8
Iak. Dragatsi Street, 18535, Peiraias, Greece. chriskapel@hotmail.com.
(2)Hellenic Medical Society for the study of Risk Factors in Vascular Diseases, 8
Iak. Dragatsi Street, 18535, Peiraias, Greece.

BACKGROUND: There are about 70 small islands in the Aegean and Ionian Sea, of
less than 300 Km2 and 5000 inhabitants each, comprising a total population of
more than 75,000 individuals with geographical and socioeconomic characteristics
of special interest. The objective of the present study was to assess lifestyle
characteristics and the state of cardiovascular risk of the population of a small
Eastern Mediterranean island, Elafonisos.
METHODS: PERSEAS (Prospective Evaluation of cardiovascular Risk Surrogates in
Elafonisos Area Study) is an ongoing, population-based, longitudinal survey of
cardiovascular risk factors, life-style characteristics and related
morbidity/mortality performed in a small and relatively isolated island of the
Aegean Sea, named Elafonisos. Validated, closed-ended questionnaires for
demographic, socio-economic, clinical and lifestyle characteristics were
distributed and analyzed. The MedDietScore, a validated Mediterranean diet score
was also calculated. In addition, all participants underwent measurement of
anthropometric parameters, blood pressure and a full blood panel for glucose and
lipids.
RESULTS: The analysis included 596 individuals who represented 74.5% of the
target population. The mean age of the population was 49.5 ± 19.6 years and 48.2%
were males. Fifty participants (8.4%) had a history of cardiovascular disease
(CVD). The rates of reported diabetes, hypertension, and hypercholesterolemia
were 7.7%, 30.9% and 30.9% respectively, with screen-detection of each condition
accounting for an additional 4.0%, 12.9%, and 23.3% of cases, respectively. Four
hundred and seven individuals (68.3%) were overweight or obese, 25% reported
being physically inactive and 36.6% were active smokers. The median MedDietScore
was 25 [interquartile range: 6, range 12-47] with higher values significantly
associated with older age, better education, increased physical activity, absence
of history of diabetes and known history of hypercholesterolemia.
CONCLUSIONS: Obesity and traditional risk factors for CVD are highly prevalent
among the inhabitants of a small Mediterranean island. Adherence to the
traditional Mediterranean diet in this population is moderate, while physical
activity is low. There seems to be a need for lifestyle modification programs in

order to reverse the increasing cardiovascular risk trends in rural isolated
areas of the Mediterranean basin.
DOI: 10.1186/s12889-017-4053-x
PMCID: PMC5286858
92. Nutrients. 2018 Sep 30;10(10). pii: E1385. doi: 10.3390/nu10101385.
Dietary Fats and Chronic Noncommunicable Diseases.
Billingsley HE(1), Carbone S(2), Lavie CJ(3).
Author information:
(1)Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298,
USA. hayley.billingsley@vcuhealth.org.
(2)Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298,
USA. salvatore.carbone@vcuhealth.org.
(3)John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University
of Queensland School of Medicine, New Orleans, LA 70121, USA. clavie@ochsner.org.
The role of dietary fat has been long studied as a modifiable variable in the
prevention and treatment of noncommunicable cardiometabolic disease. Once heavily
promoted to the public, the low-fat diet has been demonstrated to be
non-effective in preventing cardiometabolic disease, and an increasing body of
literature has focused on the effects of a relatively higher-fat diet. More
recent evidence suggests that a diet high in healthy fat, rich in unsaturated
fatty acids, such as the Mediterranean dietary pattern, may, in fact, prevent the
development of metabolic diseases such as type 2 diabetes mellitus, but also
reduce cardiovascular events. This review will specifically focus on clinical

trials which collected data on dietary fatty acid intake, and the association of
these fatty acids over time with measured cardiometabolic health outcomes,
specifically focusing on morbidity and mortality outcomes. We will also describe
mechanistic studies investigating the role of dietary fatty acids on
cardiovascular risk factors to describe the potential mechanisms of action
through which unsaturated fatty acids may exert their beneficial effects. The
state of current knowledge on the associations between dietary fatty acids and
cardiometabolic morbidity and mortality outcomes will be summarized and
directions for future work will be discussed.
DOI: 10.3390/nu10101385
PMCID: PMC6213917
PMID: 30274325
93. Public Health Nutr. 2017 Sep;20(13):2277-2288. doi: 10.1017/S1368980017001173.
Epub 2017 Jun 21.
Dietary gap assessment: an approach for evaluating whether a country's food
supply can support healthy diets at the population level.
Kuyper EM(1), Engle-Stone R(2), Arsenault JE(2), Arimond M(2), Adams KP(2), Dewey
KG(2).
Author information:
(1)1University of California,Davis,College of Agricultural and Environmental
Sciences,International Programs Office,Davis,CA,USA.
(2)2University of California,Davis,Program in International and Community
Nutrition,3253 Meyer Hall,One Shields Avenue,Davis,CA 95616,USA.
OBJECTIVE: Dietary diversity, and in particular consumption of nutrient-rich

foods including fruits, vegetables, nuts, beans and animal-source foods, is
linked to greater nutrient adequacy. We developed a 'dietary gap assessment' to
evaluate the degree to which a nation's food supply could support healthy diets
at the population level. Design/Setting In the absence of global food-based
dietary guidelines, we selected the Dietary Approaches to Stop Hypertension
(DASH) diet as an example because there is evidence it prevents diet-related
chronic disease and supports adequate micronutrient intakes. We used the DASH
guidelines to shape a hypothetical 'healthy' diet for the test country of
Cameroon. Food availability was estimated using FAO Food Balance Sheet data on
country-level food supply. For each of the seven food groups in the 'healthy'
diet, we calculated the difference between the estimated national supply (in
kcal, edible portion only) and the target amounts.
RESULTS: In Cameroon, dairy and other animal-source foods were not adequately
available to meet healthy diet recommendations: the deficit was -365 kcal (-1527
kJ)/capita per d for dairy products and -185 kcal (-774 kJ)/capita per d for
meat, poultry, fish and eggs. Adequacy of fruits and vegetables depended on food
group categorization. When tubers and plantains were categorized as vegetables
and fruits, respectively, supply nearly met recommendations. Categorizing tubers
and plantains as starchy staples resulted in pronounced supply shortfalls: -109
kcal (-457 kJ)/capita per d for fruits and -94 kcal (-393 kJ)/capita per d for
vegetables.
CONCLUSIONS: The dietary gap assessment illustrates an approach for better
understanding how food supply patterns need to change to achieve healthier
dietary patterns.
DOI: 10.1017/S1368980017001173
PMCID: PMC5582405
94. Oxid Med Cell Longev. 2018 Mar 26;2018:7487816. doi: 10.1155/2018/7487816.
eCollection 2018.
Dietary Total Antioxidant Capacity and Dietary Polyphenol Intake and Prevalence
of Metabolic Syndrome in Polish Adults: A Nationwide Study.
Zujko ME(1), Waśkiewicz A(2), Witkowska AM(1), Szcześniewska D(2), Zdrojewski
T(3), Kozakiewicz K(4), Drygas W(2)(5).
Author information:
(1)Department of Food Biotechnology, Medical University of Bialystok, Bialystok,
Poland.
(2)Department of Epidemiology, Cardiovascular Disease Prevention and Health
Promotion, Institute of Cardiology, Warsaw, Poland.
(3)Department of Prevention and Education and Department of Hypertension and
Diabetology, Medical University of Gdansk, Gdansk, Poland.
(4)3rd Department of Cardiology, Upper Silesian Centre of Cardiology, Medical
University of Silesia, Katowice, Poland.
(5)Department of Social and Preventive Medicine, Medical University of Lodz,
Lodz, Poland.
Specific classes and subclasses of polyphenols have been studied for their
potential effects on noncommunicable diseases, but studies on association between
dietary polyphenol intake (DPI) and dietary total antioxidant capacity (DTAC) and
MetS (metabolic syndrome) are scarce. Therefore, the aim of this study was to
determine associations between DTAC and DPI and the prevalence of MetS and its
components in the Polish adult population. Subjects (5690) were participants of
the Polish National Multicentre Health Examination Survey (WOBASZ II study)
performed in 2013-2014. MetS was defined according to the International Diabetes
Federation (IDF) and the American Heart Association/National Heart, Lung, and
Blood Institute (AHA/NHLBI) criteria. Daily food consumption was assessed by
24-hour dietary recall. DTAC and DPI were evaluated using the data of food
consumption and antioxidant potential of foods, measured by FRAP (ferric reducing
antioxidant potential) method, and total polyphenol content in foods, measured by
Folin-Ciocalteu assay. Logistic regression models were used to assess the
relationship between DTAC and DPI and MetS and its components. Crude,
age-adjusted, and multivariable-adjusted models were performed. This study
demonstrated that in Polish women, high DPI and high DTAC were significantly
associated with a reduced odds ratio for the prevalence of MetS components, such
as elevated blood pressure and diabetes. In contrast, in men, high DPI and high
DTAC did not have the potential to alleviate MetS components.
DOI: 10.1155/2018/7487816
PMCID: PMC5892227
95. Nutrients. 2018 Aug 3;10(8). pii: E1011. doi: 10.3390/nu10081011.
Different Risk for Hypertension, Diabetes, Dyslipidemia, and Hyperuricemia
According to Level of Body Mass Index in Japanese and American Subjects.
Kuwabara M(1)(2)(3), Kuwabara R(4), Niwa K(5), Hisatome I(6), Smits G(7),
Roncal-Jimenez CA(8), MacLean PS(9), Yracheta JM(10), Ohno M(11), Lanaspa MA(12),
Johnson RJ(13), Jalal DI(14).
Author information:
(1)Department of Cardiology, Toranomon Hospital, Tokyo 105-8470, Japan.
kuwamasa728@gmail.com.
(2)Division of Renal Diseases and Hypertension, School of Medicine, University of
Colorado Denver, Aurora, CO 80045, USA. kuwamasa728@gmail.com.
(3)Cardiovascular Center, St. Luke's International Hospital, Tokyo 104-8560,
Japan. kuwamasa728@gmail.com.
(4)Department of Pediatrics, Nihon University School of Medicine, Tokyo 173-8610,
Japan. remi.kuwabara@gmail.com.
(5)Cardiovascular Center, St. Luke's International Hospital, Tokyo 104-8560,
Japan. kniwa@aol.com.
(6)Division of Regenerative Medicine and Therapeutics, Department of Regenerative
Medicine and Genomic Function, Institute of Regenerative Medicine and
Biofunction, Tottori University Graduate School of Medical Science, Yonago,
Tottori 683-8503, Japan. hisatome@med.tottori-u.ac.jp.
Colorado Denver, Aurora, CO 80045, USA. smits.gerard.j@gmail.com.
Colorado Denver, Aurora, CO 80045, USA. Carlos.Roncal@ucdenver.edu.
(9)Division of Endocrinology, Metabolism and Diabetes, School of Medicine,
University of Colorado Denver, Aurora, CO 80045, USA. Paul.MacLean@ucdenver.edu.
(10)Department of Pharmaceutics, University of Washington, Seattle, WA 98195,
USA. jmy5@uw.edu.
(11)Department of Cardiology, Toranomon Hospital, Tokyo 105-8470, Japan.
minotky@gmail.com.
(12)Division of Renal Diseases and Hypertension, School of Medicine, University
of Colorado Denver, Aurora, CO 80045, USA. Miguel.LanaspaGarcia@ucdenver.edu.
(13)Division of Renal Diseases and Hypertension, School of Medicine, University
of Colorado Denver, Aurora, CO 80045, USA. Richard.Johnson@ucdenver.edu.
(14)Department of Medicine, University of Iowa, Iowa, IA 52242, USA.
diana-jalal@uiowa.edu.
Obesity is a risk factor for hypertension, diabetes mellitus (DM), dyslipidemia,
and hyperuricemia. Here, we evaluated whether the same body mass index (BMI) for
the U.S. population conferred similar metabolic risk in Japan. This was a
cross-sectional analysis involving 90,047 Japanese adults (18⁻85 years) from St.
Luke's International Hospital, Tokyo, Japan and 14,734 adults from National
Health and Nutrition Examination Survey (NHANES) collected in the U.S. We

compared the prevalence of hypertension, DM, dyslipidemia, and hyperuricemia
according to BMI in Japan and the U.S. The prevalence of hypertension, DM, and
dyslipidemia were significantly higher in the U.S. than Japan, whereas the
prevalence of hyperuricemia did not differ between countries. Higher BMI was an
independent risk factor for hypertension, DM, dyslipidemia, and hyperuricemia
both in Japan and in the U.S. after adjusting for age, sex, smoking and drinking
habits, chronic kidney disease, and other cardiovascular risk factors. The BMI
cut-off above which the prevalence of these cardio-metabolic risk factors
increased was significantly higher in the U.S. than in Japan (27 vs. 23 kg/m² for
hypertension, 29 vs. 23 kg/m² for DM, 26 vs. 22 kg/m² for dyslipidemia, and 27
vs. 23 kg/m² for hyperuricemia). Higher BMI is associated with an increased
prevalence of hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and
U.S. The BMI cut-off above which the prevalence of cardio-metabolic risk factors
increases is significantly lower in Japan than the U.S., suggesting that the same
definition of overweight/obesity may not be similarly applicable in both
countries.
DOI: 10.3390/nu10081011
PMCID: PMC6115805
PMID: 30081468
96. Sci Rep. 2018 Apr 19;8(1):6240. doi: 10.1038/s41598-018-24662-y.
Discordance in glycemic categories and regression to normality at baseline in
10,000 people in a Type 2 diabetes prevention trial.
Sampson M(1), Elwell-Sutton T(2), Bachmann MO(2), Clark A(2), Dhatariya KK(3),
Ferns C(3), Howe A(2), John WG(4), Rayman G(5), Swafe L(3), Turner J(3), Pascale
M(3).
Author information:
(1)Norfolk Diabetes Prevention Study (NDPS), Elsie Bertram Diabetes Centre,
Norfolk and Norwich University Hospital NHS Trust, Norwich, UK.
mike.sampson@nnuh.nhs.uk.
(2)Norwich Medical School (NMS), University of East Anglia (UEA), Norwich, UK.
(3)Norfolk Diabetes Prevention Study (NDPS), Elsie Bertram Diabetes Centre,
Norfolk and Norwich University Hospital NHS Trust, Norwich, UK.
(4)Department Clinical Biochemistry, Norfolk and Norwich University Hospital NHS
Trust, Norwich, UK.
(5)Department of Diabetes and Endocrinology, Ipswich General Hospital, Ipswich,
UK.
The world diabetes population quadrupled between 1980 and 2014 to 422 million and
the enormous impact of Type 2 diabetes is recognised by the recent creation of
national Type 2 diabetes prevention programmes. There is uncertainty about how to
correctly risk stratify people for entry into prevention programmes, how
combinations of multiple 'at high risk' glycemic categories predict outcome, and
how the large recently defined 'at risk' population based on an elevated
glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973
people at highest risk of diabetes in our population, and screened 10,000 of
these with paired fasting plasma glucose and HbA1c for randomisation into a very
large Type 2 diabetes prevention trial. Baseline discordance rate between highest
risk categories was 45.6%, and 21.3-37.0% of highest risk glycaemic categories
regressed to normality between paired baseline measurements (median 40 days
apart). Accurate risk stratification using both fasting plasma glucose and HbA1c
data, the use of paired baseline data, and awareness of diagnostic imprecision at
diagnostic thresholds would avoid substantial overestimation of the true risk of
Type 2 diabetes and the potential benefits (or otherwise) of intervention, in
high risk subjects entering prevention trials and programmes.
DOI: 10.1038/s41598-018-24662-y
PMCID: PMC5908912
PMID: 29674706
97. Int J Environ Res Public Health. 2018 Feb 8;15(2). pii: E294. doi:
10.3390/ijerph15020294.
Disease and Economic Burden of Hospitalizations Attributable to Diabetes Mellitus
and Its Complications: A Nationwide Study in Brazil.
Rosa MQM(1), Rosa RDS(2), Correia MG(3), Araujo DV(4), Bahia LR(5), Toscano
CM(6).
Author information:
(1)Internal Medicine Department, State University of Rio de Janeiro, Rio de
Janeiro 20551-030, Brazil. michelleqmrosa@gmail.com.
(2)Social Medicine Department, School of Medicine, Federal University of Rio
Grande do Sul, Porto Alegre 90035-003, Brazil. roger.srosa@gmail.com.
(3)Biostatistics and Bioinformatics Department, National Institute of Cardiology,
Rio de Janeiro 22240-006, Brazil. mgoulart.inc@gmail.com.
Janeiro 20551-030, Brazil. denizarvianna@gmail.com.
Janeiro 20551-030, Brazil. lucianabahia@gmail.com.
(6)Collective Health Department, Federal University of Goiás, Goiânia 75345-000,
Brazil. ctoscano@terra.com.br.
Diabetes is associated with a significant burden globally. The costs of
diabetes-related hospitalizations are unknown in most developing countries. The
aim of this study was to estimate the total number and economic burden of
hospitalizations attributable to diabetes mellitus (DM) and its complications in

adults from the perspective of the Brazilian Public Health System in 2014. Data
sources included the National Health Survey (NHS) and National database of
Hospitalizations (SIH). We considered diabetes, its microvascular (retinopathy,
nephropathy, and neuropathy) and macrovascular complications (coronary heart
disease, cerebrovascular disease, and peripheral arterial disease), respiratory
and urinary tract infections, as well as selected cancers. Assuming that DM
patients are hospitalized for these conditions more frequently that non-DM
individuals, we estimated the etiological fraction of each condition related to
DM, using the attributable risk methodology. We present number, average cost per
case, and overall costs of hospitalizations attributable to DM in Brazil in 2014,
stratified by condition, state of the country, gender and age group. In 2014, a
total of 313,273 hospitalizations due to diabetes in adults were reported in
Brazil (4.6% of total adult hospitalization), totaling (international dollar)
Int$264.9 million. The average cost of an adult hospitalization due to diabetes
was Int$845, 19% higher than hospitalization without DM. Hospitalizations due to
cardiovascular diseases related to diabetes accounted for the higher proportion
of costs (47.9%), followed by microvascular complications (25.4%) and DM per se
(18.1%). Understanding the costs of diabetes and its major complications is
crucial to raise awareness and to support the decision-making process on policy
implementation, also allowing the assessment of prevention and control
strategies.
DOI: 10.3390/ijerph15020294
PMCID: PMC5858363
PMID: 29419786
Conflict of interest statement: The authors declare no conflict of interest. The
founding sponsors had no role in the design of the study; in the collection,
analyses, or interpretation of data; in the writing of the manuscript, and in the
decision to publish the results.

98. Pediatr Diabetes. 2017 May;18(3):167-177. doi: 10.1111/pedi.12521.
DNA methylation and its role in the pathogenesis of diabetes.
Bansal A(1)(2)(3), Pinney SE(1)(2)(4)(5).
Author information:
(1)Center for Research on Reproduction and Women's Health, Perelman School of
Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
(2)Center of Excellence in Environmental Toxicology, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania.
(3)Division of Neonatology, The Children's Hospital of Philadelphia,
Philadelphia, Pennsylvania.
(4)Division of Endocrinology and Diabetes, The Children's Hospital of
Philadelphia, Philadelphia, Pennsylvania.
(5)Department of Pediatrics, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania.
Although the factors responsible for the recent increase in the prevalence of
diabetes worldwide are not entirely known, the morbidity associated with this
disease results in substantial health and economic burden on society. Epigenetic
modifications, including DNA methylation have been identified as one mechanism by
which the environment interacts with the genome and there is evidence that
alterations in DNA methylation may contribute to the increased prevalence of both
type 1 and type 2 diabetes. This review provides a summary of DNA methylation and
its role in gene regulation, and includes descriptions of various techniques to
measure site-specific and genome-wide DNA methylation changes. In addition, we
review current literature highlighting the complex relationship between DNA
methylation, gene expression, and the development of diabetes and related
complications. In studies where both DNA methylation and gene expression changes
were reported, DNA methylation status had a strong inverse correlation with gene
expression, suggesting that this interaction may be a potential future
therapeutic target. We highlight the emerging use of genome-wide DNA methylation
profiles as a biomarker to predict patients at risk of developing diabetes or
specific complications of diabetes. The development of a predictive model that
incorporates both genetic sequencing and DNA methylation data may be an effective
diagnostic approach for all types of diabetes and could lead to additional
innovative therapies.
DOI: 10.1111/pedi.12521
PMCID: PMC5394941
99. Diabetologia. 2017 Sep;60(9):1740-1750. doi: 10.1007/s00125-017-4325-0. Epub 2017
Jun 8.
Early metabolic markers identify potential targets for the prevention of type 2
diabetes.
Peddinti G(1)(2), Cobb J(3), Yengo L(4)(5)(6)(7), Froguel P(4)(5)(6)(8), Kravić
J(9), Balkau B(10), Tuomi T(11)(12)(13), Aittokallio T(11)(14), Groop L(11)(9).
Author information:
(1)Institute for Molecular Medicine Finland (FIMM), Nordic EMBL Partnership for
Molecular Medicine, University of Helsinki, Helsinki, Finland.
gopal.peddinti@vtt.fi.
(2), Tietotie 2, P. O. Box 1000, FIN-02044 VTT, Espoo, Finland.
gopal.peddinti@vtt.fi.
(3)Metabolon Inc., Durham, NC, USA.
(4)CNRS UMR8199, Pasteur Institute of Lille, Lille, France.
(5)European Genomic Institute for Diabetes (EGID), FR-3508, Lille, France.
(6)Lille University, Lille, France.
(7)Institute for Molecular Bioscience, The University of Queensland, Brisbane,
QLD, Australia.
(8)Department of Genomics of Common Disease, School of Public Health, Imperial
College London, Hammersmith Hospital, London, UK.
(9)Lund University Diabetes Center, Lund, Sweden.
(10)CESP, Faculty of Medicine - University Paris-South; Faculty of Medicine -
University Versailles-St Quentin; Inserm U1018, University Paris-Saclay,
Villejuif, France.
(11)Institute for Molecular Medicine Finland (FIMM), Nordic EMBL Partnership for
Molecular Medicine, University of Helsinki, Helsinki, Finland.
(12)Department of Endocrinology, Abdominal Centre, Helsinki University Central
Hospital, Helsinki, Finland.
(13)Folkhalsan Research Center and Research Programs Unit, Diabetes and Obesity,
University of Helsinki, Helsinki, Finland.
(14)Department of Mathematics and Statistics, University of Turku, Turku,
Finland.
AIMS/HYPOTHESIS: The aims of this study were to evaluate systematically the
predictive power of comprehensive metabolomics profiles in predicting the future
risk of type 2 diabetes, and to identify a panel of the most predictive metabolic
markers.
METHODS: We applied an unbiased systems medicine approach to mine metabolite
combinations that provide added value in predicting the future incidence of type
2 diabetes beyond known risk factors. We performed mass spectrometry-based
targeted, as well as global untargeted, metabolomics, measuring a total of 568
metabolites, in a Finnish cohort of 543 non-diabetic individuals from the Botnia
Prospective Study, which included 146 individuals who progressed to type 2

diabetes by the end of a 10 year follow-up period. Multivariate logistic
regression was used to assess statistical associations, and regularised
least-squares modelling was used to perform machine learning-based risk
classification and marker selection. The predictive performance of the machine
learning models and marker panels was evaluated using repeated nested
cross-validation, and replicated in an independent French cohort of 1044
individuals including 231 participants who progressed to type 2 diabetes during a
9 year follow-up period in the DESIR (Data from an Epidemiological Study on the
Insulin Resistance Syndrome) study.
RESULTS: Nine metabolites were negatively associated (potentially protective) and
25 were positively associated with progression to type 2 diabetes. Machine
learning models based on the entire metabolome predicted progression to type 2
diabetes (area under the receiver operating characteristic curve, AUC = 0.77)
significantly better than the reference model based on clinical risk factors
alone (AUC = 0.68; DeLong's p = 0.0009). The panel of metabolic markers selected
by the machine learning-based feature selection also significantly improved the
predictive performance over the reference model (AUC = 0.78; p = 0.00019;
integrated discrimination improvement, IDI = 66.7%). This approach identified
novel predictive biomarkers, such as α-tocopherol, bradykinin hydroxyproline,
X-12063 and X-13435, which showed added value in predicting progression to type 2
diabetes when combined with known biomarkers such as glucose, mannose and
α-hydroxybutyrate and routinely used clinical risk factors.
CONCLUSIONS/INTERPRETATION: This study provides a panel of novel metabolic
markers for future efforts aimed at the prevention of type 2 diabetes.
DOI: 10.1007/s00125-017-4325-0
PMCID: PMC5552834
100. PLoS One. 2016 Dec 20;11(12):e0167859. doi: 10.1371/journal.pone.0167859.

eCollection 2016.
The Eatwell Guide: Modelling the Health Implications of Incorporating New Sugar
and Fibre Guidelines.
Cobiac LJ(1)(2), Scarborough P(2), Kaur A(2), Rayner M(2).
Author information:
(1)Centre for Health Policy, School of Population and Global Health, The
University of Melbourne, Melbourne, Australia.
(2)British Heart Foundation Centre on Population Approaches for Non-Communicable
Disease Prevention, Nuffield Department of Population Health, University of
Oxford, Oxford, United Kingdom.
OBJECTIVE: To model population health impacts of dietary changes associated with
the redevelopment of the UK food-based dietary guidelines (the 'Eatwell Guide').
METHOD: Using multi-state lifetable methods, we modelled the impact of dietary
changes on cardiovascular disease, diabetes and cancers over the lifetime of the
current UK population. From this model, we determined change in life expectancy
and disability-adjusted life years (DALYs) that could be averted.
RESULTS: Changing the average diet to that recommended in the new Eatwell Guide,
without increasing total energy intake, could increase average life expectancy by
5.4 months (95% uncertainty interval: 4.7 to 6.2) for men and 4.0 months (3.4 to
4.6) for women; and avert 17.9 million (17.6 to 18.2) DALYs over the lifetime of
the current population. A large proportion of the health benefits are from
prevention of type 2 diabetes, with 440,000 (400,000 to 480,000) new cases
prevented in men and 340,000 (310,000 to 370,000) new cases prevented in women,
over the next ten years. Prevention of cardiovascular diseases and colorectal
cancer is also large. However, if the diet recommended in the new Eatwell Guide
is achieved with an accompanying increase in energy intake (and thus an increase
in body mass index), around half the potential improvements in population health
will not be realised.
CONCLUSIONS: The dietary changes required to meet recommendations in the Eatwell
Guide, which include eating more fruits and vegetables and less red and processed
meats and dairy products, are large. However, the potential population health
benefits are substantial.
PMCID: PMC5173361
Conflict of interest statement: PS, AK and MR received funding from Public Health
England during the conduct of the study. LC, PS and MR report grants from the
British Heart Foundation. This does not alter our adherence to PLOS ONE policies
on sharing data and materials.
101. Front Public Health. 2018 Sep 19;6:252. doi: 10.3389/fpubh.2018.00252.
eCollection 2018.
Effect of a Health Coach Intervention for the Management of Individuals With Type
2 Diabetes Mellitus in China: A Pragmatic Cluster Randomized Controlled Trial.
Chapman A(1)(2)(3), Browning CJ(3)(4), Enticott JC(5)(6), Yang H(3)(5), Liu S(7),
Zhang T(8), Thomas SA(3)(4).
Author information:
(1)School of Nursing and Midwifery and Centre for Quality and Patient Safety
Research, Deakin University, Geelong, VIC, Australia.
(2)Monash Health, Clayton, VIC, Australia.
(3)International Institute for Primary Health Care Research, Shenzhen, China.
(4)Research School of Population Health, Australian National University, Acton,

ACT, Australia.
(5)School of Primary and Allied Health Care, Monash University, Notting Hill,
VIC, Australia.
(6)School of Clinical Sciences, Monash University, Dandenong, VIC, Australia.
(7)Key Laboratory of Carcinogenesis and Translational Research, Beijing Office
for Cancer Prevention and Control, Peking University Cancer Hospital and
Institute, Beijing, China.
(8)School of Public Health, Peking University Health Science Centre, Beijing,
China.
Aim: To determine the effect of a health coach intervention for the management of
glycemic control, as well as physiological, psychological and self-care outcomes
of patients with type 2 diabetes mellitus (T2DM), compared with usual care.
Methods: This pragmatic cluster RCT was conducted in the Fengtai district of
Beijing from August 2011 to December 2013. Forty-one community health stations
(CHSs) were cluster randomized (stratified geographically, 1:1 ratio) and
eligible, randomly selected T2DM patients were sequentially contacted by CHSs.
Control participants received usual care according to the Chinese Guideline for
Diabetes Prevention and Management. Intervention participants received 18-months
of health coaching based on principles of Motivational Interviewing (MI) plus
usual care. Medical and pathology fees were waived for both groups. Outcome
assessment was performed at baseline, 6, 12, and 18-months. The primary outcome
was glycated hemoglobin (HbA1c); secondary outcomes encompassed a suite of
physiological, psychological and self-care measures. Results: No differential
treatment effect was found at 18-months for HbA1c (adj. difference -0.07, 95% CI
-0.53 to 0.39, p = 0.769) or any specified secondary outcomes. Interestingly,
both groups displayed a statistically and clinically significant within-group
improvement of the same magnitude at 18-months for HbA1c (intervention: mean
change -3.65, 95% CI -3.92 to -3.37; control: mean change -3.38, 95% CI -3.67 to
-3.08). Conclusions: The lack of differential treatment effects observed indicate
that it may be premature to recommend the routine delivery of health coach

interventions based on MI principles for the management of T2DM in China.
However, the large, comparable within-group improvement in mean HbA1c promotes
the establishment of free, regular clinical health assessments for individuals
with T2DM in China.TRIAL REGISTRATION: ISRCTN registry - ISRCTN01010526
(https://doi.org/10.1186/ISRCTN01010526).
DOI: 10.3389/fpubh.2018.00252
PMCID: PMC6156528
PMID: 30283767
102. Sci Rep. 2018 May 23;8(1):8045. doi: 10.1038/s41598-018-25755-4.
Effect of physical activity on pulse wave velocity in elderly subjects with
normal glucose, prediabetes or Type 2 Diabetes.
Metsämarttila E(1), Rodilla E(2)(3), Jokelainen J(4), Herrala S(4), Leppäluoto
J(1), Keinänen-Kiukaanniemi S(4)(5), Herzig KH(6)(7)(8).
Author information:
(1)Research Unit of Biomedicine, and Biocenter of Oulu, Oulu University, 90014,
Oulu, Finland.
(2)Hypertension Clinic, Internal Medicine, Hospital de Sagunto, Valencia, Spain.
(3)Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain.
(4)Center for Life Course Epidemiology and Systems Medicine, Faculty of Medicine,
University of Oulu, 90014, Oulu, Finland.
(5)Oulu University Hospital, Unit of General Practice, and Health Center of Oulu,
Oulu, Finland.
Oulu, Finland. Karl-Heinz.Herzig@oulu.fi.
(7)Department of Gastroenterology and Metabolism, Poznan University of Medical

Sciences, Poznan, Poland. Karl-Heinz.Herzig@oulu.fi.
(8)Medical Research Center (MRC) and University Hospital, Oulu, Finland.
Karl-Heinz.Herzig@oulu.fi.
Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness,
predicting cardiovascular disease. We hypothesized that the amount of physical
activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic
(T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the
analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral
glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was
registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV
values in subjects with impaired glucose metabolism (IGM) and T2D were higher
than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and
HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not.
The 2 h glucose, heart rate and alcohol consumption in T2D subjects had
independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were
significantly associated to (cf)PWV. Interestingly, lipids did not have an
additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had
0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of
T2D, elevated heart rate and alcohol consumption in males were associated with
increased aortic stiffening in elderly subjects.
DOI: 10.1038/s41598-018-25755-4
PMCID: PMC5966452
PMID: 29795274
103. Sleep Sci. 2017 Apr-Jun;10(2):68-72. doi: 10.5935/1984-0063.20170012.
Effect of yoga and aerobics exercise on sleep quality in women with Type 2
diabetes: a randomized controlled trial.

Ebrahimi M(1), Guilan-Nejad TN(1), Pordanjani AF(1).
Author information:
(1)Department of Sports Sciences, Semnan University, Semnan, Iran.
OBJECTIVE: The aim of this study was investigating the effect of 12 weeks of yoga
and aerobic exercise (running on a treadmill) on the sleep quality in women with
Type 2 diabetes.
MATERIALS AND METHODS: 39 diabetic women were selected from Semnan city with the
mean age of 46.85±3.35 years, weight of 69.79±17.18 kg, height of 155.03±5.00,
BMI of 29.64±5.00 kg/m2 who had a background of diabetes for 6.46±2.69 years.
They were then randomly divided into yoga exercise (n=15), aerobic exercise
(n=13), and control group (n=11). The exercise program was performed for 12
weeks, three sessions per each week. In order to measure the sleep quality, the
Pittsburgh Sleep Quality Index (PSQI) was used. The data were analyzed by
non-parametric wilcoxon and Kruskal-Wallis Test at significance level of p<0.05.
RESULTS: Overall score of sleep quality improved after six (p=0.001) and 12
(p=0.001) weeks of yoga exercise. Also, significant effect was observed after 6
weeks of aerobic exercise (p=0.039). However, the positive effect was diminished
to under significant levels after 12 weeks of aerobic exercise (p=0.154).
Kruskal-Wallis Test showed significant differences between yoga and aerobic
groups after 12 weeks of exercise (p=0.002). No significant differences were
observed in control groups in all situation.
CONCLUSIONS: It can be concluded that yoga exercise is more effective in
improving the sleep quality in comparison with the same course of aerobic
exercise in women suffering from diabetes Type 2. Thus, yoga exercise can be
suggested to these patients.
DOI: 10.5935/1984-0063.20170012
PMCID: PMC5612039
PMID: 28966742
104. Diabetes Ther. 2018 Apr;9(2):583-612. doi: 10.1007/s13300-018-0373-9. Epub 2018
Feb 7.
Effectiveness and Safety of a Novel Care Model for the Management of Type 2
Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.
Hallberg SJ(1)(2), McKenzie AL(3), Williams PT(4), Bhanpuri NH(2), Peters AL(5),
Campbell WW(6), Hazbun TL(1), Volk BM(2), McCarter JP(2)(7), Phinney SD(2), Volek
JS(2)(8).
Author information:
(1)Medically Supervised Weight Loss, Indiana University Health Arnett, Lafayette,
IN, USA.
(2)Virta Health, San Francisco, CA, USA.
(3)Virta Health, San Francisco, CA, USA. amy@virtahealth.com.
(4)Independent Consultant, Lafayette, CA, USA.
(5)Keck School of Medicine, University of Southern California, Los Angeles, CA,
USA.
(6)Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
(7)Department of Genetics, Washington University School of Medicine, St. Louis,
MO, USA.
(8)Department of Human Sciences, The Ohio State University, Columbus, OH, USA.
Erratum in
Diabetes Ther. 2018 Mar 5;:.
INTRODUCTION: Carbohydrate restriction markedly improves glycemic control in
patients with type 2 diabetes (T2D) but necessitates prompt medication changes.
Therefore, we assessed the effectiveness and safety of a novel care model
providing continuous remote care with medication management based on biometric
feedback combined with the metabolic approach of nutritional ketosis for T2D
management.
METHODS: We conducted an open-label, non-randomized, controlled, before-and-after
1-year study of this continuous care intervention (CCI) and usual care (UC).
Primary outcomes were glycosylated hemoglobin (HbA1c), weight, and medication
use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR,
blood lipids and lipoproteins, liver and kidney function markers, and
high-sensitivity C-reactive protein (hsCRP).
RESULTS: 349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years,
116.5 (25.9) kg, 40.4 (8.8) kg m2, 92% obese, 88% prescribed T2D medication]; UC:
n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m2, 82% obese, 87%
prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI
at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA1c
declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol-1 (7.6 ± 0.09% to 6.3 ± 0.07%,
P < 1.0 × 10-16), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10-16), and T2D
medication prescription other than metformin declined from 56.9 ± 3.1% to
29.7 ± 3.0% (P < 1.0 × 10-16). Insulin therapy was reduced or eliminated in 94%
of users; sulfonylureas were entirely eliminated in the CCI. No adverse events
were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR - 55%
(P = 3.2 × 10-5), hsCRP - 39% (P < 1.0 × 10-16), triglycerides - 24%
(P < 1.0 × 10-16), HDL-cholesterol + 18% (P < 1.0 × 10-16), and LDL-cholesterol
+ 10% (P = 5.1 × 10-5); serum creatinine and liver enzymes (ALT, AST, and ALP)
declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC
participants had no significant changes in biomarkers or T2D medication
prescription at 1 year.
CONCLUSIONS: These results demonstrate that a novel metabolic and continuous
remote care model can support adults with T2D to safely improve HbA1c, weight,
and other biomarkers while reducing diabetes medication use. CLINICALTRIALS.
GOV IDENTIFIER: NCT02519309.

FUNDING: Virta Health Corp.
DOI: 10.1007/s13300-018-0373-9
PMCID: PMC6104272
PMID: 29417495
105. Diabetol Metab Syndr. 2018 Sep 3;10:67. doi: 10.1186/s13098-018-0368-8.
eCollection 2018.
Effectiveness of educational intervention based on psychological factors on
achieving health outcomes in patients with type 2 diabetes.
Salahshouri A(1), Zamani Alavijeh F(2), Mahaki B(3)(4), Mostafavi F(2).
Author information:
(1)1Student Research Committee, School of Health, Isfahan University of Medical
Sciences, Isfahan, Iran.
(2)2Department of Health Education and Promotion, School of Health, Isfahan
University of Medical Sciences, Isfahan, 8174673461 Iran.
(3)3Department of Biostatistics, School of Health, Kermanshah University of
Medical Sciences, Kermanshah, Iran.
(4)4Department of Biostatistics, School of Health, Isfahan University of Medical
Sciences, Isfahan, Iran.
Background: Managing type 2 diabetes (T2D) is assumed to be heavily dependent on
patients' active participation in their own self-care behaviors including
prescribed diets.
Objectives: The purpose of the present study was to investigate the effectiveness
of educational intervention based on psychological factors on nutritional
behaviors as well as levels of fasting blood sugar (FBS) and glycated hemoglobin
(HbA1c) in patients with T2D referring to diabetes clinics and healthcare centers
in the city of Izeh, Iran.
Methods: A total number of 145 patients were recruited in this clinical trial and
then randomly assigned to two groups of intervention (n = 73 individuals) and
control (n = 72 individuals). After that, a researcher-made multi-part
questionnaire including a demographic characteristics information form, a
nutritional perceptions and beliefs questionnaire; a scale measuring fears,
concerns, and discomforts associated with diabetic diet, as well as the valid and
reliable Perceived Dietary Adherence Questionnaire were used to collect the
required data before and 3 months after the completion of the educational
intervention. To this end, the patients in the intervention group attended an
educational program for eight sessions but the individuals in the control group
only received routine services. Data analysis was also conducted using the SPSS
Statistics (Version 18) and via descriptive and inferential statistics.
Results: The findings revealed that the mean scores of the sub-groups of
nutritional perceptions and beliefs (but not exaggerated ones) in the patients
assigned to the intervention group were significantly higher than those in the
control group after 3 months (p = 0.001). As well, the mean scores of the
sub-groups of fears, concerns, and discomforts in patients as well as exaggerated
beliefs witnessed a significant decrease in the intervention group compared to
those in the control group (p = 0.001) 3 months after the educational
intervention. Furthermore, the mean scores of adherence to a healthy diet in the
intervention group had significantly increased compared to those in the control
group. There was correspondingly a significant descending trend in the average
levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) in the
intervention group compared to those obtained in the control group (p = 0.001).
Conclusion: The results of this study shed light on the importance of the
effectiveness of psychological factors on achieving health outcomes in patients
with type 2 diabetes (T2D). Moreover, a new combination of diet-related
psychological factors in patients with diabetes was introduced in the present
study.Trial registration IRCT. IRCT20180308039008N1. Registered 15 April 2018,

http://www.irct.ir.
DOI: 10.1186/s13098-018-0368-8
PMCID: PMC6122479
PMID: 30186372
106. J Diabetes Res. 2017;2017:5282343. doi: 10.1155/2017/5282343. Epub 2017 Aug 24.
Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three
Korean Observational Studies (the VICTORY Study).
Suh S(1), Song SO(2), Kim JH(3), Cho H(4), Lee WJ(5), Lee BW(6).
Author information:
(1)Division of Endocrinology, Dong-A University Medical Center, Dong-A University
School of Medicine, Busan, Republic of Korea.
(2)Division of Endocrinology, Department of Internal Medicine, National Health
Insurance Service, Ilsan Hospital, Ilsan, Republic of Korea.
(3)Division of Endocrinology and Metabolism, Department of Medicine, Samsung
Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of
Korea.
(4)Novartis Korea, Seoul, Republic of Korea.
(5)Department of Internal Medicine, Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Republic of Korea.
(6)Division of Endocrinology and Metabolism, Department of Internal Medicine,
Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of
Korea.
The present observational study aimed to evaluate the clinical effectiveness of
vildagliptin with metformin in Korean patients with type 2 diabetes mellitus

(T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the
vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective
observational study of vildagliptin/metformin (fixed DC or free DC). The
effectiveness endpoint was the proportion of patients who achieved a glycemic
target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the
analysis; of these, 2087 patients were eligible. The mean patient age was
56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0%
at 24 weeks. The glycemic target achievement rate was significantly greater in
patients with baseline HbA1c < 7.5% versus ≥7.5% (84.64% versus 43.97%),
receiving care at the hospital versus clinic (67.95% versus 52.33%), and
receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%).
Multivariate logistic regression analysis indicated that disease duration (P <
0.0001), baseline HbA1c (P < 0.0001), and DC type (P = 0.0103) had significant
effects on drug effectiveness. Vildagliptin plus metformin appeared as an
effective treatment option for patients with T2DM in clinical practice settings
in Korea.
DOI: 10.1155/2017/5282343
PMCID: PMC5613692
eCollection 2018.
The effects of an acute exercise bout on GH and IGF-1 in prediabetic and healthy
African Americans: A pilot study investigating gene expression.
Berry NT(1), Hubal M(2)(3), Wideman L(1).
Author information:
(1)University of North Carolina at Greensboro, Greensboro, NC, United States of
America.
(2)George Washington University Milken Institute School of Public Health,
Washington, D.C., United States of America.
(3)Children's National Medical Center, NW, Washington, D.C., United States of
America.
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a
worldwide epidemic. African American (AA) individuals are disproportionately more
likely to become diabetic than other ethnic groups. Over the long-term, metabolic
complications related to diabetes result in significant alterations in growth
hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited
exercise-related studies in the area of gene expression changes with disease
progression, the objective of this study was to examine differences in
exercise-induced gene expression related to the GH and IGF-1 pathways in
peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA
individuals.DESIGN: Ten subjects [5 PD (age = 35±9.3 yr, BMI = 32.1±4.0, FBG =
101.8±1.3 mg/dl) and 5 CON (age = 31±9.4 yr, BMI = 29.4±5.2, FBG = 82.8±9.7
mg/dl)] had blood drawn for RNA isolation prior to exercise (Pre), immediately
following acute moderate intensity exercise on a treadmill (Post-1), 6-hours post
(Post-6), and 24-hours post (Post-24). Isolation of mRNA from PBMCs was performed
using ficoll separation, while the profiling of mRNA expression was performed
using Illumina beadchip arrays with standard protocols. Scan results were
statistically analyzed for a specific list of genes related to GH and IGF-1. GH
and IGF-1 protein levels were also assessed in each sample. To address issues of
normality, all GH and IGF-1 data were log-transformed prior to analysis.
Statistical significance was set at p<0.05.
RESULTS: Group differences for GH2 variant 2 (p = 0.070) and GH2 variant 3 (p =
0.059) were coupled with significant alterations in IGF-1 mRNA over time (p =
0.024). A significant interaction between group and time was observed for GHRH
mRNA (p = 0.008). No group differences were observed in GH AUC (p = 0.649), ΔGH

(p = 0.331), GHrec (p = 0.294), or IGF-1 AUC (p = 0.865), representing a similar
exercise-induced GH and IGF-1 response for both groups.
CONCLUSIONS: Analysis of GH and IGF-1 related-gene expression indicates that mild
elevations in fasting blood glucose and exercise-induced alterations in gene
expression are impacted by the prediabetic state.
PMCID: PMC5774763
108. J Appl Oral Sci. 2018 Jul 10;26:e20180083. doi: 10.1590/1678-7757-2018-0083.
Effects of hyperbaric oxygen treatment on implant osseointegration in
experimental diabetes mellitus.
Altug HA(1), Tatli U(2), Coskun AT(1), Erdogan Ö(3), Özkan A(1), Sencimen M(1),
Kürkçü M(2).
Author information:
(1)University of Health Sciences, Gülhane Faculty of Dentistry, Department of
Oral and Maxillofacial Surgery, Ankara, Turkey.
(2)Cukurova University, Faculty of Dentistry, Department of Oral and
Maxillofacial Surgery, Adana, Turkey.
(3)Okan University, Faculty of Dentistry, Department of Oral and Maxillofacial
Surgery, Istanbul, Turkey.
OBJECTIVE: To evaluate whether hyperbaric oxygen (HBO) treatment has a favorable
effect on implant osseointegration in diabetic rabbits.
MATERIAL AND METHODS: An experimental diabetes model was induced in 32 New
Zealand rabbits through IV injection of alloxan. After the state of diabetes had
been confirmed, one dental implant was placed in the metaphysical region of each
animal's tibia. After the implants' placements, the animals were divided into two
groups. Half of the animals underwent HBO treatment, while the other group did
not receive HBO treatment and served as the control group. The animals were
euthanized at the 4th and 8th weeks. The osseointegration of the implants were
compared by histomorphometry and resonance frequency analysis (RFA).
RESULTS: The Bone Implant Contact (BIC) values were significantly higher in the
HBO group than in the control group at the 4th week. There was no difference in
the BIC values between the groups at the 8th week. There was no significant
difference in the RFA scores between the groups both at the 4th and 8th weeks
after the operation.
CONCLUSION: Histomorphometry findings suggest that HBO has positive effect on
implant osseointegration in the early healing period in diabetic rabbits.
However, implant stability is not affected by HBO treatment.
DOI: 10.1590/1678-7757-2018-0083
PMCID: PMC6025889
109. Int J Mol Sci. 2018 Apr 10;19(4). pii: E1132. doi: 10.3390/ijms19041132.
The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker
Diabetic Fatty Rats: The Role of HO-1.
Csepanyi E(1)(2), Czompa A(3), Szabados-Furjesi P(4)(5), Lekli I(6), Balla J(7),
Balla G(8), Tosaki A(9), Bak I(10)(11).
Author information:
(1)Department of Bioanalytical Chemistry, Faculty of Pharmacy, University of
Debrecen, 4032 Debrecen, Hungary. csepanyi.evelin@pharm.unideb.hu.

(2)Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, 4032
Debrecen, Hungary. csepanyi.evelin@pharm.unideb.hu.
Debrecen, Hungary. czompa.attila@pharm.unideb.hu.
Debrecen, 4032 Debrecen, Hungary. szabados-furjesi.peter@pharm.unideb.hu.
Debrecen, Hungary. szabados-furjesi.peter@pharm.unideb.hu.
Debrecen, Hungary. lekli.istvan@pharm.unideb.hu.
(7)Hemostasis, Thrombosis and Vascular Biology Research Group, Hungarian of
Academy of Sciences, 4032 Debrecen, Hungary. balla.jozsef@med.unideb.hu.
(8)Hemostasis, Thrombosis and Vascular Biology Research Group, Hungarian of
Academy of Sciences, 4032 Debrecen, Hungary. balla@med.unideb.hu.
Debrecen, Hungary. tosaki.arpad@pharm.unideb.hu.
Debrecen, 4032 Debrecen, Hungary. bak.istvan@pharm.unideb.hu.
Debrecen, Hungary. bak.istvan@pharm.unideb.hu.
Nowadays, there is a growing interest in compounds derived from plants as
potential raw materials for drug development. One of the most studied compounds
is beta-carotene (BC). Several clinical studies can be found investigating the
cardiovascular effects of BC, however, all these results are controversial. There
is an increasing body of evidence showing that besides the well-known antioxidant
properties, under strong oxidative circumstances, BC could become prooxidant as
well. In this study, we investigated the effects of long-term, low- and high-dose
BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from Zucker
diabetic fatty (ZDF) rats. The animals were treated with various daily doses of
BC for 4 weeks and then hearts were isolated and subjected to 30 min of global
ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels
were measured before, after two weeks, and at the end of the treatment. In
isolated hearts, the myocardial function was registered. At the end of the
reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression
were measured. The results showed that a low dose of BC treatment significantly
improved postischemic recovery, which was reflected in a decreased IS.
Interestingly, when BC was applied at high concentrations, the observed
protective effects were lost. Although BC treatment increased HO-1 expression, we
did not observe a better heart function and/or decreased IS in the
high-dose-treated group. Glucose tolerance tests showed a
concentration-independent decrease in blood glucose levels. Our results suggest
that long-term, low-dose BC treatment could be effective in the treatment of
type-2-diabetes and related cardiovascular diseases.
DOI: 10.3390/ijms19041132
PMCID: PMC5979408
110. PLoS Med. 2016 Jul 19;13(7):e1002087. doi: 10.1371/journal.pmed.1002087.
eCollection 2016 Jul.
Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and
Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and
Meta-analysis of Randomised Controlled Feeding Trials.
Imamura F(1), Micha R(2), Wu JH(3), de Oliveira Otto MC(4), Otite FO(5), Abioye
AI(6), Mozaffarian D(2).

Author information:
(1)Medical Research Council Epidemiology Unit, Institute of Metabolic Science,
University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus,
Cambridge, United Kingdom.
(2)Tufts Friedman School of Nutrition Science & Policy, Boston, Massachusetts,
United States of America.
(3)George Institute for Global Health, The University of Sydney, Sydney Medical
School, Camperdown, Australia.
(4)Department of Epidemiology, Human Genetics & Environmental Sciences, The
University of Texas Health Science Center at Houston, Houston, Texas, United
States of America.
(5)Department of Neurology, University of Miami Miller School of Medicine/Jackson
Memorial Hospital, Miami, Florida, United States of America.
(6)Department of Global Health and Population, Harvard T. H. Chan School of
Public Health, Boston, Massachusetts, United States of America.
BACKGROUND: Effects of major dietary macronutrients on glucose-insulin
homeostasis remain controversial and may vary by the clinical measures examined.
We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA),
polyunsaturated fat (PUFA), and carbohydrate affect key metrics of
glucose-insulin homeostasis.
METHODS AND FINDINGS: We systematically searched multiple databases (PubMed,
EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE,
Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015
that tested effects of macronutrient intake on blood glucose, insulin, HbA1c,
insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded
trials with non-isocaloric comparisons and trials providing dietary advice or
supplements rather than meals. Studies were reviewed and data extracted
independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet
arms and 4,220 adults, met eligibility requirements. Using multiple-treatment
meta-regression, we estimated dose-response effects of isocaloric replacements

between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and
dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant
effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99),
but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing
carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h
post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model
assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30).
Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17,
-0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA
significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard
acute insulin response in ten trials, PUFA significantly improved insulin
secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate,
SFA, or even MUFA. No significant effects of any macronutrient replacements were
observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model
index). Limitations included a small number of trials for some outcomes and
potential issues of blinding, compliance, generalisability, heterogeneity due to
unmeasured factors, and publication bias.
CONCLUSIONS: This meta-analysis of randomised controlled feeding trials provides
evidence that dietary macronutrients have diverse effects on glucose-insulin
homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent
favourable effects were seen with PUFA, which was linked to improved glycaemia,
insulin resistance, and insulin secretion capacity.
DOI: 10.1371/journal.pmed.1002087
PMCID: PMC4951141
111. J Diabetes Res. 2018 Feb 18;2018:1082561. doi: 10.1155/2018/1082561. eCollection
2018.
The Effects of Sleeve Gastrectomy on Glucose Metabolism and Glucagon-Like Peptide
1 in Goto-Kakizaki Rats.
Li L(1)(2), Wang X(2), Bai L(2), Yu H(1)(2), Huang Z(1)(3), Huang A(4), Luo
Y(1)(2), Wang J(1)(2).
Author information:
(1)Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen
University, Guangzhou, China.
(2)Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory
of Colorectal and Pelvic Floor Disease, Guangzhou, China.
(3)Department of Biochemistry and Molecular Medicine, University of California,
Davis, Sacramento, CA, USA.
(4)Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun
Yat-sen University, Guangzhou, China.
Purpose: To investigate the effects of sleeve gastrectomy (SG) on glucose
metabolism and changes in glucagon-like peptide 1 (GLP-1) in Goto-Kakizaki (GK)
rats.
Methods: GK rats were randomly assigned to one of three groups: SG, SG pair-fed
plus sham surgery (PF-sham), and ad libitum-fed no surgery (control). Food
intake, body weight, blood glucose, GLP-1 and insulin levels, and GLP-1
expression in the jejunum and ileum were compared.
Results: The SG rats exhibited lower postoperative food intake, body weight, and
fasting glucose than did the control rats (P < 0.05). SG significantly improved
glucose and insulin tolerance (P < 0.05). Plasma GLP-1 levels were higher in SG
rats than in control or PF-sham rats in the oral glucose tolerance test (OGTT) (P
< 0.05). Blood glucose levels expressed as a percentage of baseline were higher
in SG rats than in control rats after exendin (9-39) administration (P < 0.05).
The levels of GLP-1 expression in the jejunum and ileum were higher in SG rats
than in PF-sham and control rats (P < 0.05).

Conclusions: Improvement of glucose metabolism by SG was associated with
increased GLP-1 secretion. SG contributes to an increase in plasma GLP-1 levels
via increased GLP-1 expression in the mucosa of the jejunum and/or ileum.
DOI: 10.1155/2018/1082561
PMCID: PMC5835276
112. Adv Ther. 2018 Mar;35(3):367-381. doi: 10.1007/s12325-018-0668-2. Epub 2018 Feb
27.
Efficacy and Safety of GPR119 Agonist DS-8500a in Japanese Patients with Type 2
Diabetes: a Randomized, Double-Blind, Placebo-Controlled, 12-Week Study.
Yamada Y(1), Terauchi Y(2), Watada H(3), Nakatsuka Y(4), Shiosakai K(5), Washio
T(6), Taguchi T(7).
Author information:
(1)Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University
Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
(2)Department of Endocrinology and Metabolism, Yokohama City University Graduate
School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004,
Japan.
(3)Department of Metabolism & Endocrinology, Juntendo University Graduate School
of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
(4)Clinical Development Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi,
Shinagawa-ku, Tokyo, 140-8710, Japan.
(5)Biostatistics & Data Management, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi,
(6)Asia Development Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi,

(7)Clinical Development Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi,
Shinagawa-ku, Tokyo, 140-8710, Japan. taguchi.takashi.ft@daiichisankyo.co.jp.
INTRODUCTION: G protein-coupled receptor 119 (GPR119) is a promising target for
the treatment of type 2 diabetes mellitus (T2DM), as both insulin and
glucagon-like peptide-1 secretion can be promoted with a single drug. We compared
the efficacy and safety of the GPR119 agonist DS-8500a with placebo and
sitagliptin 50 mg in Japanese patients with T2DM.
METHODS: This randomized, double-blind, parallel-group comparison study was
conducted in Japan (trial registration NCT02628392, JapicCTI-153068). Eligible
patients aged ≥ 20 years with T2DM and hemoglobin A1c (HbA1c) ≥ 7.0% and < 10.0%
were randomized to receive placebo, DS-8500a (25, 50, or 75 mg), or sitagliptin
50 mg once daily for 12 weeks. The primary efficacy endpoint was change in HbA1c
from baseline to week 12. Secondary endpoints included change in fasting plasma
glucose (FPG), glucose AUC0-3h during a meal tolerance test, 2-hour postprandial
glucose (2hr-PPG), and changes in lipid parameters (total, low-density
lipoprotein (LDL-) and high-density lipoprotein (HDL-) cholesterol, and
triglycerides) at week 12. Safety endpoints included adverse events,
hypoglycemia, and clinical/laboratory variables.
RESULTS: DS-8500a demonstrated dose-dependent HbA1c lowering compared with
placebo at week 12: change from baseline - 0.23% (p = 0.0173), - 0.37%
(p = 0.0001), and - 0.44% (p < 0.0001) in the 25-mg, 50-mg, and 75-mg groups,
respectively. At 50- and 75-mg doses, DS-8500a significantly lowered FPG, glucose
AUC0-3h, and 2hr-PPG compared with placebo. The glucose-lowering effect was
maintained up to 12 weeks. DS-8500a did not lower any of the above parameters to
a greater extent than sitagliptin. Compared with placebo and sitagliptin,
DS-8500a 50 and 75 mg significantly reduced total cholesterol, LDL-cholesterol,
and triglycerides, and significantly increased HDL-cholesterol. All DS-8500a
doses were well tolerated. Two cases of clinically relevant drug-related
hypoglycemia occurred in the DS-8500a 50-mg group.

CONCLUSION: DS-8500a was well tolerated and demonstrated significant
glucose-lowering effects and favorable changes in lipid profiles up to 12 weeks
in Japanese patients with T2DM.
FUNDING: Daiichi Sankyo Co. Ltd.
DOI: 10.1007/s12325-018-0668-2
PMCID: PMC5859088
PMID: 29488152
113. J Diabetes Res. 2018 Feb 12;2018:2052101. doi: 10.1155/2018/2052101. eCollection
2018.
Efficacy and Safety of Insulin Glargine 300 U/mL versus 100 U/mL in Diabetes
Mellitus: A Comprehensive Review of the Literature.
Vargas-Uricoechea H(1).
Author information:
(1)Metabolic Diseases Study Group, Division of Endocrinology and Metabolism,
Department of Internal Medicine, Universidad del Cauca, Popayán, Cauca, Colombia.
To achieve good metabolic control in diabetes and maintain it in the long term, a
combination of changes in lifestyle and pharmacological treatment is necessary.
The need for insulin depends upon the balance between insulin secretion and
insulin resistance. Insulin is considered the most effective glucose-lowering
therapy available and is required by people with type 1 diabetes mellitus to
control their blood glucose levels; yet, many people with type 2 diabetes
mellitus will also eventually require insulin therapy, due to the progressive
nature of the disease. A variety of long-acting insulins is currently used for
basal insulin therapy (such as insulin glargine, degludec, and detemir), each
having sufficient pharmacodynamic and pharmacokinetic profiles to afford lower
intrapatient variability and an extended duration of action. The new glargine-300
formulation was developed to have a flatter and more extended time-action profile
than the original glargine-100, and these characteristics may translate into more
stable and sustained glycemic control over a 24 h dosing interval. The objective
of this comprehensive review was to summarize the available evidence on the
clinical efficacy and safety of glargine-300 versus glargine-100 from the EDITION
clinical trial program, in patients with type 1 and type 2 diabetes mellitus.
DOI: 10.1155/2018/2052101
PMCID: PMC5830021
114. Diabetes Metab Syndr Obes. 2016 Nov 4;9:381-390. eCollection 2016.
eHealth technologies to support nutrition and physical activity behaviors in
diabetes self-management.
Rollo ME(1), Aguiar EJ(2), Williams RL(1), Wynne K(3), Kriss M(3), Callister
R(4), Collins CE(1).
Author information:
(1)School of Health Sciences, Faculty of Health and Medicine, Priority Research
Centre for Physical Activity and Nutrition, University of Newcastle, Callaghan,
NSW, Australia.
(2)Department of Kinesiology, School of Public Health and Health Sciences,
University of Massachusetts Amherst, Amherst, MA, USA.
(3)Department of Diabetes and Endocrinology, John Hunter Hospital, Hunter New
England Health, New Lambton, NSW, Australia.
(4)School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine,

Priority Research Centre for Physical Activity and Nutrition, University of
Newcastle, Callaghan, NSW, Australia.
Diabetes is a chronic, complex condition requiring sound knowledge and
self-management skills to optimize glycemic control and health outcomes. Dietary
intake and physical activity are key diabetes self-management (DSM) behaviors
that require tailored education and support. Electronic health (eHealth)
technologies have a demonstrated potential for assisting individuals with DSM
behaviors. This review provides examples of technologies used to support
nutrition and physical activity behaviors in the context of DSM. Technologies
covered include those widely used for DSM, such as web-based programs and mobile
phone and smartphone applications. In addition, examples of novel tools such as
virtual and augmented reality, video games, computer vision for dietary
carbohydrate monitoring, and wearable devices are provided. The challenges to,
and facilitators for, the use of eHealth technologies in DSM are discussed.
Strategies to support the implementation of eHealth technologies within practice
and suggestions for future research to enhance nutrition and physical activity
behaviors as a part of broader DSM are provided.
DOI: 10.2147/DMSO.S95247
PMCID: PMC5104301
PMID: 27853384
Conflict of interest statement: The authors report no conflicts of interest in
this work.
115. BMJ Open Diabetes Res Care. 2017 Jul 19;5(1):e000401. doi:
Elevated incidence rates of diabetes in Peru: report from PERUDIAB, a national

urban population-based longitudinal study.
Seclen SN(1), Rosas ME(2), Arias AJ(3), Medina CA(4).
Author information:
(1)Diabetes, Hypertension and Lipids Unit, Institute of Gerontology, Universidad
Peruana Cayetano Heredia, Lima, Peru.
(2)School of Public Health and Administration, Universidad Peruana Cayetano
(3)Technical Direction of Demography and Social Indicators, National Institute of
Statistics and Informatics, Lima, Peru.
(4)Medical Departament, Sanofi, Lima, Peru.
OBJECTIVE: A recent report from a non-nationally representative, geographically
diverse sample in four separate communities in Peru suggests an unusually high
diabetes incidence. We aimed to estimate the national diabetes incidence rate
using PERUDIAB, a probabilistic, national urban population-based longitudinal
study.
RESEARCH DESIGN AND METHODS: 662 subjects without diabetes, selected by
multistage, cluster, random sampling of households, representing the 24
administrative and the 3 (coast, highlands and jungle) natural regions across the
country, from both sexes, aged 25+ years at baseline, enrolled in 2010-2012, were
followed for 3.8 years. New diabetes cases were defined as fasting blood glucose
≥126 mg/dL or on medical diabetes treatment.
RESULTS: There were 49 cases of diabetes in 2408 person-years follow-up. The
weighted cumulative incidence of diabetes was 7.2% while the weighted incidence
rate was estimated at 19.5 (95% CI 13.9 to 28.3) new cases per 1000 person-years.
Older age, obesity and technical or higher education were statistically
associated with the incidence of diabetes.
CONCLUSION: Our results confirm that the incidence of diabetes in Peru is among
the highest reported globally. The fast economic growth in the last 20 years,
high overweight and obesity rates may have triggered this phenomenon.
DOI: 10.1136/bmjdrc-2017-000401
PMCID: PMC5574423
PMID: 28878935
Conflict of interest statement: Competing interests: SNS has received honoraria
from Sanofi for participation in this study. He also provided ad hoc consultancy
to Novo Nordisk. CM is a employee of Sanofi Perú
116. Med Sci Monit. 2018 Feb 28;24:1232-1240.
Elevated Levels of Serum β2-Glycoprotein I/Oxidized Low-Density Lipoprotein
Complexes Are Associated with Cerebral Infarction in Patients with Type 2
Diabetes Mellitus.
Zhang L(1), Wu Y(1), Qiu L(1), Liu Y(2), Li Q(1).
Author information:
(1)Department of Endocrinology, Second Affiliated Hospital of Harbin Medical
University Heilongjiang, Harbin, Heilongjiang, China (mainland).
(2)Department of Clinical Laboratory Medicine, Second Affiliated Hospital of
Harbin Medical University Heilongjiang, Harbin, Heilongjiang, China (mainland).
BACKGROUND To determine whether the levels of b2-glycoprotein I (b2-GPI)/oxidized
low-density lipoprotein (oxLDL) complexes are correlated with cerebral infarction
in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The levels
of β2-GPI/oxLDL complexes, oxLDL, routine lipid/lipoprotein parameters, oxidative
stress molecules, and inflammatory factors were measured in 78 healthy controls,
82 diabetics without cerebral infarction, and 79 diabetics with cerebral

infarction. Correlation, multiple linear regression, and logistic regression
analyses were performed. RESULTS Serum β2-GPI/oxLDL complexes and oxLDL levels
were significantly elevated in cerebral infarction in patients with T2DM
(β2-GPI/oxLDL: 1.09±0.16 U/mL; oxLDL: 47.83±8.17 mmol/L) compared with T2DM
without cerebral infarction (b2-GPI/oxLDL: 0.95±0.13 U/mL; oxLDL: 41.24±7.12
mmol/L) and healthy controls (β2-GPI/oxLDL: 0.81±0.12 U/mL; oxLDL: 27.97±4.57
mmol/L). The levels of β2-GPI/oxLDL complex in lacunar infarction (1.16±0.15
U/ml) were significantly higher than atherothrombotic infarction (1.07±0.19 U/ml)
and cardioembolic infarction (1.00±0.23 U/ml). In all patients with T2DM, the
β2-GPI/oxLDL levels were positively correlated with total cholesterol (r=0.474,
p=0.001) and triglycerides (r=0.431, p=0.003). oxLDL levels were positively
correlated with total cholesterol (r=0.445, p=0.002). The logistic regression
analysis indicated that elevated b2-GPI/oxLDL and oxLDL levels were independently
associated with diabetic cerebral infarction. CONCLUSIONS Elevated levels of
serum b2-GPI/oxLDL complexes are associated with cerebral infarction in patients
with T2DM, especially in those with lacunar infarction.
PMCID: PMC5841189
117. J Diabetes Sci Technol. 2017 Sep;11(5):904-913. doi: 10.1177/1932296817702169.
Epub 2017 Mar 28.
Endovascular Devices and Revascularization Techniques for Limb-Threatening
Ischemia in Individuals With Diabetes.
Chung J(1).
Author information:
(1)1 Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey
Department of Surgery, Baylor College of Medicine, Houston TX, USA.
Diabetes mellitus (DM) is a rapidly worsening global epidemic over the last
thirty-five years. The increased prevalence of DM has changed the phenotypic
expression of atherosclerotic limb threatening ischemia (LTI), resulting in an
increase in lesions in the tibial vessels. These patients are also afflicted with
peripheral neuropathy, foot deformities, and medial calcification of the
vasculature. In response to the evolving phenotype of atherosclerosis, newer
minimally invasive tools and techniques have been developed to improve the blood
supply in LTI. Arterial access, traditionally obtained from the contralateral
common femoral artery (CFA) in a retrograde fashion, is now also frequently being
obtained in the ipsilateral limb in an antegrade fashion. Retrograde access of
the tibial, pedal, tarsal, or calf collateral vessels is also being utilized to
provide a route through which wires, catheters, balloons and stents may be
placed. Wires have evolved to have a variety of diameters, materials and coatings
providing interventionalists with a wide variety of choices when attempting to
traverse blockages in the arteries. When catheters and wires fail to traverse the
lesion, newer chronic total occlusion (CTO) devices have been developed to aid in
the placement of a wire across the offending lesions. Due to medial calcification
associated with DM, atherectomy devices have been developed to debulk the
atherosclerotic plaque within the vessel. High pressure balloon angioplasty with
or without stents remain the mainstay of intervention, with drug-coated balloons
(DCBs) and drug-eluting stents (DESs) now being frequently used to prevent
reocclusions of atherosclerotic lesions.
DOI: 10.1177/1932296817702169
PMCID: PMC5950991

118. BMC Med. 2017 Jul 19;15(1):131. doi: 10.1186/s12916-017-0901-x.
Environmental/lifestyle factors in the pathogenesis and prevention of type 2
diabetes.
Kolb H(1)(2), Martin S(3)(4).
Author information:
(1)Faculty of Medicine, University of Duesseldorf, Duesseldorf, Germany.
hubert.kolb@uni-duesseldorf.de.
(2)West-German Centre of Diabetes and Health, Duesseldorf Catholic Hospital
Group, Hohensandweg 37, 40591, Duesseldorf, Germany.
hubert.kolb@uni-duesseldorf.de.
(3)Faculty of Medicine, University of Duesseldorf, Duesseldorf, Germany.
(4)West-German Centre of Diabetes and Health, Duesseldorf Catholic Hospital
Group, Hohensandweg 37, 40591, Duesseldorf, Germany.
BACKGROUND: Environmental and lifestyle changes, in addition to the ageing of
populations, are generally believed to account for the rapid global increase in
type 2 diabetes prevalence and incidence in recent decades.
DISCUSSION: In this review, we present a comprehensive overview of factors
contributing to diabetes risk, including aspects of diet quality and quantity,
little physical activity, increased monitor viewing time or sitting in general,
exposure to noise or fine dust, short or disturbed sleep, smoking, stress and
depression, and a low socioeconomic status. In general, these factors promote an
increase in body mass index. Since loss of β-cell function is the ultimate cause
of developing overt type 2 diabetes, environmental and lifestyle changes must
have resulted in a higher risk of β-cell damage in those at genetic risk.
Multiple mechanistic pathways may come into play.
CONCLUSIONS: Strategies of diabetes prevention should aim at promoting a
'diabetes-protective lifestyle' whilst simultaneously enhancing the resistance of

the human organism to pro-diabetic environmental and lifestyle factors. More
research on diabetes-protective mechanisms seems warranted.
DOI: 10.1186/s12916-017-0901-x
PMCID: PMC5516328
119. Nanomaterials (Basel). 2017 Feb 15;7(2). pii: E39. doi: 10.3390/nano7020039.
An Enzymatic Glucose Sensor Composed of Carbon-Coated Nano Tin Sulfide.
Chung RJ(1), Wang AN(2), Peng SY(3).
Author information:
(1)Department of Chemical Engineering and Biotechnology, National Taipei
University of Technology (Taipei Tech), Taipei 10608, Taiwan.
rjchung@ntut.edu.tw.
dai20020223@gmail.com.
terrypntut@gmail.com.
In this study, a biosensor, based on a glucose oxidase (GOx) immobilized,
carbon-coated tin sulfide (SnS) assembled on a glass carbon electrode (GCE) was
developed, and its direct electrochemistry was investigated. The carbon coated
SnS (C-SnS) nanoparticle was prepared through a simple two-step process, using
hydrothermal and chemical vapor deposition methods. The large reactive surface
area and unique electrical potential of C-SnS could offer a favorable

microenvironment for facilitating electron transfer between enzymes and the
electrode surface. The structure and sensor ability of the proposed GOx/C-SnS
electrode were characterized using scanning electron microscopy (SEM), X-ray
diffraction (XRD), Raman spectroscopy, UV-vis spectroscopy, Fourier transform
infrared spectroscopy (FTIR), and cyclic voltammetry study (CV).
DOI: 10.3390/nano7020039
PMCID: PMC5333024
PMID: 28336872
120. J Cell Mol Med. 2018 Mar;22(3):1720-1732. doi: 10.1111/jcmm.13453. Epub 2018 Jan
4.
European versus Asian differences for the associations between paraoxonase-1
genetic polymorphisms and susceptibility to type 2 diabetes mellitus.
Luo JQ(1)(2), Ren H(3)(4), Liu MZ(1)(2), Fang PF(1)(2), Xiang DX(1)(2).
Author information:
(1)Department of Pharmacy, The Second Xiangya Hospital, Central South University,
Changsha, Hunan, China.
(2)Institute of Clinical Pharmacy, Central South University, Changsha, Hunan,
China.
(3)Department of Clinical Pharmacology, Xiangya Hospital, Central South
University, Changsha, China.
(4)Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,
Central South University, Changsha, China.
Many studies have examined the associations between paraoxonase-1 (PON1) genetic
polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2
diabetes mellitus (T2DM) across different ethnic populations. However, the
evidence for the associations remains inconclusive. In this study, we performed a
meta-analysis to clarify the association of the two PON1 variants with T2DM risk.
We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases
for studies published before June 2017. The pooled odds ratios (ORs) for the
association and their corresponding 95% confidence intervals (CIs) were
calculated by a random- or fixed-effect model. A total of 50 eligible studies,
including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M
(rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the
192R allele was a susceptible factor of T2DM in the South or East Asian
population (OR > 1, P < 0.05) but represented a protective factor of T2DM in
European population (OR = 0.66, 95% CI = 0.45-0.98) under a heterozygous genetic
model. With regard to the PON1 L55M polymorphism, significant protective effects
of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61-0.97)
and dominant (OR = 0.80, 95% CI = 0.65-0.99) genetic models were found in the
European population, while no significant associations in the Asian populations
under all genetic models (P > 0.05). In summary, by a comprehensive
meta-analysis, our results firmly indicated that distinct effects of PON1 genetic
polymorphisms existed in the risk of T2DM across different ethnic backgrounds.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John
Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
DOI: 10.1111/jcmm.13453
PMCID: PMC5824408
PMID: 29314660
121. BMJ Open Diabetes Res Care. 2016 Aug 18;4(1):e000275. doi:

Evaluation of statin prescriptions in type 2 diabetes: India Heart Watch-2.
Gupta R(1), Lodha S(1), Sharma KK(2), Sharma SK(3), Gupta S(4), Asirvatham AJ(5),
Mahanta BN(6), Maheshwari A(7), Sharma DC(8), Meenawat AS(9), Khedar RS(1).
Author information:
(1)Departments of Preventive Cardiology, Internal Medicine and Endocrinology ,
Eternal Heart Care Centre and Research Institute, Mount Sinai New York Affiliate
, Jaipur, Rajasthan , India.
(2)Research Unit, Fortis Escorts Hospital , Jaipur, Rajasthan , India.
(3)Department of Endocrinology , Galaxy Specialty Centre , Jaipur, Rajasthan,
India.
(4)Department of Diabetes , Diabetes Care and Research Centre , Nagpur,
Maharashtra , India.
(5)Department of Diabetes , Madurai Medical College , Madurai, Tamil Nadu ,
India.
(6)Department of Medicine , Assam Medical College , Dibrugarh, Assam , India.
(7)Department of Medicine , BBD College of Dental Sciences , Lucknow, Uttar
Pradesh , India.
(8)Department of Endocrinology , RNT Medical College , Udaipur, Rajasthan ,
India.
(9)Department of Medicine , Satyam Hospital , Jodhpur, Rajasthan , India.
BACKGROUND: Contemporary treatment guidelines advise statin use in all patients
with diabetes for reducing coronary risk. Use of statins in patients with type 2
diabetes has not been reported from India.
METHODS: We performed a multisite (n=9) registry-based study among internists
(n=3), diabetologists (n=3), and endocrinologists (n=3) across India to determine
prescriptions of statins in patients with type 2 diabetes. Demographic and
clinical details were obtained and prescriptions were audited for various
medications with a focus on statins. Details of type of statin and dosage form
(low, moderate, and high) were obtained. Patients were divided into categories
based on presence of cardiovascular risk into low (no risk factors, n=1506),
medium (≥1 risk factor, n=5425), and high (with vascular disease, n=1769).
Descriptive statistics are presented.
RESULTS: Prescription details were available in 8699 (men 5292, women 3407).
Statins were prescribed in 55.2% and fibrates in 9.2%. Statin prescription was
significantly greater among diabetologists (64.4%) compared with internists
(n=53.3%) and endocrinologists (46.8%; p<0.001). Atorvastatin was prescribed in
74.1%, rosuvastatin in 29.2%, and others in 3.0%. Statin prescriptions were lower
in women (52.1%) versus men (57.2%; p<0.001) and in patients aged <40 years
(34.3%), versus those aged 40-49 (49.7%), 50-59 (60.1%), and ≥60 years (62.2%;
p<0.001). Low-dose statins were prescribed in 1.9%, moderate dose in 85.4%, and
high dose in 12.7%. Statin prescriptions were greater in the high-risk group
(58.0%) compared with those in the medium-risk (53.8%) and low-risk (56.8%)
groups (p <0.001). High-dose statin prescriptions were similar in the high-risk
(14.5%), medium-risk (11.8%), and low-risk (13.5%) groups (p=0.31).
CONCLUSIONS: Statins are prescribed in only half of the clinic-based patients in
India with type 2 diabetes. Prescription of high-dose statins is very low.
DOI: 10.1136/bmjdrc-2016-000275
PMCID: PMC5013346
PMID: 27648292
122. Popul Health Metr. 2017 May 12;15(1):18. doi: 10.1186/s12963-017-0136-2.
Evolution of the "fourth stage" of epidemiologic transition in people aged
80 years and over: population-based cohort study using electronic health records.
Hazra NC(1), Gulliford M(2)(3).

Author information:
(1)Department of Primary Care and Public Health Sciences, King's College London,
3rd Floor Addison House, Guy's Campus, London, SE1 1UL, UK.
nisha.hazra@kcl.ac.uk.
3rd Floor Addison House, Guy's Campus, London, SE1 1UL, UK.
(3)NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust,
Great Maze Pond, London, SE1 9RT, UK.
Erratum in
Popul Health Metr. 2017 Aug 4;15(1):30.
BACKGROUND: In the "fourth stage" of epidemiological transition, the distribution
of non-communicable diseases is expected to shift to more advanced ages, but
age-specific changes beyond 80 years of age have not been reported.
METHODS: This study aimed to evaluate demographic and health transitions in a
population aged 80 years and over in the United Kingdom from 1990 to 2014, using
primary care electronic health records. Epidemiological analysis of chronic
morbidities and age-related impairments included a cohort of 299,495
participants, with stratified sampling by five-year age group up to 100 years and
over. Cause-specific proportional hazards models were used to estimate hazard
ratios for incidence rates over time.
RESULTS: Between 1990 and 2014, nonagenarians and centenarians increased as a
proportion of the over-80 population, as did the male-to-female ratio among
individuals aged 80 to 95 years. A lower risk of coronary heart disease (HR 0.54,
95% confidence interval [CI]: 0.50-0.58), stroke (0.83, 0.76-0.90) and chronic
obstructive pulmonary disease (0.59, 0.54-0.64) was observed among 80-84
year-olds in 2010-2014 compared to 1995-1999. By contrast, the risk of type II
diabetes (2.18, 1.96-2.42), cancer (1.52, 1.43-1.61), dementia (2.94, 2.70-3.21),
cognitive impairment (5.57, 5.01-6.20), and musculoskeletal pain (1.26,
1.21-1.32) was greater in 2010-2014 compared to 1995-1999.

CONCLUSIONS: Redistribution of the over-80 population to older ages, and
declining age-specific incidence of cardiovascular and respiratory diseases in
over-80s, are consistent with the "fourth stage" of epidemiologic transition, but
increases in diabetes, cancer, and age-related impairment show new emerging
epidemiological patterns in the senior elderly.
DOI: 10.1186/s12963-017-0136-2
PMCID: PMC5429583
123. Diabetologia. 2018 Nov;61(11):2300-2309. doi: 10.1007/s00125-018-4700-5. Epub
2018 Aug 9.
Excess risk of hospitalisation for heart failure among people with type 2
diabetes.
Rosengren A(1)(2), Edqvist J(3)(4), Rawshani A(3), Sattar N(5), Franzén S(6),
Adiels M(7), Svensson AM(6), Lind M(3)(8), Gudbjörnsdottir S(3)(6).
Author information:
(1)Department of Molecular and Clinical Medicine, Institute of Medicine,
University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg,
Sweden. Annika.Rosengren@gu.se.
(2)Sahlgrenska University Hospital, Östra Hospital, Gothenburg, Sweden.
Annika.Rosengren@gu.se.
(3)Department of Molecular and Clinical Medicine, Institute of Medicine,
University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg,
Sweden.
(4)Sahlgrenska University Hospital, Östra Hospital, Gothenburg, Sweden.
(5)Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular

Research Centre, University of Glasgow, Glasgow, UK.
(6)Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden.
(7)Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden.
(8)Department of Medicine, NU Hospital Group, Uddevalla, Sweden.
AIMS/HYPOTHESIS: Type 2 diabetes is an established risk factor for heart failure,
but age-specific data are sparse. We aimed to determine excess risk of heart
failure, based on age, glycaemic control and kidney function in comparison with
age- and sex-matched control individuals from the general population.
METHODS: Individuals with type 2 diabetes registered in the Swedish National
Diabetes Registry 1998-2012 (n = 266,305) were compared with age-, sex- and
county-matched control individuals without diabetes (n = 1,323,504), and followed
over a median of 5.6 years until 31 December 2013.
RESULTS: We identified 266,305 individuals with type 2 diabetes (mean age
62.0 years, 45.3% women) and 1,323,504 control individuals. Of the individuals
with type 2 diabetes and control individuals, 18,715 (7.0%) and 50,157 (3.8%)
were hospitalised with a diagnosis of heart failure, respectively. Comparing
individuals with diabetes with those in the control group, men and women with
type 2 diabetes who were younger than 55 years of age had HRs for hospitalisation
for heart failure of 2.07 (95% CI 1.73, 2.48) and 4.59 (95% CI 3.50, 6.02),
respectively, using analyses adjusted for socioeconomic variables and associated
conditions. Younger age, poorer glycaemic control and deteriorating renal
function were all associated with increased excess risk of heart failure in those
with type 2 diabetes compared with the control group. However, people with
diabetes who were ≥75 years and without albuminuria or with good glycaemic
control (HbA1c ≤52 mmol/mol [≤6.9%]) had a similar risk of hospitalisation for
heart failure as control individuals in the same age group.
CONCLUSIONS/INTERPRETATION: Men and women aged <55 years with type 2 diabetes are
at markedly elevated excess risk of heart failure. The excess risk declined with
age, but persisted even with good glycaemic control. However, among those who
were 75 years and older, diabetic individuals with well controlled glucose levels
or without albuminuria had a risk of heart failure that was on a par with
individuals without diabetes.
DOI: 10.1007/s00125-018-4700-5
PMCID: PMC6182656
PMID: 30094466
124. Oxid Med Cell Longev. 2017;2017:9410954. doi: 10.1155/2017/9410954. Epub 2017 Jan
12.
Exercise Training Attenuates the Dysregulated Expression of Adipokines and
Oxidative Stress in White Adipose Tissue.
Sakurai T(1), Ogasawara J(1), Shirato K(1), Izawa T(2), Oh-Ishi S(3), Ishibashi
Y(1), Radák Z(4), Ohno H(5), Kizaki T(1).
Author information:
(1)Department of Molecular Predictive Medicine and Sport Science, Kyorin
University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
(2)Department of Sports Biochemistry, Faculty of Health and Sport Science,
Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto, Japan.
(3)National Hospital Organization Ibarakihigashi National Hospital, The Center of
Chest Diseases and Severe Motor and Intellectual Disabilities, Terunuma 825,
Tokai-mura, Naka-gun, Ibaraki, Japan.
(4)Institute of Sport Science, University of Physical Education, Alkotas u. 44,
TF, Budapest, Hungary.
(5)Social Medical Corporation, The Yamatokai Foundation, Nangai, Higashiyamato,
Tokyo, Japan.
Obesity-induced inflammatory changes in white adipose tissue (WAT), which caused
dysregulated expression of inflammation-related adipokines involving tumor
necrosis factor-α and monocyte chemoattractant protein-1, contribute to the
development of insulin resistance. Moreover, current literature reports state
that WAT generates reactive oxygen species (ROS), and the enhanced production of
ROS in obese WAT has been closely associated with the dysregulated expression of
adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress
that results from obesity is thought to be one of the important strategies in
preventing and improving lifestyle-related diseases. Exercise training (TR) not
only brings about a decrease in WAT mass but also attenuates obesity-induced
dysregulated expression of the adipokines in WAT. Furthermore, some reports
indicate that TR affects the generation of oxidative stress in WAT. This review
outlines the impact of TR on the expression of inflammation-related adipokines
and oxidative stress in WAT.
DOI: 10.1155/2017/9410954
PMCID: PMC5266865
Conflict of interest statement: The authors declare that there is no conflict of
interests regarding the publication of this paper.
eCollection 2017.
EZSCAN for undiagnosed type 2 diabetes mellitus: A systematic review and
meta-analysis.
Bernabe-Ortiz A(1)(2)(3), Ruiz-Alejos A(1), Miranda JJ(1)(4), Mathur R(2), Perel
P(2), Smeeth L(2).

Author information:
Tropical Medicine, London, United Kingdom.
(3)Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas-UPC, Lima,
Perú.
(4)Department of Medicine, School of Medicine, Universidad Peruana Cayetano
OBJECTIVES: The EZSCAN is a non-invasive device that, by evaluating sweat gland
function, may detect subjects with type 2 diabetes mellitus (T2DM). The aim of
the study was to conduct a systematic review and meta-analysis including studies
assessing the performance of the EZSCAN for detecting cases of undiagnosed T2DM.
METHODOLOGY/PRINCIPAL FINDINGS: We searched for observational studies including
diagnostic accuracy and performance results assessing EZSCAN for detecting cases
of undiagnosed T2DM. OVID (Medline, Embase, Global Health), CINAHL and SCOPUS
databases, plus secondary resources, were searched until March 29, 2017. The
following keywords were utilized for the systematic searching: type 2 diabetes
mellitus, hyperglycemia, EZSCAN, SUDOSCAN, and sudomotor function. Two
investigators extracted the information for meta-analysis and assessed the
quality of the data using the Revised Version of the Quality Assessment of
Diagnostic Accuracy Studies (QUADAS-2) checklist. Pooled estimates were obtained
by fitting the logistic-normal random-effects model without covariates but random
intercepts and using the Freeman-Tukey Arcsine Transformation to stabilize
variances. Heterogeneity was also assessed using the I2 measure. Four studies (n
= 7,720) were included, three of them used oral glucose tolerance test as the
gold standard. Using Hierarchical Summary Receiver Operating Characteristic
model, summary sensitivity was 72.0% (95%CI: 60.0%- 83.0%), whereas specificity
was 56.0% (95%CI: 38.0%- 74.0%). Studies were very heterogeneous (I2 for
sensitivity: 79.2% and for specificity: 99.1%) regarding the inclusion criteria
and bias was present mainly due to participants selection.
CONCLUSIONS: The sensitivity of EZSCAN for detecting cases of undiagnosed T2DM
seems to be acceptable, but evidence of high heterogeneity and participant
selection bias was detected in most of the studies included. More studies are
needed to evaluate the performance of the EZSCAN for undiagnosed T2DM screening,
especially at the population level.
PMCID: PMC5662214
eCollection 2017.
Factors associated with pre-diabetes in Tehranian men and women: A structural
equations modeling.
Amiri P(1), Jalali-Farahani S(1)(2), Karimi M(3)(1), Taherian R(1)(2),
Kazempour-Ardebili S(4), Hosseini-Esfahani F(5), Mirmiran P(5), Azizi F(4).
Author information:
(1)Research Center for Social Determinants of Health, Research Institute for
(2)Student Research Committee, Shahid Beheshti University of Medical Sciences,
Tehran, Iran.

(5)Nutrition and Endocrine Research Center, Research Institute for Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
OBJECTIVE: To examine associations of sex-specific related factors with
pre-diabetes in Tehranian non-diabetic adults.
METHODS: This study has been conducted within the framework of the Tehran Lipid
and Glucose Study (TLGS) between 2008-2010. A total of 5568 (55.4% female)
non-diabetic adults, aged ≥20 years, selected from among participants of the
TLGS, were recruited for the study. Data on socio-behavioral factors, family
history of diabetes and cardio-metabolic risk factors were included in the
hypothesized model to test their direct and indirect associations with
pre-diabetes in men and women separately, using structural equation modeling.
RESULTS: Pre-diabetes was diagnosed in 23.6% of participants, with significantly
higher prevalence in men compared to women (27.4% and 20.5%, respectively;
p<0.001). Body mass index (BMI) and triglycerides (TG) in both sexes and
hypertension and high density lipoprotein only in women, were directly associated
with pre-diabetes (p<0.05). Poor diet in women was the only behavioral factor
directly associated with pre-diabetes (p<0.05). Age in both sexes and education,
only in women, were directly associated with pre-diabetes. In both genders, age,
marital status, education, employment, poor diet and leisure time physical
activity were indirectly associated with pre-diabetes through cardio-metabolic
risk factors.
CONCLUSIONS: The main modifiable factors directly associated with pre-diabetes
were TG in women and BMI in men, which need to be prioritized in health policies
for diabetes prevention programs in Tehranian adults. Future research should
focus on the gender-specific determinants and underlying mechanisms for TG levels
and BMI status among this population.
PMCID: PMC5720750

127. BMC Health Serv Res. 2018 Sep 24;18(1):732. doi: 10.1186/s12913-018-3448-4.
Factors associated with self-care practice among adult diabetes patients in West
Shoa Zone, Oromia Regional State, Ethiopia.
Gurmu Y(1), Gela D(2), Aga F(3).
Author information:
(1)Department of Nursing, College of Medicine & Health Sciences, Ambo University,
P. O. Box: 19, Ambo, Ethiopia.
(2)Department of Nursing & Midwifery, School of Allied Health Sciences, College
of Health Science, Addis Ababa University, P.O. Box: 4412, Addis Ababa, Ethiopia.
debegela@gmail.com.
(3)Department of Nursing & Midwifery, School of Allied Health Sciences, College
of Health Science, Addis Ababa University, P.O. Box: 9083, Addis Ababa, Ethiopia.
BACKGROUND: Diabetes, a rising global health problem, requires continuous
self-care practice to prevent acute and chronic complications. However, studies
show that few diabetes patients practice the recommended self-care in Ethiopia.
The aim of this study was to assess factors associated with self-care practice
among adult diabetes patients in public hospitals of West Shoa Zone, Oromia
Regional State, Ethiopia.
METHODS: In this cross-sectional study, 257 diabetes patients (mean age
42.9 ± 14.6 years, 54.1% male) completed the survey in Afan Oromo and Amharic
languages. A questionnaire consisting standardized tools was used to collect the
data. Descriptive and logistic regression analyses were conducted using SPSS
version 21.
RESULTS: The mean score for diabetes self-care was 39.8 ± 9.5 and 45.5% of the
participants scored below the mean. Multiple logistic regression analysis

revealed that having higher diabetes knowledge (AOR = 2.42, 95% CI = 1.22, 4.80),
self-efficacy (AOR = 3.30, 95% CI = 1.64, 6.62), social support (AOR = 2.86, 95%
CI = 1.37, 5.96), secondary school education (AOR = 6.0, 95% CI = 1.90, 18.85),
and longer duration of diabetes (AOR = 5.55, 95% CI = 2.29, 13.44) were important
predictors of good diabetes self-care practice.
CONCLUSION: The diabetes education programs should use strategies that enhance
patients' diabetes knowledge, self-efficacy, and social support. Patients with
recent diabetes diagnosis need special attention as they may relatively lack
knowledge and skills in self-care. Further studies are needed to elucidate
pathways through which diabetes knowledge, self-efficacy, social support, and
health literacy affect diabetes self-care.
DOI: 10.1186/s12913-018-3448-4
PMCID: PMC6154910
PMID: 30249246
128. Nutrients. 2018 Sep 1;10(9). pii: E1193. doi: 10.3390/nu10091193.
Fatty Acid Profiles of Various Vegetable Oils and the Association between the Use
of Palm Oil vs. Peanut Oil and Risk Factors for Non-Communicable Diseases in
Yangon Region, Myanmar.
Aung WP(1)(2), Bjertness E(3), Htet AS(4)(5), Stigum H(6), Chongsuvivatwong V(7),
Soe PP(8), Kjøllesdal MKR(9).
Author information:
(1)Department of Community Medicine and Global Health, Institute of Health and
Society, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway.
waiphyoaung77@gmail.com.
(2)Procurement and Supply Division, Department of Public Health, Ministry of

Health and Sports, Nay Pyi Taw 15011, Myanmar. waiphyoaung77@gmail.com.
espen.bjertness@medisin.uio.no.
aungsh@gmail.com.
(5)International Relations Division, Ministry of Health and Sports, Nay Pyi Taw
15011, Myanmar. aungsh@gmail.com.
hein.stigum@medisin.uio.no.
(7)Epidemiology Unit, Prince of Songkla University, Hat Yai 90110, Thailand.
cvirasak@gmail.com.
(8)Department of Preventive and Social Medicine, University of Medicine 1, Yangon
11131, Myanmar. papasoe.jpn@gmail.com.
m.k.kjollesdal@medisin.uio.no.
The majority of vegetable oils used in food preparation in Myanmar are imported
and sold non-branded. Little is known about their fatty acid (FA) content. We
aimed to investigate the FA composition of commonly used vegetable oils in the
Yangon region, and the association between the use of palm oil vs. peanut oil and
risk factors for non-communicable disease (NCD). A multistage cluster survey was
conducted in 2016, and 128 oil samples from 114 households were collected. Data
on NCD risk factors were obtained from a household-based survey in the same
region, between 2013 and 2014. The oils most commonly sampled were non-branded
peanut oil (43%) and non-branded palm oil (19%). Non-branded palm oil had a
significantly higher content of saturated fatty acids (36.1 g/100 g) and a lower
content of polyunsaturated fatty acids (9.3 g/100 g) than branded palm oil. No
significant differences were observed regarding peanut oil. Among men, palm oil
users had significantly lower mean fasting plasma glucose levels and mean BMI
than peanut oil users. Among women, palm oil users had significantly higher mean
diastolic blood pressure, and higher mean levels of total cholesterol and
triglycerides, than peanut oil users. Regulation of the marketing of non-branded
oils should be encouraged.
DOI: 10.3390/nu10091193
PMCID: PMC6163161
PMID: 30200403
129. Nat Rev Endocrinol. 2017 Oct;13(10):599-609. doi: 10.1038/nrendo.2017.78. Epub
2017 Jun 30.
FGF1 - a new weapon to control type 2 diabetes mellitus.
Gasser E(1), Moutos CP(1)(2)(3), Downes M(1), Evans RM(1)(2).
Author information:
(1)Gene Expression Laboratory, Salk Institute for Biological Studies.
(2)Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010
North Torrey Pines Road, La Jolla, California 92037, USA.
(3)College of Medicine, University of Arkansas for Medical Sciences, 4301 West
Markham Street, Little Rock, Arkansas 72205, USA.
A hypercaloric diet combined with a sedentary lifestyle is a major risk factor
for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and
associated comorbidities. Standard treatment for T2DM begins with lifestyle
modification, and includes oral medications and insulin therapy to compensate for
progressive β-cell failure. However, current pharmaceutical options for T2DM are
limited in that they do not maintain stable, durable glucose control without the
need for treatment intensification. Furthermore, each medication is associated
with adverse effects, which range from hypoglycaemia to weight gain or bone loss.
Unexpectedly, fibroblast growth factor 1 (FGF1) and its low mitogenic variants
have emerged as potentially safe candidates for restoring euglycaemia, without
causing overt adverse effects. In particular, a single peripheral injection of
FGF1 can lower glucose to normal levels within hours, without the risk of
hypoglycaemia. Similarly, a single intracerebroventricular injection of FGF1 can
induce long-lasting remission of the diabetic phenotype. This Review discusses
potential mechanisms by which centrally administered FGF1 improves central
glucose-sensing and peripheral glucose uptake in a sustained manner.
Specifically, we explore the potential crosstalk between FGF1 and glucose-sensing
neuronal circuits, hypothalamic neural stem cells and synaptic plasticity.
Finally, we highlight therapeutic considerations of FGF1 and compare its
metabolic actions with FGF15 (rodents), FGF19 (humans) and FGF21.
DOI: 10.1038/nrendo.2017.78
PMCID: PMC5839646
130. BMC Complement Altern Med. 2018 Oct 19;18(1):282. doi: 10.1186/s12906-018-2346-y.
Free radical scavenging, α-glucosidase inhibitory and lipase inhibitory
activities of eighteen Sudanese medicinal plants.
Elbashir SMI(1), Devkota HP(2)(3), Wada M(4), Kishimoto N(5), Moriuchi M(6),
Shuto T(6), Misumi S(5), Kai H(6), Watanabe T(1)(4).
Author information:
(1)Department of Medicinal Botany, Graduate School of Pharmaceutical Sciences,

Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto, 862-0973,
Japan.
(2)Department of Medicinal Botany, Graduate School of Pharmaceutical Sciences,
Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto, 862-0973,
Japan. devkotah@kumamoto-u.ac.jp.
(3)Program for Leading Graduate Schools, Health Life Science: Interdisciplinary
and Glocal Oriented (HIGO) Program, Kumamoto University, Kumamoto, Japan.
devkotah@kumamoto-u.ac.jp.
(4)School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto,
Kumamoto, 862-0973, Japan.
(5)Department of Environmental and Molecular Health Sciences, Faculty of Medical
and Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan.
(6)Department of Molecular Medicine, Faculty of Medical and Pharmaceutical
Sciences, Kumamoto University, Kumamoto, 862-0973, Japan.
BACKGROUND: Lifestyle-related diseases such as diabetes are steadily increasing
worldwide. In Sudan, there are a variety of plant species used traditionally for
the treatment of diabetes, obesity and other symptoms which need to be validated
through scientific studies for their claimed traditional uses. Therefore, in the
current study, the free radical scavenging activity, α-glucosidase inhibitory and
pancreatic lipase inhibitory activities of 70% ethanol and water extracts of
eighteen Sudanese medicinal plants were investigated using various in vitro
assays. Moreover, the cytotoxicity and genotoxicity were assessed for the
bioactive plant extracts.
METHODS: Eighteen plants were selected on the basis of their traditional uses and
extracted with 70% ethanol and water to obtain thirty-six extracts. The obtained
extracts were screened using different in vitro bioassays namely,
1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, α-glucosidase inhibitory
and pancreatic lipase inhibitory assays. Furthermore, the active plant extracts
were investigated for their cytotoxicity and genotoxicity on HeLa cell line using
HCS DNA Damage Assay.

RESULTS: Both 70% ethanol and water extracts of Acacia nilotica, Ziziphus
spina-christi, Abrus precatorius, and Geigeria alata along with the 70% ethanol
extract of Martynia annua showed potent free radical scavenging activity.
Regarding the α-glucosidase inhibition assay, both extracts of Acacia nilotica,
Ziziphus spina-christi, Geigeria alata, and Cyperus rotundus showed potent
activity. In general, 70% ethanol extracts were more potent compared to water
extracts with exception of Cordia sinensis and Cymbopogon proximus, for which
water extracts also showed potent enzyme inhibitory activity. Similarly, water
extracts of Acacia nilotica and Ziziphus spina-christi showed potent inhibitory
activity against pancreatic lipase enzyme. Some of the extracts also showed
significant genotoxicity and cytotoxicity at the concentration range used for
bioactivities.
CONCLUSION: The extracts of Acacia nilotica, Ziziphus spina-christi, Geigeria
alata, Martynia annua and Abrus precatorius exhibited an appreciable range of
activity on antioxidant and enzyme inhibitory assays.
DOI: 10.1186/s12906-018-2346-y
PMCID: PMC6194694
PMID: 30340582
131. BMC Geriatr. 2018 Mar 15;18(1):73. doi: 10.1186/s12877-018-0762-y.
Frequent pain in older people with and without diabetes - Finnish community based
study.
Karjalainen M(1)(2), Saltevo J(3), Tiihonen M(4), Haanpää M(5)(6), Kautiainen
H(7)(8), Mäntyselkä P(1)(8).
Author information:
(1)Institute of Public Health and Clinical Nutrition, General Practice,

University of Eastern Finland, Kuopio, Finland.
(2)Inner Savo Health Center, Suonenjoki, Finland.
(3)Central Finland Central Hospital, Jyväskylä, Finland.
(4)School of Pharmacy, University of Eastern Finland, P.O. BOX 1627, FI-70211,
Kuopio, Finland. miia.tiihonen@uef.fi.
(5)Etera Mutual Pension Insurance Company, Vantaa, Finland.
(6)Department of Neurosurgery, Helsinki University Hospital, Helsinki, Finland.
(7)Unit of Primary Health Care, Helsinki University Central Hospital, Helsinki,
Finland.
(8)Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland.
BACKGROUND: The association between pain and diabetes in older people has been
largely unexplored. The aim of this survey was to analyze the prevalence and
characteristics of pain among Finnish men and women 65 or older with and without
diabetes in primary care.
METHODS: All home-dwelling persons 65 years or older with diabetes (N = 527) and
age and gender matched controls (N = 890) were identified from electronic patient
records. Frequent pain was regarded as any pain experienced more often than once
a week, and it was divided into pain experienced several times a week but not
daily and pain experienced daily or continuously. The Numeric Rating Scale (0-10)
(NRS) was used to assess the intensity and interference of the pain.
RESULTS: The number of subjects who returned the questionnaire was 1084 (76.5%).
The prevalence of frequent pain in the preceding week was 50% among women without
diabetes and 63% among women with diabetes (adjusted, p = 0.22). In men, the
corresponding proportions were 42% without diabetes and 47% with diabetes
(adjusted, p = 0.58). In both genders, depressive symptoms and the number of
comorbidities were associated with pain experienced more often than once a week
and with daily pain. Diabetes was not associated with pain intensity or pain
interference in either women or men.
CONCLUSIONS: Pain in older adults is associated with depressive symptoms and the
number of comorbidities more than with diabetes itself.

DOI: 10.1186/s12877-018-0762-y
PMCID: PMC5856375
132. Eur Heart J. 2018 Jul 7;39(26):2497-2505. doi: 10.1093/eurheartj/ehx518.
Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery
disease.
Mirtschink P(1)(2), Jang C(3), Arany Z(3), Krek W(1).
Author information:
(1)Department of Biology, Institute of Molecular Health Sciences, ETH Zurich,
Otto-Stern-Weg 7, Zurich, Switzerland.
(2)Department of Clinical Pathobiochemistry, Institute of Clinical Chemistry and
Laboratory Medicine, University Hospital Dresden, Fetscherstr. 74, Dresden,
Germany.
(3)Department of Medicine, Cardiovascular Institute and Institute Diabetes
Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania,
11th floor, Civic Blvd, Philadelphia, 19104 PA, USA.
Despite strong indications that increased consumption of added sugars correlates
with greater risks of developing cardiometabolic syndrome (CMS) and
cardiovascular disease (CVD), independent of the caloric intake, the worldwide
sugar consumption remains high. In considering the negative health impact of
overconsumption of dietary sugars, increased attention is recently being given to
the role of the fructose component of high-sugar foods in driving CMS. The
primary organs capable of metabolizing fructose include liver, small intestine,
and kidneys. In these organs, fructose metabolism is initiated by ketohexokinase

(KHK) isoform C of the central fructose-metabolizing enzyme KHK. Emerging data
suggest that this tissue restriction of fructose metabolism can be rescinded in
oxygen-deprived environments. In this review, we highlight recent progress in
understanding how fructose metabolism contributes to the development of major
systemic pathologies that cooperatively promote CMS and CVD, reference recent
insights into microenvironmental control of fructose metabolism under stress
conditions and discuss how this understanding is shaping preventive actions and
therapeutic approaches.
DOI: 10.1093/eurheartj/ehx518
PMID: 29020416
133. Diabetes Care. 2018 May;41(5):1097-1105. doi: 10.2337/dc17-1795.
Gaps in Guidelines for the Management of Diabetes in Low- and Middle-Income
Versus High-Income Countries-A Systematic Review.
Owolabi MO(1), Yaria JO(2), Daivadanam M(3)(4), Makanjuola AI(2), Parker G(5),
Oldenburg B(6), Vedanthan R(7), Norris S(8), Oguntoye AR(2), Osundina MA(2),
Herasme O(7), Lakoh S(2), Ogunjimi LO(2), Abraham SE(2), Olowoyo P(9), Jenkins
C(10), Feng W(10), Bayona H(11), Mohan S(12), Joshi R(13), Webster R(13), Kengne
AP(14), Trofor A(15), Lotrean LM(16), Praveen D(17), Zafra-Tanaka JH(18),
Lazo-Porras M(18), Bobrow K(19), Riddell MA(20), Makrilakis K(21), Manios Y(22),
Ovbiagele B(10); COUNCIL Initiative.
Author information:
(1)University of Ibadan, Ibadan, Nigeria mayowaowolabi@yahoo.com.
(2)University College Hospital, Ibadan, Nigeria.
(3)Department of Food, Nutrition and Dietetics, Uppsala University, Uppsala,

Sweden.
(4)Department of Public Health Sciences, Karolinska Institutet, Solna, Sweden.
(5)University College London, London, U.K.
(6)The University of Melbourne, Melbourne, Australia.
(7)Icahn School of Medicine at Mount Sinai, New York, NY.
(8)University of the Witwatersrand, Johannesburg, South Africa.
(9)Federal Teaching Hospital, Ido-Ekiti, Nigeria.
(10)Medical University of South Carolina, Charleston, SC.
(11)Fundación Santa Fe de Bogotá Hospital, University of the Andes, Bogota,
Colombia.
(12)Public Health Foundation of India, New Delhi, India.
(13)The George Institute for Global Health, The University of New South Wales,
Sydney, Australia.
(14)South African Medical Research Council, Cape Town, South Africa.
(15)Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania.
(16)Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
(17)The George Institute for Global Health, New Delhi, India.
(18)Universidad Peruana Cayetano Heredia, Lima, Peru.
(19)University of Cape Town, Cape Town, South Africa.
(20)Monash University, Melbourne, Australia.
(21)National and Kapodistrian University of Athens, Athens, Greece.
(22)Harokopio University, Athens, Greece.
OBJECTIVE: The extent to which diabetes (DM) practice guidelines, often based on
evidence from high-income countries (HIC), can be implemented to improve outcomes
in low- and middle-income countries (LMIC) is a critical challenge. We carried
out a systematic review to compare type 2 DM guidelines in individual LMIC versus
HIC over the past decade to identify aspects that could be improved to facilitate
implementation.
RESEARCH DESIGN AND METHODS: Eligible guidelines were sought from online
databases and websites of diabetes associations and ministries of health. Type 2

DM guidelines published between 2006 and 2016 with accessible full publications
were included. Each of the 54 eligible guidelines was assessed for compliance
with the Institute of Medicine (IOM) standards, coverage of the cardiovascular
quadrangle (epidemiologic surveillance, prevention, acute care, and
rehabilitation), translatability, and its target audiences.
RESULTS: Most LMIC guidelines were inadequate in terms of applicability, clarity,
and dissemination plan as well as socioeconomic and ethical-legal
contextualization. LMIC guidelines targeted mainly health care providers, with
only a few including patients (7%), payers (11%), and policy makers (18%) as
their target audiences. Compared with HIC guidelines, the spectrum of DM clinical
care addressed by LMIC guidelines was narrow. Most guidelines from the LMIC
complied with less than half of the IOM standards, with 12% of the LMIC
guidelines satisfying at least four IOM criteria as opposed to 60% of the HIC
guidelines (P < 0.001).
CONCLUSIONS: A new approach to the contextualization, content development, and
delivery of LMIC guidelines is needed to improve outcomes.
DOI: 10.2337/dc17-1795
134. Front Genet. 2016 Sep 20;7:168. eCollection 2016.
Gender Differences in Adipocyte Metabolism and Liver Cancer Progression.
Cheung OK(1), Cheng AS(2).
Author information:
(1)School of Biomedical Sciences, The Chinese University of Hong Kong Hong Kong,
China.
(2)School of Biomedical Sciences, The Chinese University of Hong Kong Hong Kong,
China; State Key Laboratory of Digestive Disease, The Chinese University of Hong
Kong Hong Kong, China.
Liver cancer is the third most common cancer type and the second leading cause of
deaths in men. Large population studies have demonstrated remarkable gender
disparities in the incidence and the cumulative risk of liver cancer. A number of
emerging risk factors regarding metabolic alterations associated with obesity,
diabetes and dyslipidemia have been ascribed to the progression of non-alcoholic
fatty liver diseases (NAFLD) and ultimately liver cancer. The deregulation of fat
metabolism derived from excessive insulin, glucose, and lipid promotes
cancer-causing inflammatory signaling and oxidative stress, which eventually
triggers the uncontrolled hepatocellular proliferation. This review presents the
current standing on the gender differences in body fat compositions and their
mechanistic linkage with the development of NAFLD-related liver cancer, with an
emphasis on genetic, epigenetic and microRNA control. The potential roles of sex
hormones in instructing adipocyte metabolic programs may help unravel the
mechanisms underlying gender dimorphism in liver cancer and identify the
metabolic targets for disease management.
DOI: 10.3389/fgene.2016.00168
PMCID: PMC5029146
PMID: 27703473
135. BMC Endocr Disord. 2018 May 31;18(1):34. doi: 10.1186/s12902-018-0262-2.
General health status in Iranian diabetic patients assessed by short-form-36
questionnaire: a systematic review and meta-analysis.

Behzadifar M(1), Sohrabi R(2), Mohammadibakhsh R(3), Salemi M(4), Moghadam ST(3),
Taheri Mirghaedm M(3), Behzadifar M(5), Baradaran HR(6), Bragazzi NL(7).
Author information:
(1)Social Determinants of Health Research Center, Lorestan University of Medical
Sciences, Khorramabad, Iran. masoudbehzadifar@gmail.com.
(2)Iranian Social Security Organization, Zanjan Province Health Administration,
Zanjan, Iran.
(3)Department of Health Services Management, School of Health Management and
Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
(4)Social Determinants in Health Promotion Research Center, Hormozgan University
of Medical Sciences, Bandar Abbas, Iran.
(5)Health Management and Economics Research Center, Iran University of Medical
Sciences, Tehran, Iran.
(6)Endocrine Research Center Institute of Endocrinology and Metabolism, Iran
(7)School of Public Health, Department of Health Sciences (DISSAL), University of
Genoa, Genoa, Italy.
BACKGROUND: Diabetes mellitus is one of the most prevalent diseases worldwide.
Diabetes is a chronic disease associated with micro- and macro-vascular
complications and deterioration in general health status. Therefore, the aim of
this study was to estimate general health status among Iranian diabetic patients
through a systematic review and meta-analysis of study utilizing the
Short-Form-36 questionnaire.
METHODS: Searching the EMBASE, PubMed, ISI/Web of Sciences (WOS), MEDLINE via
Ovid, PsycoINFO, as well as Iranian databases (MagIran, Iranmedex, and SID) from
January 2000 to December 2017. The methodological quality of the studies was
evaluated using the "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized
Studies of Interventions" (ACROBAT-NRSI). Random-effect model was used and the

means were reported with their 95% confidence interval (CI). To evaluate the
heterogeneity between studies, I2 test was used. Egger's regression test was used
to assess the publication bias.
RESULTS: Fourteen studies were retained in the final analysis. The mean general
health status using SF-36 in diabetic patients of Iran was 51.9 (95% CI: 48.64 to
53.54). The mean physical component summary was 52.92 [95% CI: 49.46-56.38],
while the mean mental component summary was 51.02 [95% CI: 46.87-55.16].
CONCLUSION: The findings of this study showed that general health status in
Iranian diabetic patients is low. Health policymakers should work to improve the
health status in these patients and take appropriate interventions.
DOI: 10.1186/s12902-018-0262-2
PMCID: PMC5984362
136. Front Physiol. 2016 Nov 22;7:560. eCollection 2016.
Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and
Inflammation in Diet-Induced Obesity.
Huang J(1), Rajapakse A(2), Xiong Y(2), Montani JP(1), Verrey F(3), Ming XF(1),
Yang Z(1).
Author information:
(1)Cardiovascular and Aging Research, Division of Physiology, Department of
Medicine, University of FribourgFribourg, Switzerland; Swiss National Centre of
Competence in Research (NCCR) Kidney Control of Homeostasis "Kidney.CH"Zurich,
Switzerland.
(2)Cardiovascular and Aging Research, Division of Physiology, Department of
Medicine, University of Fribourg Fribourg, Switzerland.

(3)Swiss National Centre of Competence in Research (NCCR) Kidney Control of
Homeostasis "Kidney.CH"Zurich, Switzerland; Institute of Physiology, University
of ZurichZurich, Switzerland.
Obesity is associated with development and progression of chronic kidney disease
(CKD). Recent evidence demonstrates that enhanced levels of the
L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and
arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of
endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical
anion and decreased NO production thereby endothelial dysfunction. Arg-II but not
Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is
uncertain and controversial. We aimed to investigate the role of Arg-II in renal
damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6
mice and mice deficient in Arg-II gene (Arg-II-/-) were fed with either a normal
chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks)
to induce obesity. In WT mice, HFD feeding caused frequent renal lipid
accumulation, enhancement of renal reactive oxygen species (ROS) levels which
could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney.
HFD feeding also significantly augmented renal Arg-II expression and activity.
All the alterations in the kidney under HFD feeding were reduced in Arg-II-/-
mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS)
staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and
intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by
immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no
significant difference in body weight and renal weight/body weight ratio between
the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney
of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage
associated with obesity, suggesting an important role of Arg-II in
obesity-associated renal disease development.
DOI: 10.3389/fphys.2016.00560
PMCID: PMC5118905
PMID: 27920727
137. Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
Genome-wide association analyses identify 143 risk variants and putative
regulatory mechanisms for type 2 diabetes.
Xue A(1), Wu Y(1), Zhu Z(1), Zhang F(1), Kemper KE(1), Zheng Z(1)(2), Yengo L(1),
Lloyd-Jones LR(1), Sidorenko J(1)(3), Wu Y(1); eQTLGen Consortium, McRae
AF(1)(4), Visscher PM(1)(4), Zeng J(5), Yang J(6)(7)(8).
Collaborators: Agbessi M, Ahsan H, Alves I, Andiappan A, Awadalla P, Battle A,
Beutner F, Bonder MJ, Boomsma D, Christiansen M, Claringbould A, Deelen P, Esko
T, Favé MJ, Franke L, Frayling T, Gharib S, Gibson G, Hemani G, Jansen R, Kähönen
M, Kalnapenkis A, Kasela S, Kettunen J, Kim Y, Kirsten H, Kovacs P, Krohn K,
Kronberg-Guzman J, Kukushkina V, Kutalik Z, Lee B, Lehtimäki T, Loeffler M,
Marigorta UM, Metspalu A, Milani L, Müller-Nurasyid M, Nauck M, Nivard M, Penninx
B, Perola M, Pervjakova N, Pierce B, Powell J, Prokisch H, Psaty B, Raitakari O,
Ring S, Ripatti S, Rotzschke O, Ruëger S, Saha A, Scholz M, Schramm K, Seppälä I,
Stumvoll M, Sullivan P, Teumer A, Thiery J, Tong L, Tönjes A, van Dongen J, van
Meurs J, Verlouw J, Völker U, Võsa U, Yaghootkar H, Zeng B.
Author information:
Queensland, 4072, Australia.
(2)The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical
University, Wenzhou, Zhejiang, 325027, China.
(3)Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu,
51010, Estonia.
(4)Queensland Brain Institute, The University of Queensland, Brisbane,
Queensland, 4072, Australia.
Queensland, 4072, Australia. j.zeng@uq.edu.au.
Queensland, 4072, Australia. jian.yang@uq.edu.au.
(7)The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical
University, Wenzhou, Zhejiang, 325027, China. jian.yang@uq.edu.au.
(8)Queensland Brain Institute, The University of Queensland, Brisbane,
Queensland, 4072, Australia. jian.yang@uq.edu.au.
Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a
meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic
variants in 62,892 T2D cases and 596,424 controls of European ancestry. We
identify 139 common and 4 rare variants associated with T2D, 42 of which (39
common and 3 rare variants) are independent of the known variants. Integration of
the gene expression data from blood (n = 14,115 and 2765) with the GWAS results
identifies 33 putative functional genes for T2D, 3 of which were targeted by
approved drugs. A further integration of DNA methylation (n = 1980) and
epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with
plausible regulatory mechanisms, whereby a genetic variant exerts an effect on
T2D through epigenetic regulation of gene expression. Our study uncovers
additional loci, proposes putative genetic regulatory mechanisms for T2D, and
provides evidence of purifying selection for T2D-associated variants.
DOI: 10.1038/s41467-018-04951-w
PMCID: PMC6063971
PMID: 30054458
138. PLoS Med. 2018 Jun 19;15(6):e1002581. doi: 10.1371/journal.pmed.1002581.

eCollection 2018 Jun.
Geographic and sociodemographic variation of cardiovascular disease risk in
India: A cross-sectional study of 797,540 adults.
Geldsetzer P(1), Manne-Goehler J(1)(2), Theilmann M(3)(4), Davies JI(5)(6),
Awasthi A(7)(8), Danaei G(1)(9), Gaziano TA(10)(11), Vollmer S(1)(3)(4), Jaacks
LM(1)(8), Bärnighausen T(1)(12)(13), Atun R(1)(14).
Author information:
(1)Department of Global Health and Population, Harvard T.H. Chan School of Public
Health, Harvard University, Boston, Massachusetts, United States of America.
(2)Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, Massachusetts, United States of America.
(3)Department of Economics, University of Goettingen, Göttingen, Germany.
(4)Centre for Modern Indian Studies, University of Goettingen, Göttingen,
Germany.
(5)MRC/Wits Rural Public Health and Health Transitions Research Unit, School of
Public Health, University of the Witwatersrand, Johannesburg, South Africa.
(6)Centre for Global Health, King's College London, London, United Kingdom.
(7)Indian Institute of Public Health, Gandhinagar, Gujarat, India.
(8)Public Health Foundation of India, Delhi, National Capital Region, India.
(9)Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard
University, Boston, Massachusetts, United States of America.
(10)Department of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts, United States of America.
(11)Center for Health Decision Science, Harvard T.H. Chan School of Public
Health, Boston, Massachusetts, United States of America.
(12)Institute of Public Health, Heidelberg University, Heidelberg, Germany.
(13)Africa Health Research Institute, Mtubatuba, South Africa.
(14)Department of Global Health and Social Medicine, Harvard Medical School,

Harvard University, Boston, Massachusetts, United States of America.
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in
India. Yet, evidence on the CVD risk of India's population is limited. To inform
health system planning and effective targeting of interventions, this study aimed
to determine how CVD risk-and the factors that determine risk-varies among states
in India, by rural-urban location, and by individual-level sociodemographic
characteristics.
METHODS AND FINDINGS: We used 2 large household surveys carried out between 2012
and 2014, which included a sample of 797,540 adults aged 30 to 74 years across
India. The main outcome variable was the predicted 10-year risk of a CVD event as
calculated with the Framingham risk score. The Harvard-NHANES, Globorisk, and
WHO-ISH scores were used in secondary analyses. CVD risk and the prevalence of
CVD risk factors were examined by state, rural-urban residence, age, sex,
household wealth, and education. Mean CVD risk varied from 13.2% (95% CI:
12.7%-13.6%) in Jharkhand to 19.5% (95% CI: 19.1%-19.9%) in Kerala. CVD risk
tended to be highest in North, Northeast, and South India. District-level wealth
quintile (based on median household wealth in a district) and urbanization were
both positively associated with CVD risk. Similarly, household wealth quintile
and living in an urban area were positively associated with CVD risk among both
sexes, but the associations were stronger among women than men. Smoking was more
prevalent in poorer household wealth quintiles and in rural areas, whereas body
mass index, high blood glucose, and systolic blood pressure were positively
associated with household wealth and urban location. Men had a substantially
higher (age-standardized) smoking prevalence (26.2% [95% CI: 25.7%-26.7%] versus
1.8% [95% CI: 1.7%-1.9%]) and mean systolic blood pressure (126.9 mm Hg [95% CI:
126.7-127.1] versus 124.3 mm Hg [95% CI: 124.1-124.5]) than women. Important
limitations of this analysis are the high proportion of missing values (27.1%) in
the main outcome variable, assessment of diabetes through a 1-time capillary
blood glucose measurement, and the inability to exclude participants with a
current or previous CVD event.

CONCLUSIONS: This study identified substantial variation in CVD risk among states
and sociodemographic groups in India-findings that can facilitate effective
targeting of CVD programs to those most at risk and most in need. While the CVD
risk scores used have not been validated in South Asian populations, the patterns
of variation in CVD risk among the Indian population were similar across all 4
risk scoring systems.
PMCID: PMC6007838
PMID: 29920517
interests exist.
139. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6.
Global, regional, and national incidence, prevalence, and years lived with
disability for 310 diseases and injuries, 1990-2015: a systematic analysis for
the Global Burden of Disease Study 2015.
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators.
Collaborators: Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A,
Casey DC, Charlson FJ, Chen AZ, Coggeshall M, Cornaby L, Dandona L, Dicker DJ,
Dilegge T, Erskine HE, Ferrari AJ, Fitzmaurice C, Fleming T, Forouzanfar MH,
Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Johnson CO, Kassebaum
NJ, Kawashima T, Kemmer L, Khalil IA, Kinfu Y, Kyu HH, Leung J, Liang X, Lim SS,
Lopez AD, Lozano R, Marczak L, Mensah GA, Mokdad AH, Naghavi M, Nguyen G, Nsoesie
E, Olsen H, Pigott DM, Pinho C, Rankin Z, Reinig N, Salomon JA, Sandar L, Smith
A, Stanaway J, Steiner C, Teeple S, Thomas BA, Troeger C, Wagner JA, Wang H,

Wanga V, Whiteford HA, Zoeckler L, Abajobir AA, Abate KH, Abbafati C, Abbas KM,
Abd-Allah F, Abraham B, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, Ackerman IN,
Adebiyi AO, Ademi Z, Adou AK, Afanvi KA, Agardh EE, Agarwal A, Kiadaliri AA,
Ahmadieh H, Ajala ON, Akinyemi RO, Akseer N, Al-Aly Z, Alam K, Alam NK, Aldhahri
SF, Alegretti MA, Alemu ZA, Alexander LT, Alhabib S, Ali R, Alkerwi A, Alla F,
Allebeck P, Al-Raddadi R, Alsharif U, Altirkawi KA, Alvis-Guzman N, Amare AT,
Amberbir A, Amini H, Ammar W, Amrock SM, Andersen HH, Anderson GM, Anderson BO,
Antonio CA, Aregay AF, Ärnlöv J, Artaman A, Asayesh H, Assadi R, Atique S,
Avokpaho EF, Awasthi A, Quintanilla BP, Azzopardi P, Bacha U, Badawi A,
Balakrishnan K, Banerjee A, Barac A, Barker-Collo SL, Bärnighausen T, Barregard
L, Barrero LH, Basu A, Bazargan-Hejazi S, Bell B, Bell ML, Bennett DA, Bensenor
IM, Benzian H, Berhane A, Bernabé E, Betsu BD, Beyene AS, Bhala N, Bhatt S,
Biadgilign S, Bienhoff K, Bikbov B, Biryukov S, Bisanzio D, Bjertness E, Blore J,
Borschmann R, Boufous S, Brainin M, Brazinova A, Breitborde NJ, Brown J,
Buchbinder R, Buckle GC, Butt ZA, Calabria B, Campos-Nonato IR, Campuzano JC,
Carabin H, Cárdenas R, Carpenter DO, Carrero JJ, Castañeda-Orjuela CA, Rivas JC,
Catalá-López F, Chang JC, Chiang PP, Chibueze CE, Chisumpa VH, Choi JJ, Chowdhury
R, Christensen H, Christopher DJ, Ciobanu LG, Cirillo M, Coates MM, Colquhoun SM,
Cooper C, Cortinovis M, Crump JA, Damtew SA, Dandona R, Daoud F, Dargan PI, das
Neves J, Davey G, Davis AC, Leo D, Degenhardt L, Del Gobbo LC, Dellavalle RP,
Deribe K, Deribew A, Derrett S, Jarlais DC, Dharmaratne SD, Dhillon PK,
Diaz-Torné C, Ding EL, Driscoll TR, Duan L, Dubey M, Duncan BB, Ebrahimi H,
Ellenbogen RG, Elyazar I, Endres M, Endries AY, Ermakov SP, Eshrati B, Estep K,
Farid TA, Farinha CS, Faro A, Farvid MS, Farzadfar F, Feigin VL, Felson DT,
Fereshtehnejad SM, Fernandes JG, Fernandes JC, Fischer F, Fitchett JR, Foreman K,
Fowkes FG, Fox J, Franklin RC, Friedman J, Frostad J, Fürst T, Futran ND, Gabbe
B, Ganguly P, Gankpé FG, Gebre T, Gebrehiwot TT, Gebremedhin AT, Geleijnse JM,
Gessner BD, Gibney KB, Ginawi IA, Giref AZ, Giroud M, Gishu MD, Glaser E, Godwin
WW, Gomez-Dantes H, Gona P, Goodridge A, Gopalani SV, Gotay CC, Goto A, Gouda HN,
Grainger R, Greaves F, Guillemin F, Guo Y, Gupta R, Gupta R, Gupta V, Gutiérrez
RA, Haile D, Hailu AD, Hailu GB, Halasa YA, Hamadeh RR, Hamidi S, Hammami M,
Hancock J, Handal AJ, Hankey GJ, Hao Y, Harb HL, Harikrishnan S, Haro JM,
Havmoeller R, Hay RJ, Heredia-Pi IB, Heydarpour P, Hoek HW, Horino M, Horita N,
Hosgood HD, Hoy DG, Htet AS, Huang H, Huang JJ, Huynh C, Iannarone M, Iburg KM,
Innos K, Inoue M, Iyer VJ, Jacobsen KH, Jahanmehr N, Jakovljevic MB, Javanbakht
M, Jayatilleke AU, Jee SH, Jeemon P, Jensen PN, Jiang Y, Jibat T, Jimenez-Corona
A, Jin Y, Jonas JB, Kabir Z, Kalkonde Y, Kamal R, Kan H, Karch A, Karema CK,
Karimkhani C, Kasaeian A, Kaul A, Kawakami N, Keiyoro PN, Kemp AH, Keren A,
Kesavachandran CN, Khader YS, Khan AR, Khan EA, Khang YH, Khera S, Khoja TA,
Khubchandani J, Kieling C, Kim P, Kim CI, Kim D, Kim YJ, Kissoon N, Knibbs LD,
Knudsen AK, Kokubo Y, Kolte D, Kopec JA, Kosen S, Kotsakis GA, Koul PA, Koyanagi
A, Kravchenko M, Defo BK, Bicer BK, Kudom AA, Kuipers EJ, Kumar GA, Kutz M, Kwan
GF, Lal A, Lalloo R, Lallukka T, Lam H, Lam JO, Langan SM, Larsson A, Lavados PM,
Leasher JL, Leigh J, Leung R, Levi M, Li Y, Li Y, Liang J, Liu S, Liu Y, Lloyd
BK, Lo WD, Logroscino G, Looker KJ, Lotufo PA, Lunevicius R, Lyons RA, Mackay MT,
Magdy M, Razek AE, Mahdavi M, Majdan M, Majeed A, Malekzadeh R, Marcenes W,
Margolis DJ, Martinez-Raga J, Masiye F, Massano J, McGarvey ST, McGrath JJ, McKee
M, McMahon BJ, Meaney PA, Mehari A, Mejia-Rodriguez F, Mekonnen AB, Melaku YA,
Memiah P, Memish ZA, Mendoza W, Meretoja A, Meretoja TJ, Mhimbira FA, Miller TR,
Mills EJ, Mirarefin M, Mitchell PB, Mock CN, Mohammadi A, Mohammed S, Monasta L,
Hernandez JC, Montico M, Mooney MD, Moradi-Lakeh M, Morawska L, Mueller UO,
Mullany E, Mumford JE, Murdoch ME, Nachega JB, Nagel G, Naheed A, Naldi L, Nangia
V, Newton JN, Ng M, Ngalesoni FN, Nguyen QL, Nisar MI, Pete PM, Nolla JM, Norheim
OF, Norman RE, Norrving B, Nunes BP, Ogbo FA, Oh IH, Ohkubo T, Olivares PR,
Olusanya BO, Olusanya JO, Ortiz A, Osman M, Ota E, Pa M, Park EK, Parsaeian M, de
Azeredo Passos VM, Caicedo AJ, Patten SB, Patton GC, Pereira DM, Perez-Padilla R,
Perico N, Pesudovs K, Petzold M, Phillips MR, Piel FB, Pillay JD, Pishgar F,
Plass D, Platts-Mills JA, Polinder S, Pond CD, Popova S, Poulton RG, Pourmalek F,
Prabhakaran D, Prasad NM, Qorbani M, Rabiee RH, Radfar A, Rafay A, Rahimi K,
Rahimi-Movaghar V, Rahman M, Rahman MH, Rahman SU, Rai RK, Rajsic S, Ram U, Rao
P, Refaat AH, Reitsma MB, Remuzzi G, Resnikoff S, Reynolds A, Ribeiro AL, Blancas
MJ, Roba HS, Rojas-Rueda D, Ronfani L, Roshandel G, Roth GA, Rothenbacher D, Roy
A, Sagar R, Sahathevan R, Sanabria JR, Sanchez-Niño MD, Santos IS, Santos JV,
Sarmiento-Suarez R, Sartorius B, Satpathy M, Savic M, Sawhney M, Schaub MP,
Schmidt MI, Schneider IJ, Schöttker B, Schwebel DC, Scott JG, Seedat S, Sepanlou
SG, Servan-Mori EE, Shackelford KA, Shaheen A, Shaikh MA, Sharma R, Sharma U,
Shen J, Shepard DS, Sheth KN, Shibuya K, Shin MJ, Shiri R, Shiue I, Shrime MG,
Sigfusdottir ID, Silva DA, Silveira DG, Singh A, Singh JA, Singh OP, Singh PK,
Sivonda A, Skirbekk V, Skogen JC, Sligar A, Sliwa K, Soljak M, Søreide K, Soriano
JB, Sposato LA, Sreeramareddy CT, Stathopoulou V, Steel N, Stein DJ, Steiner TJ,
Steinke S, Stovner L, Stroumpoulis K, Sunguya BF, Sur P, Swaminathan S, Sykes BL,
Szoeke CE, Tabarés-Seisdedos R, Takala JS, Tandon N, Tanne D, Tavakkoli M, Taye
B, Taylor HR, Ao BJ, Tedla BA, Terkawi AS, Thomson AJ, Thorne-Lyman AL, Thrift
AG, Thurston GD, Tobe-Gai R, Tonelli M, Topor-Madry R, Topouzis F, Tran BX,
Dimbuene ZT, Tsilimbaris M, Tura AK, Tuzcu EM, Tyrovolas S, Ukwaja KN, Undurraga
EA, Uneke CJ, Uthman OA, van Gool CH, Varakin YY, Vasankari T, Venketasubramanian
N, Verma RK, Violante FS, Vladimirov SK, Vlassov VV, Vollset SE, Wagner GR,
Waller SG, Wang L, Watkins DA, Weichenthal S, Weiderpass E, Weintraub RG,
Werdecker A, Westerman R, White RA, Williams HC, Wiysonge CS, Wolfe CD, Won S,
Woodbrook R, Wubshet M, Xavier D, Xu G, Yadav AK, Yan LL, Yano Y, Yaseri M, Ye P,
Yebyo HG, Yip P, Yonemoto N, Yoon SJ, Younis MZ, Yu C, Zaidi Z, Zaki ME, Zeeb H,
Zhou M, Zodpey S, Zuhlke LJ, Murray CJ.
Erratum in
Lancet. 2017 Jan 7;389(10064):e1.
Comment in
Lancet. 2017 Jan 7;389(10064):18-19.
Comment on
Lancet. 2016 Oct 8;388(10053):1450-1452.
Lancet. 2016 Oct 8;388(10053):1448-1449.

BACKGROUND: Non-fatal outcomes of disease and injury increasingly detract from
the ability of the world's population to live in full health, a trend largely
attributable to an epidemiological transition in many countries from causes
affecting children, to non-communicable diseases (NCDs) more common in adults.
For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD
2015), we estimated the incidence, prevalence, and years lived with disability
for diseases and injuries at the global, regional, and national scale over the
period of 1990 to 2015.
METHODS: We estimated incidence and prevalence by age, sex, cause, year, and
geography with a wide range of updated and standardised analytical procedures.
Improvements from GBD 2013 included the addition of new data sources, updates to
literature reviews for 85 causes, and the identification and inclusion of
additional studies published up to November, 2015, to expand the database used
for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence
and incidence by cause and sequelae were determined with DisMod-MR 2.1, an
improved version of the DisMod-MR Bayesian meta-regression tool first developed
for GBD 2010 and GBD 2013. For some causes, we used alternative modelling
strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or
where incidence and prevalence needed to be determined from other data. For GBD
2015 we created a summary indicator that combines measures of income per capita,
educational attainment, and fertility (the Socio-demographic Index [SDI]) and
used it to compare observed patterns of health loss to the expected pattern for
countries or locations with similar SDI scores.
FINDINGS: We generated 9·3 billion estimates from the various combinations of
prevalence, incidence, and YLDs for causes, sequelae, and impairments by age,
sex, geography, and year. In 2015, two causes had acute incidences in excess of 1
billion: upper respiratory infections (17·2 billion, 95% uncertainty interval
[UI] 15·4-19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30-2·50
billion). Eight causes of chronic disease and injury each affected more than 10%
of the world's population in 2015: permanent caries, tension-type headache,
iron-deficiency anaemia, age-related and other hearing loss, migraine, genital

herpes, refraction and accommodation disorders, and ascariasis. The impairment
that affected the greatest number of people in 2015 was anaemia, with 2·36
billion (2·35-2·37 billion) individuals affected. The second and third leading
impairments by number of individuals affected were hearing loss and vision loss,
respectively. Between 2005 and 2015, there was little change in the leading
causes of years lived with disability (YLDs) on a global basis. NCDs accounted
for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where
rates were decreasing, the rate of decrease for YLDs was slower than that of
years of life lost (YLLs) for nearly every cause included in our analysis. For
low SDI geographies, Group 1 causes typically accounted for 20-30% of total
disability, largely attributable to nutritional deficiencies, malaria, neglected
tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the
leading global cause of disability in 2015 in most countries. The leading cause
was sense organ disorders in 22 countries in Asia and Africa and one in central
Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern
sub-Saharan African countries; collective violence and legal intervention in two
north African and Middle Eastern countries; iron-deficiency anaemia in Somalia
and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other
neglected tropical diseases in the Democratic Republic of the Congo.
INTERPRETATION: Ageing of the world's population is increasing the number of
people living with sequelae of diseases and injuries. Shifts in the
epidemiological profile driven by socioeconomic change also contribute to the
continued increase in years lived with disability (YLDs) as well as the rate of
increase in YLDs. Despite limitations imposed by gaps in data availability and
the variable quality of the data available, the standardised and comprehensive
approach of the GBD study provides opportunities to examine broad trends, compare
those trends between countries or subnational geographies, benchmark against
locations at similar stages of development, and gauge the strength or weakness of
the estimates available.
FUNDING: Bill & Melinda Gates Foundation.

Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.
DOI: 10.1016/S0140-6736(16)31678-6
PMCID: PMC5055577
140. Cardiol Clin. 2017 Feb;35(1):1-12. doi: 10.1016/j.ccl.2016.08.004.
Global Shifts in Cardiovascular Disease, the Epidemiologic Transition, and Other
Contributing Factors: Toward a New Practice of Global Health Cardiology.
Mendoza W(1), Miranda JJ(2).
Author information:
(1)United Nations Population Fund, Peru Country Office, Av. Guardia Civil 1231,
San Isidro, Lima 27, Peru.
(2)School of Medicine, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado
430, Urb. Ingeniería, San Martín de Porres, Lima 31, Peru; CRONICAS Center of
Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Av.
Armendáriz 497, Miraflores, Lima 18, Peru. Electronic address:
Jaime.Miranda@upch.pe.
One of the major drivers of change in the practice of cardiology is population
change. This article discusses the current debate about epidemiologic transition
paired with other ongoing transitions with direct relevance to cardiovascular
conditions. Challenges specific to patterns of risk factors over time; readiness
for disease surveillance and meeting global targets; health system, prevention,
and treatment efforts; and physiologic traits and human-environment interactions
are identified. This article concludes that a focus on the most populated regions
of the world will contribute substantially to protecting the large gains in
global survival and life expectancy accrued over the last decades.
Copyright Â© 2016 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ccl.2016.08.004
PMCID: PMC5134924
Conflict of interest statement: Financial conflicts of interest The authors have
nothing to disclose.
141. Diabetes Ther. 2017 Apr;8(2):335-353. doi: 10.1007/s13300-017-0237-8. Epub 2017
Feb 24.
Glucagon-Like Peptide-1 Receptor Agonist Treatment Attributes Important to
Injection-Experienced Patients with Type 2 Diabetes Mellitus: A Preference Study
in Germany and the United Kingdom.
Qin L(1), Chen S(2), Flood E(3), Shaunik A(2), Romero B(3), de la Cruz M(3),
Alvarez C(4), Grandy S(2).
Author information:
(1)AstraZeneca, Gaithersburg, MD, USA. lei.qin@astrazeneca.com.
(2)AstraZeneca, Gaithersburg, MD, USA.
(3)ICON plc, Clinical Outcomes Assessment, Gaithersburg, MD, USA.
(4)ICON plc, Medical Affairs Statistical Analysis, San Diego, CA, USA.
INTRODUCTION: This study assessed the relative importance of treatment-related
attributes in influencing patient preferences for glucagon-like peptide-1

receptor agonists (GLP-1RAs) among injection-experienced type 2 diabetes mellitus
(T2DM) patients in Germany and the United Kingdom.
METHODS: T2DM patients experienced with injecting once-weekly (QW) exenatide or
once-daily (QD) liraglutide completed an online discrete-choice experiment (DCE)
survey. Patients chose between hypothetical blinded treatment profiles reflecting
attributes of GLP-1RAs. The DCE survey included eight attributes: efficacy, side
effects, device size, needle size, titration, injection preparation, long-term
efficacy/safety, and dosing frequency. Odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated using a conditional logit model indicating the
likelihood of choosing a treatment with a given attribute level versus a
reference attribute level.
RESULTS: 510 GLP-1RA injection-experienced patients completed the survey; 45.3%
respondents were being treated with exenatide QW and 54.7% respondents were being
treated with liraglutide QD. In terms of GLP-1RA attributes, patients indicated a
preference for a treatment with greater efficacy (i.e., a 1.5-point improvement
in HbA1c) (OR 2.58; 95% CI 2.37, 2.80; p < 0.001), fewer side effects (OR 2.67;
95% CI 2.52, 2.82; p < 0.001), once-weekly rather than once-daily administration
(OR 2.26; 95% CI 2.13, 2.39; p < 0.001), and the preparation required for a
multi-use pen (OR 1.71; 95% CI 1.55, 1.88; p < 0.001). Needle size, device size,
and titration were not significant drivers of patient preference.
CONCLUSIONS: Among GLP-1RA injection-experienced patients, key drivers of
treatment preference for a hypothetical GLP-RA profile were side effects,
efficacy, dosing frequency, and required preparation. Understanding patient
preferences is important for optimizing treatment decision-making and improving
treatment adherence.
FUNDING: AstraZeneca.
DOI: 10.1007/s13300-017-0237-8
PMCID: PMC5380499
PMID: 28236271
142. PLoS One. 2018 Jun 7;13(6):e0198626. doi: 10.1371/journal.pone.0198626.
eCollection 2018.
Glutathione metabolism in type 2 diabetes and its relationship with microvascular
complications and glycemia.
Lutchmansingh FK(1), Hsu JW(2), Bennett FI(3), Badaloo AV(4), McFarlane-Anderson
N(1), Gordon-Strachan GM(5), Wright-Pascoe RA(6), Jahoor F(2), Boyne MS(4)(6).
Author information:
(1)Department of Basic Medical Sciences, The University of the West Indies, Mona,
Jamaica.
(2)Children's Nutrition Research Center, Department of Pediatrics, Baylor College
of Medicine, Houston, Texas, United States of America.
(3)Department of Pathology, University Hospital of the West Indies; Mona,
Jamaica.
(4)Caribbean Institute for Health Research, The University of the West Indies,
Mona, Jamaica.
(5)Health Research Unit, Faculty of Medical Sciences, The University of the West
Indies, Mona, Jamaica.
(6)Department of Medicine, The University of the West Indies, Mona, Jamaica.
AIMS/HYPOTHESES: We hypothesized that there is decreased synthesis of glutathione
(GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular
complications, and this is dependent on the degree of hyperglycemia.
METHODS: In this case-control study, we recruited 16 patients with T2DM (7
without and 9 with microvascular complications), and 8 age- and sex-matched
non-diabetic controls. We measured GSH synthesis rate using an infusion of
[2H2]-glycine as isotopic tracer and collection of blood samples for liquid
chromatography mass spectrometric analysis.

RESULTS: Compared to the controls, T2DM patients had lower erythrocyte GSH
concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute
synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not
fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes
of changes in patients with complications were greater for both GSH
concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to
controls. There were no differences in GSH concentrations and synthesis rates
between T2DM patients with and without complications (P-values > 0.1). Fasting
glucose and HbA1c did not correlate with GSH concentration or synthesis rates
(P-values > 0.17).
CONCLUSIONS: Compared to non-diabetic controls, patients with T2DM have
glutathione deficiency, especially if they have microvascular complications. This
is probably due to reduced synthesis and increased irreversible utilization by
non-glycemic mechanisms.
PMCID: PMC5991679
PMID: 29879181
interests exist.
143. Diabet Med. 2017 Jun;34(6):804-812. doi: 10.1111/dme.13335.
Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in
sea-level and high-altitude settings.
Bazo-Alvarez JC(1), Quispe R(1), Pillay TD(1)(2), Bernabé-Ortiz A(1), Smeeth
L(1)(3), Checkley W(1)(4), Gilman RH(1)(5)(6), Málaga G(1)(7), Miranda JJ(1)(7).

Author information:
(1)CRONICAS Centre of Excellence in Chronic Diseases, Universidad Peruana
(2)University College London Medical School, London School of Hygiene and
(4)Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore,
MD, USA.
(5)Área de Investigación y Desarrollo, A.B. PRISMA, Lima, Peru.
(6)Department of International Health, Johns Hopkins Bloomberg School of Public
Health, Johns Hopkins University, Baltimore, MD, USA.
(7)Department of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
AIM: Higher haemoglobin levels and differences in glucose metabolism have been
reported among high-altitude residents, which may influence the diagnostic
performance of HbA1c . This study explores the relationship between HbA1c and
fasting plasma glucose (FPG) in populations living at sea level and at an
altitude of > 3000 m.
METHODS: Data from 3613 Peruvian adults without a known diagnosis of diabetes
from sea-level and high-altitude settings were evaluated. Linear, quadratic and
cubic regression models were performed adjusting for potential confounders.
Receiver operating characteristic (ROC) curves were constructed and concordance
between HbA1c and FPG was assessed using a Kappa index.
RESULTS: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05)
for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA1c ;
and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The
adjusted relationship between HbA1c and FPG was quadratic at sea level and linear
at high altitude. Adjusted models showed that, to predict an HbA1c value of
48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high
altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA1c
cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95%
confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to
63.6) at high altitude.
CONCLUSION: The relationship between HbA1c and FPG is less clear at high altitude
than at sea level. Caution is warranted when using HbA1c to diagnose diabetes
mellitus in this setting.
DOI: 10.1111/dme.13335
PMCID: PMC5432378
144. Clin Infect Dis. 2017 Nov 29;65(12):2060-2068. doi: 10.1093/cid/cix632.
Glycemic Control and the Prevalence of Tuberculosis Infection: A Population-based
Observational Study.
Martinez L(1)(2), Zhu L(3), Castellanos ME(1)(2), Liu Q(3), Chen C(3)(4)(5),
Hallowell BD(1)(2), Whalen CC(1)(2).
Author information:
(1)Department of Epidemiology and Biostatistics.
(2)Center for Global Health, College of Public Health, University of Georgia,
Athens.
(3)Department of Chronic Communicable Disease, Center for Disease Control and
Prevention of Jiangsu Province, Nanjing, People's Republic of China.
(4)Key Laboratory of Public Health Safety, Ministry of Education.
(5)School of Public Health, Fudan University, Shanghai, China.

Background: Several cohort studies demonstrate that diabetics are at increased
risk for active tuberculosis, and poor glycemic control may exacerbate this risk.
A higher prevalence of tuberculosis infection at baseline among diabetics may
partially explain these results; however, no population-based studies have
investigated this association. Furthermore, whether glycemic control modifies the
relationship between diabetes and tuberculosis infection, as it does with active
tuberculosis, is unknown.
Methods: Diabetics were diagnosed through physician evaluation and using 3
laboratory tests including hemoglobin A1C (HbA1C), fasting plasma glucose (FPG),
or 2-hour plasma glucose (PG). Tuberculosis infection was diagnosed through
tuberculin skin tests, and glycemic control was assessed linearly and
categorically using recommended targets.
Results: Among 4215 participants, the prevalence of tuberculosis infection was
4.1%, 5.5%, and 7.6% in nondiabetic, prediabetic, and diabetic participants
(Ptrend = .012). In multivariate analysis, diabetes was associated with
tuberculosis infection (adjusted odds ratio [AOR], 1.5; 95% confidence interval
[CI], 1.0-2.2). Compared to nondiabetics, diabetics who were undiagnosed (AOR,
2.2 and 1.2 in diagnosed diabetics), FPG >130 mg/dL (AOR, 2.6 and 1.3 in
diabetics with FPG ≤130 mg/dL), or not on insulin (AOR, 1.7 and 0.8 in diabetics
on insulin) had elevated tuberculosis infection rates. In a linear dose-response
analysis, increasing values of FPG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.03), PG
(AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.04), and HbA1C (AOR, 1.13 per 1%; 95% CI,
1.04-1.22) all predicted tuberculosis infection.
Conclusions: Our results suggest glycemic control may modify the relationship
between tuberculosis infection and diabetes.
Diseases Society of America. All rights reserved. For permissions, e-mail:
journals.permissions@oup.com.
DOI: 10.1093/cid/cix632
145. Nutrients. 2017 Oct 4;9(10). pii: E1095. doi: 10.3390/nu9101095.
Glycemic Response to Black Beans and Chickpeas as Part of a Rice Meal: A
Randomized Cross-Over Trial.
Winham DM(1), Hutchins AM(2), Thompson SV(3).
Author information:
(1)Department of Food Science & Human Nutrition, Iowa State University, Ames, IA
50011, USA. dwinham@iastate.edu.
(2)Department of Health Sciences, University of Colorado Colorado Springs,
Colorado Springs, CO 80918, USA. Andrea.Hutchins@uccs.edu.
(3)Division of Nutritional Sciences, University of Illinois at Urbana Champaign,
Urbana, IL 61801, USA;. svthomp2@illinois.edu.
Legumes, such as black beans (Phaseolus vulgaris L.) and chickpeas (Cicer
arietinum L.), have a low glycemic index, and may reduce the glycemic load of
meals in which they are included. Although the low glycemic response of beans
consumed alone has been documented, few studies have examined the glycemic
response to traditional food combinations such as black beans and rice or
chickpeas and rice. This randomized cross-over study examined the glycemic and
insulinemic impact of 50 grams of available carbohydrate from three test meals:
plain white rice (control), black beans with rice, and chickpeas with rice among
healthy adult women (n = 12, 18-65 years). Treatments were consumed on different
mornings, a minimum of 7 days apart. Blood samples were collected at time 0
(fasting), and at 30, 60, 90, and 120 min postprandial, and were subsequently
analyzed for glucose and insulin concentrations. Glucose response based on the
incremental area under the curve showed a significant difference by treatment (p
= 0.027). Changes in blood glucose concentrations were significantly different
for the black bean meal and the chickpea meal in comparison to rice alone at 60
min (p = 0.026 and p = 0.024), 90 min (p = 0.001 and p = 0.012) and 120 min post
prandial (p = 0.024; black bean meal). Findings indicate that combinations of
black beans and chickpeas with white rice improve glycemic response, providing
evidence that has promising implications for dietary guidance to reduce
postprandial glucose and related health risks through traditional food patterns.
DOI: 10.3390/nu9101095
PMCID: PMC5691712
Conflict of interest statement: The authors declare no conflict of interest
146. Cell Metab. 2017 Jun 6;25(6):1216-1230. doi: 10.1016/j.cmet.2017.04.033.
A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism.
Mauvais-Jarvis F(1), Arnold AP(2), Reue K(3).
Author information:
(1)Diabetes Discovery & Gender Medicine Laboratory, Section of Endocrinology &
Metabolism, Department of Medicine, Tulane University Health Sciences Center, New
Orleans, LA 70112, USA. Electronic address: fmauvais@tulane.edu.
(2)Department of Integrative Biology & Physiology, University of California, Los
Angeles, CA 90095, USA.
(3)Department of Human Genetics, David Geffen School of Medicine, University of
California, Los Angeles, CA 90095, USA.

In animal models, the physiological systems involved in metabolic homeostasis
exhibit a sex difference. Investigators often use male rodents because they show
metabolic disease better than females. Thus, females are not used precisely
because of an acknowledged sex difference that represents an opportunity to
understand novel factors reducing metabolic disease more in one sex than the
other. The National Institutes of Health (NIH) mandate to consider sex as a
biological variable in preclinical research places new demands on investigators
and peer reviewers who often lack expertise in model systems and experimental
paradigms used in the study of sex differences. This Perspective discusses
experimental design and interpretation in studies addressing the mechanisms of
sex differences in metabolic homeostasis and disease, using animal models and
cells. We also highlight current limitations in research tools and attitudes that
threaten to delay progress in studies of sex differences in basic animal
research.
Copyright © 2017 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cmet.2017.04.033
PMCID: PMC5516948
147. Pediatr Diabetes. 2018 May;19(3):375-380. doi: 10.1111/pedi.12596. Epub 2017 Oct
30.
Handgrip strength is associated with insulin resistance and glucose metabolism in
adolescents: Evidence from National Health and Nutrition Examination Survey 2011
to 2014.
Li S(1), Zhang R(2), Pan G(2), Zheng L(3), Li C(4).

Author information:
(1)Department of Epidemiology, Tulane School of Public Health and Tropical
Medicine, New Orleans, Louisiana.
(2)Institute of Chronic Disease, Liaoning Provincial Center for Disease Control
and Prevention, Shenyang, China.
(3)Department of Clinical Epidemiology, Shengjing Hospital of China Medical
University, Shenyang, China.
(4)Department of Epidemiology and Biostatistics, University of Georgia College of
Public Health, Athens, Georgia, USA.
BACKGROUND: Previous studies have reported that handgrip strength, a measure of
muscular fitness, is associated with insulin resistance in children and
adolescents, with conflicting results. Further, no studies have examined the
association between handgrip strength with 2-hour glucose levels.
OBJECTIVE: We tested the association of handgrip strength with measures of
insulin resistance (fasting insulin and homeostasis model assessment of insulin
resistance [HOMA-IR]) and glucose metabolism (fasting and 2-hour glucose levels)
in adolescents from the National Health and Nutrition Examination Survey (NHANES)
2011 to 2014.
METHODS: The study included 959 participants aged 12 to 19 years who underwent a
handgrip test and a glucose tolerance test. General linear models were used to
examine the associations between handgrip strength and the outcome variables.
RESULTS: After adjustment for age, race, sex, body mass index, and physical
activities, handgrip strength was inversely associated with fasting insulin
levels (P = .017) and HOMA-IR (P = .025). Although there was no association
between handgrip strength and fasting glucose levels (P = .77), handgrip strength
was inversely associated with 2-hour glucose levels (P < .0001). Insulin and
2-hour glucose levels decreased linearly as handgrip strength increased from the
bottom quartile to the top quartile (P for trend: .045 for fasting insulin levels
and .004 for 2-hour glucose levels).

CONCLUSIONS: Muscular fitness, measured by handgrip strength, is associated with
insulin resistance and glucose metabolism in adolescents, which indicates that
increasing muscular fitness may have beneficial effects for early prevention of
insulin resistance and type 2 diabetes.
DOI: 10.1111/pedi.12596
148. Clin Diabetes. 2018 Apr;36(2):160-167. doi: 10.2337/cd17-0063.
Health Care Providers' Perceptions of Responsibilities and Resources to Reduce
Type 2 Diabetes Risk After Gestational Diabetes Mellitus.
Hewage SS(1), Singh SR(1), Chi C(2), Chan JKY(3)(4), Yew TW(5), Han WM(6), Yoong
J(1)(7).
Author information:
Singapore.
(2)Department of Obstetrics and Gynecology, National University Hospital,
Singapore.
(3)Duke-NUS Medical School, Singapore.
(4)Department of Reproductive Medicine, KK Women's and Children's Hospital,
Singapore.
(5)University Medicine Cluster, National University Health System, Singapore.
(6)Nutrition and Dietetics Department, KK Women's and Children's Hospital,
Singapore.
(7)University of Southern California, Center for Economic and Social Research,
Los Angeles, CA.
IN BRIEF Gestational diabetes mellitus (GDM) increases the risk for type 2
diabetes. This qualitative study aimed to evaluate health care providers'
perceptions of care responsibilities and resources related to reducing type 2
diabetes risk among women with previous GDM in Singapore. Health care providers
acknowledged a shared responsibility. They felt that they had less understanding
of compliance with long-term maintenance of lifestyle change, exacerbated further
by fragmentation of follow-up care. The application of more integrated
patient-centered care models, combined with greater health literacy, is urgently
required in this area.
DOI: 10.2337/cd17-0063
PMID: 29686455
149. Patient Prefer Adherence. 2018 May 9;12:765-773. doi: 10.2147/PPA.S165203.
eCollection 2018.
Health-related quality of life in type 2 diabetes mellitus patients with
different risk for obstructive sleep apnea.
Gabric K(#)(1)(2), Matetic A(#)(1), Vilovic M(1), Ticinovic Kurir T(1), Rusic
D(3), Galic T(4), Jonjic I(2), Bozic J(1).
Author information:
(1)Department of Pathophysiology, University of Split School of Medicine, Split,
Croatia.
(2)University Eye Hospital Svjetlost, Zagreb, Croatia.

(3)Department of Pharmacy, University of Split School of Medicine, Split,
Croatia.
(4)Study of Dental Medicine, University of Split School of Medicine, Split,
Croatia.
(#)Contributed equally
Purpose: Our study primarily aimed to investigate health-related quality of life
(HRQoL) in type 2 diabetes mellitus (T2DM) patients with different risk for
obstructive sleep apnea (OSA).
Patients and methods: This cross-sectional, questionnaire-based study included
466 adult patients with T2DM on regular visit to Center for Diabetes of
University Hospital of Split from April to September 2017. All subjects underwent
detailed anamnestical evaluation and physical examination with anthropometric
measurements. Additionally, all subjects completed STOP (Snoring, Tiredness,
Observed apnea, and high blood Pressure) questionnaire to assess risk for OSA,
Epworth Sleepiness Scale to assess daytime sleepiness, and Medical Outcomes Study
Short Form-36 (SF-36) instrument to evaluate HRQoL.
Results: Most subjects (N=312, 67.0%) represented high-risk OSA group based on
STOP questionnaire (STOP score ≥2). Statistically significantly lower HRQoL
scores in all SF-36 dimensions were found in T2DM patients with high risk for OSA
compared to low-risk group (P<0.001). STOP score showed statistically significant
negative correlation with all SF-36 dimensions (P<0.001). In multiple linear
regression analysis, STOP score was confirmed as statistically significant
independent predictor for all SF-36 components, adjusted for body mass index,
age, glycated hemoglobin, and T2DM duration (P<0.001).
Conclusion: Our study found that high proportion of patients with T2DM are at
high risk for OSA. Furthermore, we showed that group of T2DM patients with high
risk for OSA has lower HRQoL in all SF-36 dimensions compared to low-risk
patients.
DOI: 10.2147/PPA.S165203
PMCID: PMC5953311
PMID: 29785091
150. Biodemography Soc Biol. 2018 Jan-Mar;64(1):43-62. doi:
10.1080/19485565.2018.1451300.
HPLC-based Measurement of Glycated Hemoglobin using Dried Blood Spots Collected
under Adverse Field Conditions.
Thomas D(1), Seeman T(2), Potter A(3), Hu P(2), Crimmins E(4), Herningtyas EH(5),
Sumantri C(6), Frankenberg E(7).
Author information:
(1)a Economics Department and Duke Global Health Institute , Duke University ,
Durham , NC , USA.
(2)b David Geffen School of Medicine , University of California , Los Angeles ,
CA , USA.
(3)c Department of Laboratory Medicine , University of Washington , Seattle , WA
, USA.
(4)d Leonard Davis School of Gerontology , University of Southern California ,
Los Angeles , CA , USA.
(5)e Department of Clinical Pathology and Laboratory Medicine, Faculty of
Medicine , Public Health and Nursing, Universitas Gadjah Mada , Yogyakarta ,
Indonesia.
(6)f SurveyMETER , Yogyakarta , Indonesia.
(7)g Sociology Department and Carolina Population Center , University of North
Carolina , Chapel Hill , NC , USA.

Glycated hemoglobin (HbA1c) measured using high-performance liquid chromatography
(HPLC) assays with venous blood and dried blood spots (DBS) are compared for 143
paired samples collected in Aceh, Indonesia. Relative to gold-standard
venous-blood values, DBS-based values reported by the HPLC are systematically
upward biased for HbA1c<8% and the fraction diabetic (HbA1c ≥ 6.5%) is overstated
almost five-fold. Inspection of chromatograms from DBS assays indicates the %
glycosylated calculated by the HPLC excludes part of the hemoglobin A which is
misidentified as a hemoglobin variant. Taking this into account, unbiased
DBS-based values are computed using data from the machine-generated
chromatograms. When the DBS are collected in a clinic-like setting, under
controlled humidity/temperature conditions, the recalculated values are almost
identical to venous-based values. When DBS are collected under field conditions,
the recalculated values are unbiased, but only about half the HbA1c values are
measured reliably, calling into question the validity of the other half. The
results suggest that collection conditions, particularly humidity, affect the
quality of the DBS-based measures. Cross-validating DBS-based HbA1c values with
venous samples collected under exactly the same environmental conditions is a
prudent investment in population-based studies.
DOI: 10.1080/19485565.2018.1451300
PMID: 29741414
151. Oncotarget. 2017 Oct 26;8(65):108655-108664. doi: 10.18632/oncotarget.22094.
eCollection 2017 Dec 12.
Hyperglycemia combined Helicobacter pylori infection increases risk of
synchronous colorectal adenoma and carotid artery plaque.

Hu KC(1)(2)(3)(4)(5), Wu MS(4)(6), Chu CH(1)(3), Wang HY(1)(2)(3), Lin SC(1)(3),
Po HL(7), Bair MJ(8), Liu CC(2), Su TH(6), Chen CL(4), Liu CJ(4)(6), Shih
SC(1)(2)(3)(5).
Author information:
(1)Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial
(2)Healthy Evaluation Center, MacKay Memorial Hospital, Taipei, Taiwan.
(3)MacKay Medicine, Nursing and Management College, Taipei, Taiwan.
(4)Graduate Institute of Clinical Medicine, National Taiwan University College of
Medicine, Taipei, Taiwan.
(5)MacKay Medical College, Taipei, Taiwan.
(6)Department of Internal Medicine, National Taiwan University Hospital, National
Taiwan University College of Medicine, Taipei, Taiwan.
(7)Department of Neurology, MacKay Memorial Hospital, Taipei, Taiwan.
(8)Gastroenterology Division, Department of Internal Medicine, MacKay Memorial
Hospital, Taitung Branch, Taiwan.
Background: Cardiovascular disease and colorectal cancer have severe consequences
to human health and may occur simultaneously or sequentially. Carotid artery
plaque is a predictor of cardiovascular disease, and colorectal adenoma is a
premalignant lesion of colorectal cancer. We investigated the core risk factors
of carotid artery plaque and colorectal adenoma.
Results: In total, 2361 subjects were enrolled. In multivariate analysis, age ≥
60 years, male sex, BMI > 27, LDL > 130 mg/dL, HbA1c ≥ 6.5%, hs-CRP > 0.3 mg/L
and H. pylori infection were independent risk factors for synchronous colorectal
adenoma and carotid artery plaque formation. In the H. pylori-positive and
-negative groups, the proportions and odds ratio (OR) for synchronous colon
adenoma and carotid artery plaque increased with increasing HbA1c. OR for
synchronous colon adenoma and carotid artery plaque was significantly higher in
the participants with HbA1c levels of 5.7%-6.4% and HbA1c ≥ 6.5% than in those
with normal HbA1c in the H. pylori-negative group. The OR was more significant
increased for H. pylori-positive patients when HbA1c level ≥ 6.5% was 15.87 (95%
CI 8.661-29.082, p < 0.0001).
Materials and Methods: The records of 4669 subjects aged > 40 years who underwent
bidirectional gastrointestinal endoscopy and carotid artery ultrasound
examination on the same day or within 12 months of endoscopy examination from
January 2006 to December 2015 were reviewed. All subjects had a gastric biopsy
specimen tested for Helicobacter pylori.
Conclusions: Hyperglycemia combined with H. pylori infection was an increased
risk factor for synchronous colorectal adenoma and carotid artery plaque
formation. Diabetes control and H. pylori eradication may be warranted in higher
prevalence areas.
DOI: 10.18632/oncotarget.22094
PMCID: PMC5752471
PMID: 29312558
Conflict of interest statement: CONFLICTS OF INTEREST All authors have no any
potential conflicts (financial, professional, or personal) that are relevant to
the manuscript.
152. Diabetes Spectr. 2018 Aug;31(3):218-224. doi: 10.2337/ds17-0085.
Hypertension Management in Diabetes: 2018 Update.
Passarella P(1), Kiseleva TA(2), Valeeva FV(2), Gosmanov AR(1)(3).
Author information:
(1)Department of Medicine, Division of Endocrinology, Albany Medical College,
Albany, NY.
(2)Department of Endocrinology, Kazan State Medical University, Kazan, Russia.
(3)Section of Endocrinology, Stratton VA Medical Center, Albany, NY.
IN BRIEF Several guidelines and position statements are published to help
clinicians manage hypertension in patients with diabetes. Although there is an
unequivocal call to treat hypertension in diabetes, professional organizations
and experts have differing opinions regarding the most optimal blood pressure
targets and treatments to lower vascular risks in the diabetes population. The
objective of this article is to summarize the most recent hypertension management
guidelines with particular attention to the origins and evidence behind these
recommendations.
DOI: 10.2337/ds17-0085
PMID: 30140137
153. J Clin Invest. 2018 Jan 2;128(1):309-322. doi: 10.1172/JCI89333. Epub 2017 Nov
27.
Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote
obesity-induced insulin resistance.
Tanigaki K(1), Sacharidou A(1), Peng J(1), Chambliss KL(1), Yuhanna IS(1), Ghosh
D(2)(3), Ahmed M(1), Szalai AJ(4), Vongpatanasin W(5), Mattrey RF(3), Chen Q(6),
Azadi P(6), Lingvay I(7), Botto M(8), Holland WL(9), Kohler JJ(10), Sirsi
SR(2)(3), Hoyt K(2)(3), Shaul PW(1), Mineo C(1).
Author information:
(1)Center for Pulmonary and Vascular Biology, Department of Pediatrics,
University of Texas Southwestern Medical Center, Dallas, Texas, USA.

(2)Department of Bioengineering, University of Texas at Dallas, Richardson Texas,
USA.
(3)Department of Radiology, University of Texas Southwestern Medical Center,
Dallas, Texas, USA.
(4)Division of Clinical Immunology and Rheumatology, Department of Medicine,
University of Alabama at Birmingham, Birmingham, Alabama, USA.
(5)Hypertension Section, Division of Cardiology, Department of Internal Medicine,
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
(6)The Complex Carbohydrate Research Center, University of Georgia, Athens,
Georgia, USA.
(7)Division of Endocrinology, Diabetes, and Metabolism and Department of Clinical
Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
(8)Centre for Complement and Inflammation Research, Division of Immunology and
Inflammation, Department of Medicine, Imperial College London, London, United
Kingdom.
(9)Touchstone Diabetes Center, Department of Internal Medicine, and.
(10)Department of Biochemistry, University of Texas Southwestern Medical Center,
Dallas, Texas, USA.
Type 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we
have shown that activation of the IgG receptor FcγRIIB in endothelium by
hyposialylated IgG plays an important role in obesity-induced insulin resistance.
Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or
selectively in endothelium were protected from insulin resistance as a result of
the preservation of insulin delivery to skeletal muscle and resulting maintenance
of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as
the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin
resistance. Moreover, IgG transferred from patients with T2DM but not from
metabolically healthy subjects caused insulin resistance in IgG-deficient mice
via FcγRIIB, indicating that similar processes may be operative in T2DM in
humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice

impaired endothelial cell insulin transcytosis in culture and in vivo. These
effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM
patients was also hyposialylated. In HFD-fed mice, supplementation with the
sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and
preserved insulin sensitivity without affecting weight gain. Thus, IgG
sialylation and endothelial FcγRIIB may represent promising therapeutic targets
to sever the link between obesity and T2DM.
DOI: 10.1172/JCI89333
PMCID: PMC5749535
PMID: 29202472
154. Oxid Med Cell Longev. 2017;2017:5350267. doi: 10.1155/2017/5350267. Epub 2017 May
8.
Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and
Nitrate.
Norouzirad R(1)(2), González-Muniesa P(3)(4)(5)(6), Ghasemi A(1).
Author information:
(1)Endocrine Physiology Research Center, Research Institute for Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
(2)Dezful University of Medical Sciences, Dezful, Iran.
(3)Centre for Nutrition Research, School of Pharmacy and Nutrition, University of
Navarra, Pamplona, Spain.
(4)Department of Nutrition, Food Sciences and Physiology, School of Pharmacy and
Nutrition, University of Navarra, Pamplona, Spain.
(5)IDISNA Navarra's Health Research Institute, Pamplona, Spain.
(6)CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud

Carlos III, Madrid, Spain.
The prevalence of obesity and diabetes is increasing worldwide. Obesity and
diabetes are associated with oxidative stress, inflammation, endothelial
dysfunction, insulin resistance, and glucose intolerance. Obesity, a chronic
hypoxic state that is associated with decreased nitric oxide (NO)
bioavailability, is one of the main causes of type 2 diabetes. The
hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of several
genes of the metabolic pathways including proinflammatory adipokines, endothelial
NO synthase (eNOS), and insulin signaling components. It seems that adipose
tissue hypoxia and NO-dependent vascular and cellular dysfunctions are
responsible for other consequences linked to obesity-related disorders. Although
hyperoxia could reverse hypoxic-related disorders, it increases the production of
reactive oxygen species (ROS) and decreases the production of NO. Nitrate can
restore NO depletion and has antioxidant properties, and recent data support the
beneficial effects of nitrate therapy in obesity and diabetes. Although it seems
reasonable to combine hyperoxia and nitrate treatments for managing
obesity/diabetes, the combined effects have not been investigated yet. This
review discusses some aspects of tissue oxygenation and the potential effects of
hyperoxia and nitrate interventions on obesity/diabetes management. It can be
proposed that concomitant use of hyperoxia and nitrate is justified for managing
obesity and diabetes.
DOI: 10.1155/2017/5350267
PMCID: PMC5457776
155. Front Pharmacol. 2017 Jun 8;8:333. doi: 10.3389/fphar.2017.00333. eCollection
2017.
Amorpha fruticosa - A Noxious Invasive Alien Plant in Europe or a Medicinal Plant
against Metabolic Disease?
Kozuharova E(1), Matkowski A(2), Woźniak D(2), Simeonova R(3), Naychov Z(4),
Malainer C(5), Mocan A(6)(7), Nabavi SM(8), Atanasov AG(9)(10)(11).
Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Medical University of
SofiaSofia, Bulgaria.
(2)Department of Pharmaceutical Biology with Botanical Garden of Medicinal
PlantsMedical University of Wroclaw, Poland.
(3)Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of
Pharmacy, Medical University of SofiaSofia, Bulgaria.
(4)Sofia University St. Kliment Ohridski, Faculty of Medicine, Department of
Surgery, Obstetrics and Gynecology, Division of Cardiac Surgery, University
Hospital LozenetzSofia, Bulgaria.
(5)Independent ResearcherVienna, Austria.
(6)Department of Pharmaceutical Botany, Iuliu Haţieganu University of Medicine
and PharmacyCluj-Napoca, Romania.
(7)ICHAT and Institute for Life Sciences, University of Agricultural Sciences and
Veterinary MedicineCluj-Napoca, Romania.
(8)Applied Biotechnology Research Center, Baqiyatallah University of Medical
SciencesTehran, Iran.
(9)Institute of Genetics and Animal Breeding, Polish Academy of
SciencesJastrzebiec, Poland.
(10)Department of Pharmacognosy, University of ViennaVienna, Austria.
(11)Department of Vascular Biology and Thrombosis Research, Center for Physiology
and Pharmacology, Medical University of ViennaVienna, Austria.
Amorpha fruticosa L. (Fabaceae) is a shrub native to North America which has been
cultivated mainly for its ornamental features, honey plant value and protective
properties against soil erosion. It is registered amongst the most noxious
invasive species in Europe. However, a growing body of scientific literature also
points to the therapeutic potential of its chemical constituents. Due to the fact
that A. fruticosa is an aggressive invasive species, it can provide an abundant
and cheap resource of plant chemical constituents which can be utilized for
therapeutic purposes. Additionally, exploitation of the biomass for medicinal use
might contribute to relieving the destructive impact of this species on natural
habitats. The aim of this review is to provide a comprehensive summary and
systematize the state-of-the-art in the knowledge of the phytochemical
composition and the potential of A. fruticosa in disease treatment and
prevention, with especial emphasis on diabetes and metabolic syndrome. Also
reviewed are aspects related to potential toxicity of A. fruticosa which has not
yet been systematically evaluated in human subjects.
DOI: 10.3389/fphar.2017.00333
PMCID: PMC5462938
PMID: 28642702
156. BMC Health Serv Res. 2018 May 2;18(1):316. doi: 10.1186/s12913-018-3148-0.
Identifying diabetes cases from administrative data: a population-based
validation study.
Lipscombe LL(1)(2)(3)(4), Hwee J(5)(6), Webster L(5), Shah BR(7)(5)(8)(9), Booth
GL(7)(5)(8)(10), Tu K(8)(11)(12).
Author information:
(1)Women's College Research Institute, Women's College Hospital, 76 Grenville
Street, Toronto, ON, M5S 1B1, Canada. Lorraine.Lipscombe@wchospital.ca.
(2)Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth

Street, Toronto, ON, M5G 2C4, Canada. Lorraine.Lipscombe@wchospital.ca.
(3)Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Avenue,
Toronto, ON, M4N 3M5, Canada. Lorraine.Lipscombe@wchospital.ca.
(4)Institute of Health Policy, Management and Evaluation, University of Toronto,
4th Floor, 155 College St, Toronto, ON, M5T 3M6, Canada.
Lorraine.Lipscombe@wchospital.ca.
(5)Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Avenue,
Toronto, ON, M4N 3M5, Canada.
(6)Dalla Lana School of Public Health, University of Toronto, 6th Floor, 155
College St, Toronto, ON, M5T 3M7, Canada.
(7)Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth
Street, Toronto, ON, M5G 2C4, Canada.
(8)Institute of Health Policy, Management and Evaluation, University of Toronto,
4th Floor, 155 College St, Toronto, ON, M5T 3M6, Canada.
(9)Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5,
Canada.
(10)Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond St, Toronto,
ON, M5B 1W8, Canada.
(11)Department of Community and Family Medicine, University of Toronto, 5th
Floor, 500 University Avenue, Toronto, ON, M5G 1V7, Canada.
(12)University Health Network, R. Fraser Elliot Building, 1st Floor, 190
Elizabeth St, Toronto, ON, M5G 2C4, Canada.
BACKGROUND: Health care data allow for the study and surveillance of chronic
diseases such as diabetes. The objective of this study was to identify and
validate optimal algorithms for diabetes cases within health care administrative
databases for different research purposes, populations, and data sources.
METHODS: We linked health care administrative databases from Ontario, Canada to a
reference standard of primary care electronic medical records (EMRs). We then
identified and calculated the performance characteristics of multiple adult
diabetes case definitions, using combinations of data sources and time windows.
RESULTS: The best algorithm to identify diabetes cases was the presence at any
time of one hospitalization or physician claim for diabetes AND either one
prescription for an anti-diabetic medication or one physician claim with a
diabetes-specific fee code [sensitivity 84.2%, specificity 99.2%, positive
predictive value (PPV) 92.5%]. Use of physician claims alone performed almost as
well: three physician claims for diabetes within one year was highly specific
(sensitivity 79.9%, specificity 99.1%, PPV 91.4%) and one physician claim at any
time was highly sensitive (sensitivity 93.6%, specificity 91.9%, PPV 58.5%).
CONCLUSIONS: This study identifies validated algorithms to capture diabetes cases
within health care administrative databases for a range of purposes, populations
and data availability. These findings are useful to study trends and outcomes of
diabetes using routinely-collected health care data.
DOI: 10.1186/s12913-018-3148-0
PMCID: PMC5932874
PMID: 29720153
157. Diabetes Ther. 2017 Dec;8(6):1379-1392. doi: 10.1007/s13300-017-0327-7. Epub 2017
Nov 1.
Identifying Patterns of Lifestyle Behaviors among People with Type 2 Diabetes in
Tianjin, China: A Latent Class Analysis.
Wang X(1), Chen J(1), Liu X(1), Gao F(1), Zhao H(1), Han D(1), Jing X(1), Liu
Y(1), Cui Z(1), Li C(2), Ma J(3).
Author information:
(1)Department of Health Statistics, College of Public Health, Tianjin Medical
University, Heping District, Tianjin, People's Republic of China.

lichangping@tmu.edu.cn.
junma@tmu.edu.cn.
INTRODUCTION: Lifestyle behaviors are essential elements of diabetes care. The
aims of this study were to identify distinct subgroups of people with type 2
diabetes based on personal levels of lifestyle behaviors and explore the
different characteristics across these subgroups.
METHODS: In 2015 and 2016, 1504 outpatients with a diagnosis of type 2 diabetes
were selected via two-stage simple random sampling from 10 municipal district
hospitals in Tianjin. Participants accepted an invitation by experienced
physicians to complete a questionnaire containing demographic and lifestyle
content. Clinical data were collected by reviewing medical records. Latent class
analysis was applied to identify patterns of lifestyle behaviors. Multinomial
logistic regression was used to investigate the characteristics of the subgroups.
RESULTS: The final model yielded a four-class solution: the healthy behavioral
group, unhealthy diet and less activity group, smoking and drinking group, and
sedentary and extremely inactive group. Further analysis found that variables,
including age, sex, general/central obesity, treatment modalities, glycemic
control, diabetes duration, and diabetes-related complications and comorbidities,
were disproportionately distributed across the four latent classes (P < 0.05).
Participants in the unhealthy diet and less activity group were more likely to
have a longer duration of diabetes, poor glycemic control and more
diabetes-related diseases relative to the other three latent classes.
CONCLUSIONS: Identification and characterization of subgroups based on lifestyle
behaviors in individuals with type 2 diabetes can help health care providers to
shift to targeted intervention strategies.
DOI: 10.1007/s13300-017-0327-7
PMCID: PMC5688992
PMID: 29094299
158. Oxid Med Cell Longev. 2018 Aug 14;2018:2378189. doi: 10.1155/2018/2378189.
eCollection 2018.
Impact of Obesity and Hyperglycemia on Placental Mitochondria.
Mandò C(1), Anelli GM(1), Novielli C(1), Panina-Bordignon P(2), Massari M(1),
Mazzocco MI(1), Cetin I(1).
Author information:
(1)Department of Biomedical and Clinical Sciences, Unit of Obstetrics and
Gynecology, ASST Fatebenefratelli Sacco University Hospital, Università degli
Studi di Milano, Via G. B. Grassi 74, 20157 Milano, Italy.
(2)Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Via
Olgettina 60, 20132 Milano, Italy.
A lipotoxic placental environment is recognized in maternal obesity, with
increased inflammation and oxidative stress. These changes might alter
mitochondrial function, with excessive production of reactive oxygen species, in
a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes.
Here, we hypothesize that maternal pregestational body mass index (BMI) and
glycemic levels can alter placental mitochondria. We measured mitochondrial DNA
(mtDNA, real-time PCR) and morphology (electron microscopy) in placentas of
forty-seven singleton pregnancies at elective cesarean section. Thirty-seven
women were normoglycemic: twenty-one normal-weight women, NW, and sixteen obese
women, OB/GDM(-). Ten obese women had gestational diabetes mellitus, OB/GDM(+).
OB/GDM(-) presented higher mtDNA levels versus NW, suggesting increased
mitochondrial biogenesis in the normoglycemic obese group. These mitochondria

showed similar morphology to NW. On the contrary, in OB/GDM(+), mtDNA was not
significantly increased versus NW. Nevertheless, mitochondria showed
morphological abnormalities, indicating impaired functionality. The metabolic
response of the placenta to impairment in obese pregnancies can possibly vary
depending on several parameters, resulting in opposite strains acting when
insulin resistance of GDM occurs in the obese environment, characterized by
inflammation and oxidative stress. Therefore, mitochondrial alterations represent
a feature of obese pregnancies with changes in placental energetics that possibly
can affect pregnancy outcomes.
DOI: 10.1155/2018/2378189
PMCID: PMC6112210
PMID: 30186542
159. Sci Rep. 2018 May 25;8(1):8149. doi: 10.1038/s41598-018-25092-6.
Impact of rural-urban environment on metabolic profile and response to a 5-day
high-fat diet.
Tahapary DL(1)(2)(3)(4), de Ruiter K(5), Kurniawan F(6)(7), Djuardi Y(8)(9), Wang
Y(10), Nurdin SME(11), Iskandar E(8)(9), Minggu D(12), Yunir E(6)(7), Guigas
B(5), Supali T(8)(9), Rensen PCN(10), Sartono E(5), Soewondo P(6)(7), Harbuwono
DS(6)(7), Smit JWA(7)(13), Yazdanbakhsh M(14).
Author information:
(1)Department of Internal Medicine, Division of Endocrinology, Dr. Cipto
Mangunkusumo National General Hospital, Faculty of Medicine Universitas
Indonesia, Jakarta, Indonesia. dicky.tahapary@ui.ac.id.
(2)Department of Parasitology, Leiden University Medical Center, Leiden, The
Netherlands. dicky.tahapary@ui.ac.id.
(3)Nangapanda Community Research Cluster, The Indonesian Medical Education and
Research Institute, Universitas Indonesia, Jakarta, Indonesia.
dicky.tahapary@ui.ac.id.
(4)Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical
Education and Research Institute, Universitas Indonesia, Jakarta, Indonesia.
dicky.tahapary@ui.ac.id.
Netherlands.
(6)Department of Internal Medicine, Division of Endocrinology, Dr. Cipto
Mangunkusumo National General Hospital, Faculty of Medicine Universitas
Indonesia, Jakarta, Indonesia.
(7)Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical
Education and Research Institute, Universitas Indonesia, Jakarta, Indonesia.
(8)Nangapanda Community Research Cluster, The Indonesian Medical Education and
Research Institute, Universitas Indonesia, Jakarta, Indonesia.
(9)Department of Parasitology, Faculty of Medicine Universitas Indonesia,
Jakarta, Indonesia.
(10)Department of Medicine, Division of Endocrinology, Leiden University Medical
Center, Leiden, The Netherlands.
(11)Laboratory Unit, South East Asian Minister of Education Organization Regional
Centre For Food And Nutrition, Jakarta, Indonesia.
(12)Dr. W.Z. Johannes Hospital, Kupang, Indonesia.
(13)Department of Internal Medicine, Radboud University Medical Centre, Nijmegen,
The Netherlands.
Netherlands. m.yazdanbakhsh@lumc.nl.
Epidemiological studies have indicated that rural living might be protective
against type 2 diabetes development. We compared the metabolic profile and
response to a short-term high-fat high-calorie diet (HFD) of men with the same
genetic background living in an urban and rural area of Indonesia. First, we

recruited 154 Floresian male subjects (18-65 years old), of whom 105 lived in a
rural area (Flores) and 49 had migrated and lived in urban area (Jakarta) for
more than 1 year. The urban group had significantly higher whole-body insulin
resistance (IR), as assessed by homeostatic-model-assessment of IR (HOMA-IR),
[mean difference (95% CI), p-value: 0.10 (0.02-0.17), p = 0.01]. Next, we
recruited 17 urban and 17 rural age-and-BMI-matched healthy-young-male volunteers
for a 5-day HFD challenge. The HOMA-IR increased in both groups similarly -0.77
(-2.03-0.49), p = 0.22]. Neither rural living nor factors associated with rural
living, such as current helminth infection or total IgE, were associated with
protection against acute induction of IR by HFD.
DOI: 10.1038/s41598-018-25092-6
PMCID: PMC5970191
PMID: 29802315
160. Diab Vasc Dis Res. 2018 Jul;15(4):302-313. doi: 10.1177/1479164118759220. Epub
2018 Mar 2.
In vivo inhibition of nuclear factor of activated T-cells leads to
atherosclerotic plaque regression in IGF-II/LDLR-/-ApoB100/100 mice.
Blanco F(1)(2), Heinonen SE(3), Gurzeler E(4), Berglund LM(1), Dutius Andersson
AM(1), Kotova O(1), Jönsson-Rylander AC(3), Ylä-Herttuala S(4)(5), Gomez MF(1).
Author information:
(1)1 Department of Clinical Sciences, Malmö, Lund University Diabetes Centre
(LUDC), Lund University, Malmö, Sweden.
(2)2 Departamento de Biofísica, Facultad de Medicina, Universidad de la
República, Montevideo, Uruguay.
(3)3 Bioscience, Cardiovascular, Renal and Metabolic diseases, Innovative

Medicines and Early Development Biotech Unit, AstraZeneca Gothenburg, Sweden.
(4)4 A.I. Virtanen Institute for Molecular Sciences, University of Eastern
Finland, Kuopio, Finland.
(5)5 Heart Center, Kuopio University Hospital, Kuopio, Finland.
AIMS: Despite vast clinical experience linking diabetes and atherosclerosis, the
molecular mechanisms leading to accelerated vascular damage are still unclear.
Here, we investigated the effects of nuclear factor of activated T-cells
inhibition on plaque burden in a novel mouse model of type 2 diabetes that better
replicates human disease.
METHODS & RESULTS: IGF-II/LDLR-/-ApoB100/100 mice were generated by crossbreeding
low-density lipoprotein receptor-deficient mice that synthesize only
apolipoprotein B100 (LDLR-/-ApoB100/100) with transgenic mice overexpressing
insulin-like growth factor-II in pancreatic β cells. Mice have mild
hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions.
In vivo treatment with the nuclear factor of activated T-cells blocker A-285222
for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the
brachiocephalic artery of IGF-II/LDLR-/-ApoB100/100 mice, as assessed
non-invasively using ultrasound biomicroscopy prior and after treatment, and
histologically after termination. Treatment had no impact on plaque composition
(i.e. muscle, collagen, macrophages). The reduced plaque area could not be
explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition
of nuclear factor of activated T-cells was associated with increased expression
of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic
vascular smooth muscle cells.
CONCLUSION: Targeting the nuclear factor of activated T-cells signalling pathway
may be an attractive approach for the treatment of diabetic macrovascular
complications.
DOI: 10.1177/1479164118759220
PMCID: PMC6039864
161. Am J Physiol Endocrinol Metab. 2017 Oct 1;313(4):E450-E462. doi:
10.1152/ajpendo.00093.2017. Epub 2017 Jun 27.
Increased adipose tissue aromatase activity improves insulin sensitivity and
reduces adipose tissue inflammation in male mice.
Ohlsson C(1), Hammarstedt A(2), Vandenput L(1), Saarinen N(3), Ryberg H(1),
Windahl SH(1), Farman HH(1), Jansson JO(4), Movérare-Skrtic S(1), Smith U(2),
Zhang FP(3), Poutanen M(3), Hedjazifar S(2), Sjögren K(5).
Author information:
(1)Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden.
(2)Lundberg Laboratory for Diabetes Research, Department of Molecular and
Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg,
Sweden.
(3)University of Turku, Institute of Biomedicine, Turku Center for Disease
Modeling, Department of Physiology, Turku, Finland; and.
(4)Institute of Neuroscience and Physiology/Endocrinology, Sahlgrenska Academy,
University of Gothenburg, Gothenburg, Sweden.
(5)Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden; Klara.Sjogren@medic.gu.se.
Females are, in general, more insulin sensitive than males. To investigate
whether this is a direct effect of sex-steroids (SS) in white adipose tissue
(WAT), we developed a male mouse model overexpressing the aromatase enzyme,
converting testosterone (T) to estradiol (E2), specifically in WAT (Ap2-arom
mice). Adipose tissue E2 levels were increased while circulating SS levels were
unaffected in male Ap2-arom mice. Importantly, male Ap2-arom mice were more
insulin sensitive compared with WT mice and exhibited increased serum adiponectin
levels and upregulated expression of Glut4 and Irs1 in WAT. The expression of
markers of macrophages and immune cell infiltration was markedly decreased in WAT
of male Ap2-arom mice. The adipogenesis was enhanced in male Ap2-arom mice,
supported by elevated Pparg expression in WAT and enhanced differentiation of
preadipocyte into mature adipocytes. In summary, increased adipose tissue
aromatase activity reduces adipose tissue inflammation and improves insulin
sensitivity in male mice. We propose that estrogen increases insulin sensitivity
via a local effect in WAT on adiponectin expression, adipose tissue inflammation,
and adipogenesis.
Copyright © 2017 the American Physiological Society.
DOI: 10.1152/ajpendo.00093.2017
PMCID: PMC5668598
162. J Diabetes. 2017 Oct;9(10):898-907. doi: 10.1111/1753-0407.12510. Epub 2017 Jan
20.
Increased identification of novel variants in type 2 diabetes, birth weight and
their pleiotropic loci.
Zeng CP(1)(2), Chen YC(1), Lin X(1), Greenbaum J(3), Chen YP(2), Peng C(1), Wang
XF(1), Zhou R(1), Deng WM(4), Shen J(1), Deng HW(1)(3).
Author information:
(1)Department of Endocrinology and Metabolism, The Third Affiliated Hospital of
Southern Medical University, Guangzhou, China.

(2)Department of Endocrinology and Metabolism, Affiliated Nanhai Hospital of
Southern Medical University, Guangzhou, China.
(3)Department of Biostatistics and Bioinformatics, Center for Bioinformatics and
Genomics, Tulane University, New Orleans, Louisiana, USA.
(4)Department of Rehabilitation, General Hospital of Guangzhou Military Command
of Chinese PLA, Guangzhou, China.
BACKGROUND: Clinical and epidemiological findings point to an association between
type 2 diabetes (T2D) and low birth weight. However, the nature of the
relationship is largely unknown. The aim of this study was to identify novel
single nucleotide polymorphisms (SNPs) in T2D and birth weight, and their
pleiotropic loci.
METHODS: A pleiotropy-informed conditional false discovery rate (cFDR) method was
applied to two independent genome-wide association studies (GWAS) summary
statistics of T2D (n = 149 821) and birth weight (n = 26 836).
RESULTS: A conditional Q-Q plot showed strong enrichment of genetic variants in
T2D conditioned on different levels of association with birth weight. 133
T2D-associated SNPs, including 120 novel SNPs, were identified with a
significance threshold of cFDR < 0.05; 13 significant birth weight-associated
SNPs, including 12 novel SNPs (cFDR < 0.05) were identified. Conjunctional cFDR
(ccFDR) analysis identified nine pleiotropic loci, including seven novel loci,
shared by both T2D and birth weight (ccFDR < 0.05). Two novel SNPs located at the
CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1; rs1012635; cFDR <
0.05) and adenylate cyclase 5 (ADCY5; rs4677887; cFDR < 0.05) genes are of note.
These two genes increase the risk of T2D and low birth weight through the pathway
of the "fetal insulin hypothesis."
CONCLUSION: Several pleiotropic loci were identified between T2D and birth weight
by leveraging GWAS results. The results make it possible to explain a greater
proportion of trait heritability and improve our understanding of the shared
pathophysiology between T2D and birth weight.

© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John
Wiley & Sons Australia, Ltd.
DOI: 10.1111/1753-0407.12510
PMCID: PMC5841537
163. BMJ Open. 2018 Apr 10;8(4):e019675. doi: 10.1136/bmjopen-2017-019675.
IndEcho study: cohort study investigating birth size, childhood growth and young
adult cardiovascular risk factors as predictors of midlife myocardial structure
and function in South Asians.
Vasan SK(1)(2), Roy A(3)(4), Samuel VT(5), Antonisamy B(5), Bhargava SK(6), Alex
AG(5), Singh B(6), Osmond C(1), Geethanjali FS(5), Karpe F(2), Sachdev H(7),
Agrawal K(5), Ramakrishnan L(4), Tandon N(4), Thomas N(5), Premkumar PS(5),
Asaithambi P(5), Princy SFX(5), Sinha S(7), Paul TV(5), Prabhakaran D(3)(8), Fall
CHD(1).
Author information:
(1)MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton
General Hospital, Southampton, UK.
(2)Oxford Center for Diabetes, Endocrinology and Metabolism, Radcliffe Department
of Medicine, University of Oxford, Oxford, UK.
(3)Centre for Chronic Disease Control, New Delhi, India.
(4)Department of Cardiology, All-India Institute of Medical Sciences, New Delhi,
India.
(5)Departments of Cardiology, Biostatistics, Endocrinology and Clinical
Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India.
(6)Department of Paediatrics, Sunder Lal Jain Hospital, New Delhi, India.

(7)Department of Paediatrics, Sitaram Bhartia Institute of Science and Research,
New Delhi, India.
(8)Public Health Foundation of India, New Delhi, India.
INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and
its risk factors (hypertension, diabetes, dyslipidaemia and central obesity).
Left ventricular (LV) hypertrophy and dysfunction are features of these disorders
and important predictors of CVD mortality. Lower birth and infant weight and
greater childhood weight gain are associated with increased adult CVD mortality,
but there are few data on their relationship to LV function. The IndEcho study
will examine associations of birth size, growth during infancy, childhood and
adolescence and CVD risk factors in young adulthood with midlife cardiac
structure and function in South Asian Indians.
METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged
43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth
Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements
of weight and height from birth to early adulthood. CVD risk markers (body
composition, blood pressure, glucose tolerance and lipids) and lifestyle
characteristics (tobacco and alcohol consumption, physical activity,
socioeconomic status) were assessed at age ~30 years. Clinical measurements in
IndEcho will include anthropometry, blood pressure, biochemistry (glucose,
fasting insulin and lipids, urinary albumin/creatinine ratio) and body
composition by dual energy X-ray absorptiometry and bioelectrical impedance.
Outcomes are LV mass and indices of LV systolic and diastolic function assessed
by two-dimensional and Doppler echocardiography, carotid intimal-media thickness
and ECG indicators of ischaemia. Regression and conditional growth models,
adjusted for potential confounders, will be used to study associations of
childhood and young adult exposures with these cardiovascular outcomes.
ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry
Steering Committee, Government of India and institutional ethics committees of
participating centres in India and the University of Southampton, UK. Results

will be disseminated through scientific meetings and peer-reviewed journals.
TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results.
© Article author(s) (or their employer(s) unless otherwise stated in the text of
the article) 2018. All rights reserved. No commercial use is permitted unless
otherwise expressly granted.
DOI: 10.1136/bmjopen-2017-019675
PMCID: PMC5898335
PMID: 29643156
164. Diabetes Care. 2018 Jun;41(6):1268-1274. doi: 10.2337/dc17-2046. Epub 2018 Apr 4.
Influence of Diabetes on Trends in Perioperative Cardiovascular Events.
Newman JD(1), Wilcox T(2), Smilowitz NR(2), Berger JS(2).
Author information:
(1)Division of Cardiology, Department of Medicine, New York University School of
Medicine, New York, NY jonathan.newman@nyumc.org.
(2)Division of Cardiology, Department of Medicine, New York University School of
Medicine, New York, NY.
OBJECTIVE: Patients undergoing noncardiac surgery frequently have diabetes
mellitus (DM) and an elevated risk of cardiovascular disease. It is unknown
whether temporal declines in the frequency of perioperative major adverse
cardiovascular and cerebrovascular events (MACCEs) apply to patients with DM.
RESEARCH DESIGN AND METHODS: Patients ≥45 years of age who underwent noncardiac
surgery from January 2004 to December 2013 were identified using the U.S.
National Inpatient Sample. DM was identified using ICD-9 diagnosis codes.
Perioperative MACCEs (in-hospital all-cause mortality, acute myocardial
infarction, or acute ischemic stroke) by DM status were evaluated over time.
RESULTS: The final study sample consisted of 10,581,621 hospitalizations for
major noncardiac surgery; DM was present in ∼23% of surgeries and increased over
time (P for trend <0.001). Patients with DM experienced MACCEs in 3.3% of
surgeries vs. 2.8% of surgeries for patients without DM (P < 0.001). From 2004 to
2013, the odds of perioperative MACCEs after multivariable adjustment increased
by 6% (95% CI 2-9) for DM patients, compared with an 8% decrease (95% CI -10 to
-6) for patients without DM (P for interaction <0.001). Trends for individual end
points were all less favorable for patients with DM versus those without DM.
CONCLUSIONS: In an analysis of >10.5 million noncardiac surgeries from a large
U.S. hospital admission database, perioperative MACCEs were more common among
patients with DM versus those without DM. Perioperative MACCEs increased over
time and individual end points were all less favorable for patients with DM. Our
findings suggest that a substantial unmet need exists for strategies to reduce
the risk of perioperative cardiovascular events among patients with DM.
DOI: 10.2337/dc17-2046
165. J Am Coll Cardiol. 2018 Jun 26;71(25):2867-2876. doi: 10.1016/j.jacc.2018.04.027.
Influence of Lifestyle on Incident Cardiovascular Disease and Mortality in
Patients With Diabetes Mellitus.

Liu G(1), Li Y(1), Hu Y(1), Zong G(2), Li S(3), Rimm EB(4), Hu FB(4), Manson
JE(5), Rexrode KM(6), Shin HJ(7), Sun Q(8).
Author information:
(1)Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston,
Massachusetts.
(2)Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai, China.
(3)Boston University School of Medicine, Clinical Epidemiology Unit, Boston,
Massachusetts.
Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public
Health, Boston, Massachusetts; Channing Division of Network Medicine, Department
of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston,
Massachusetts.
(5)Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston,
Massachusetts; Channing Division of Network Medicine, Department of Medicine,
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts.
(6)Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts; Division of Women's
Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical
School, Boston, Massachusetts.
(7)Department of Medicine, Brigham and Women's Hospital, Veterans Affairs Boston
Healthcare System, Harvard Medical School, Boston, Massachusetts.
Massachusetts; Channing Division of Network Medicine, Department of Medicine,
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Electronic address: qisun@hsph.harvard.edu.

BACKGROUND: Evidence is limited regarding the impact of healthy lifestyle
practices on the risk of subsequent cardiovascular events among patients with
diabetes.
OBJECTIVES: The purpose of this study was to examine the associations of an
overall healthy lifestyle, defined by eating a high-quality diet (top two-fifths
of Alternative Healthy Eating Index), nonsmoking, engaging in moderate- to
vigorous-intensity physical activity (≥150 min/week), and drinking alcohol in
moderation (5 to 15 g/day for women and 5 to 30 g/day for men), with the risk of
developing cardiovascular disease (CVD) and CVD mortality among adults with type
2 diabetes (T2D).
METHODS: This prospective analysis included 11,527 participants with T2D
diagnosed during follow-up (8,970 women from the Nurses' Health Study and 2,557
men from the Health Professionals Follow-Up Study), who were free of CVD and
cancer at the time of diabetes diagnosis. Diet and lifestyle factors before and
after T2D diagnosis were repeatedly assessed every 2 to 4 years.
RESULTS: There were 2,311 incident CVD cases and 858 CVD deaths during an average
of 13.3 years of follow-up. After multivariate adjustment of covariates, the
low-risk lifestyle factors after diabetes diagnosis were each associated with a
lower risk of CVD incidence and CVD mortality. The multivariate-adjusted hazard
ratios for participants with 3 or more low-risk lifestyle factors compared with 0
were 0.48 (95% confidence interval [CI]: 0.40 to 0.59) for total CVD incidence,
0.53 (95% CI: 0.42 to 0.66) for incidence of coronary heart disease, 0.33 (95%
CI: 0.21 to 0.51) for stroke incidence, and 0.32 (95% CI: 0.22 to 0.47) for CVD
mortality (all p trend <0.001). The population-attributable risk for poor
adherence to the overall healthy lifestyle (<3 low-risk factors) was 40.9% (95%
CI: 28.5% to 52.0%) for CVD mortality. In addition, greater improvements in
healthy lifestyle factors from pre-diabetes to post-diabetes diagnosis were also
significantly associated with a lower risk of CVD incidence and CVD mortality.
For each number increment in low-risk lifestyle factors there was a 14% lower
risk of incident total CVD, a 12% lower risk of coronary heart disease, a 21%
lower risk of stroke, and a 27% lower risk of CVD mortality (all p < 0.001).
Similar results were observed when analyses were stratified by diabetes duration,
sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle
factors before diabetes diagnosis.
CONCLUSIONS: Greater adherence to an overall healthy lifestyle is associated with
a substantially lower risk of CVD incidence and CVD mortality among adults with
T2D. These findings further support the tremendous benefits of adopting a healthy
lifestyle in reducing the subsequent burden of cardiovascular complications in
patients with T2D.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier
Inc. All rights reserved.
DOI: 10.1016/j.jacc.2018.04.027
PMID: 29929608
166. Molecules. 2018 Oct 11;23(10). pii: E2605. doi: 10.3390/molecules23102605.
Insulin Mimetic Properties of Extracts Prepared from Bellis perennis.
Haselgrübler R(1), Stadlbauer V(2)(3), Stübl F(4), Schwarzinger B(5)(6),
Rudzionyte I(7), Himmelsbach M(8), Iken M(9), Weghuber J(10)(11).
Author information:
(1)School of Engineering, University of Applied Sciences Upper Austria,
Stelzhamerstrasse 23, A-4600 Wels, Austria. renate.haselgruebler@fh-wels.at.
Stelzhamerstrasse 23, A-4600 Wels, Austria. verena.stadlbauer@fh-wels.at.
(3)Austrian Competence Center for Feed and Food Quality, Safety and Innovation,
A-4600 Wels, Austria. verena.stadlbauer@fh-wels.at.

Stelzhamerstrasse 23, A-4600 Wels, Austria. flora.stuebl@fh-wels.at.
Stelzhamerstrasse 23, A-4600 Wels, Austria. bettina.schwarzinger@fh-wels.at.
A-4600 Wels, Austria. bettina.schwarzinger@fh-wels.at.
Stelzhamerstrasse 23, A-4600 Wels, Austria. ieva.rudzionyte@fh-wels.at.
(8)Institute for Analytical Chemistry, Johannes Kepler University, A-4040 Linz,
Austria. markus.himmelsbach@jku.at.
(9)PM International AG, L-5445 Schengen, Luxembourg.
marcus.iken@pm-international.de.
Stelzhamerstrasse 23, A-4600 Wels, Austria. julian.weghuber@fh-wels.at.
A-4600 Wels, Austria. julian.weghuber@fh-wels.at.
Diabetes mellitus (DM) and consequential cardiovascular diseases lead to millions
of deaths worldwide each year; 90% of all people suffering from DM are classified
as Type 2 DM (T2DM) patients. T2DM is linked to insulin resistance and a loss of
insulin sensitivity. It leads to a reduced uptake of glucose mediated by glucose
transporter 4 (GLUT4) in muscle and adipose tissue, and finally hyperglycemia.
Using a fluorescence microscopy-based screening assay we searched for herbal
extracts that induce GLUT4 translocation in the absence of insulin, and confirmed
their activity in chick embryos. We found that extracts prepared from Bellis
perennis (common daisy) are efficient inducers of GLUT4 translocation in the
applied in vitro cell system. In addition, these extracts also led to reduced
blood glucose levels in chicken embryos (in ovo), confirming their activity in a
living organism. Using high-performance liquid chromtaography (HPLC) analysis, we
identified and quantified numerous polyphenolic compounds including apigenin
glycosides, quercitrin and chlorogenic acid, which potentially contribute to the

induction of GLUT4 translocation. In conclusion, Bellis perennis extracts reduce
blood glucose levels and are therefore suitable candidates for application in
food supplements for the prevention and accompanying therapy of T2DM.
DOI: 10.3390/molecules23102605
PMCID: PMC6222741
PMID: 30314325
167. Front Endocrinol (Lausanne). 2018 Sep 5;9:514. doi: 10.3389/fendo.2018.00514.
eCollection 2018.
Insulin Resistance in HIV-Patients: Causes and Consequences.
Pedro MN(1), Rocha GZ(1), Guadagnini D(1), Santos A(1), Magro DO(2), Assalin
HB(1), Oliveira AG(1)(3), Pedro RJ(1), Saad MJA(1).
Author information:
(1)Department of Internal Medicine, Faculty of Medical Sciences, State University
of Campinas-UNICAMP, Campinas, Brazil.
(2)Department of Surgery, Faculty of Medical Sciences, State University of
Campinas-UNICAMP, Campinas, Brazil.
(3)Biosciences Institute, São Paulo State University (UNESP), Rio Claro, Brazil.
Here we review how immune activation and insulin resistance contribute to the
metabolic alterations observed in HIV-infected patients, and how these
alterations increase the risk of developing CVD. The introduction and evolution
of antiretroviral drugs over the past 25 years has completely changed the
clinical prognosis of HIV-infected patients. The deaths of these individuals are
now related to atherosclerotic CVDs, rather than from the viral infection itself.
However, HIV infection, cART, and intestinal microbiota are associated with
immune activation and insulin resistance, which can lead to the development of a
variety of diseases and disorders, especially with regards to CVDs. The increase
in LPS and proinflammatory cytokines circulating levels and intracellular
mechanisms activate serine kinases, resulting in insulin receptor substrate-1
(IRS-1) serine phosphorylation and consequently a down regulation in insulin
signaling. While lifestyle modifications and pharmaceutical interventions can be
employed to treat these altered metabolic functions, the mechanisms involved in
the development of these chronic complications remain largely unresolved. The
elucidation and understanding of these mechanisms will give rise to new classes
of drugs that will further improve the quality of life of HIV-infected patients,
over the age of 50.
DOI: 10.3389/fendo.2018.00514
PMCID: PMC6133958
PMID: 30233499
168. Am J Clin Nutr. 2017 Jul;106(1):263-275. doi: 10.3945/ajcn.116.150094. Epub 2017
Jun 7.
Interaction between genes and macronutrient intake on the risk of developing type
2 diabetes: systematic review and findings from European Prospective
Investigation into Cancer (EPIC)-InterAct.
Li SX(1), Imamura F(1), Ye Z(1), Schulze MB(2)(3), Zheng J(1), Ardanaz E(4)(5),
Arriola L(5)(6)(7), Boeing H(2), Dow C(8)(9), Fagherazzi G(8)(9), Franks
PW(10)(11), Agudo A(12), Grioni S(13), Kaaks R(14), Katzke VA(14), Key TJ(15),
Khaw KT(16), Mancini FR(8)(9), Navarro C(5)(17)(18), Nilsson PM(10), Onland-Moret
NC(19), Overvad K(20)(21), Palli D(22), Panico S(23), Quirós JR(24), Rolandsson
O(11), Sacerdote C(25)(26)(27), Sánchez MJ(5)(28)(29), Slimani N(30), Sluijs
I(19), Spijkerman AM(31), Tjonneland A(32), Tumino R(33), Sharp SJ(1), Riboli
E(34), Langenberg C(1), Scott RA(1), Forouhi NG(35), Wareham NJ(1).
Author information:
(1)Medical Research Council (MRC) Epidemiology Unit, University of Cambridge,
(2)Department of Molecular Epidemiology, German Institute of Human Nutrition
Potsdam-Rehbruecke, Nuthetal, Germany.
(3)German Center for Diabetes Research (DZD), Düsseldorf, Germany.
(4)Navarre Public Health Institute (ISPN), Pamplona, Spain.
(5)Center for Biomedical Research in Network Epidemiology and Public Health
(CIBERESP), Madrid, Spain.
(6)Public Health Division of Gipuzkoa, San Sebastian, Spain.
(7)Bio-Donostia Institute, Basque Government, San Sebastian, Spain.
(8)French National Institute of Health and Medical Research (INSERM) U1018,
Institut Gustave Roussy, Center for Research in Epidemiology and Population
Health (CESP), Villejuif, France.
(9)University Paris-Saclay, University Paris-Sud, Villejuif, France.
(10)Lund University, Malmö, Sweden.
(11)Umeå University, Umeå, Sweden.
(12)Catalan Institute of Oncology (ICO), Barcelona, Spain.
(13)Epidemiology and Prevention Unit, Milan, Italy.
(14)Division of Cancer Epidemiology, German Cancer Research Center (DKFZ),
Heidelberg, Germany.
(15)University of Oxford, Oxford, United Kingdom.
(16)Department of Public Health and Primary Care, University of Cambridge,
(17)Department of Epidemiology, Murcia Regional Health Council, Biomedical
Research Institute of Murcia (IMIB)-Arrixaca, Murcia, Spain.
(18)Unit of Preventive Medicine and Public Health, School of Medicine, University
of Murcia, Murcia, Spain.
(19)University Medical Center Utrecht, Utrecht, Netherlands.

(20)Section for Epidemiology, Department of Public Health, Aarhus University,
Aarhus, Denmark.
(21)Aalborg University Hospital, Aalborg, Denmark.
(22)Cancer Research and Prevention Institute (ISPO), Florence, Italy.
(23)Department of Clinical Medicine and Surgery, Federico II University, Naples,
Italy.
(24)Public Health Directorate, Asturias, Spain.
(25)Unit of Cancer Epidemiology, City of Health and Science Hospital, University
of Turin, Torino, Italy.
(26)Center for Cancer Prevention (CPO), Torino, Italy.
(27)Human Genetics Foundation (HuGeF), Torino, Italy.
(28)Andalusian School of Public Health, Granada, Spain.
(29)Biosanitary Research Institute of Granada (Granada.ibs), Granada, Spain.
(30)International Agency for Research on Cancer, Lyon, France.
(31)National Institute for Public Health and the Environment (RIVM), Bilthoven,
Netherlands.
(32)Danish Cancer Society Research Center, Copenhagen, Denmark.
(33)Provincial Healthcare Company (ASP) Ragusa, Vittoria, Italy; and.
(34)School of Public Health, Imperial College London, London, United Kingdom.
(35)Medical Research Council (MRC) Epidemiology Unit, University of Cambridge,
Cambridge, United Kingdom; nita.forouhi@mrc-epid.cam.ac.uk.
Background: Gene-diet interactions have been reported to contribute to the
development of type 2 diabetes (T2D). However, to our knowledge, few examples
have been consistently replicated to date.Objective: We aimed to identify
existing evidence for gene-macronutrient interactions and T2D and to examine the
reported interactions in a large-scale study.Design: We systematically reviewed
studies reporting gene-macronutrient interactions and T2D. We searched the
MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials
Registry Platform electronic databases to identify studies published up to
October 2015. Eligibility criteria included assessment of macronutrient quantity

(e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use
of self-report or objective biomarkers of intake. Interactions identified in the
review were subsequently examined in the EPIC (European Prospective Investigation
into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8
European countries). Prentice-weighted Cox regression was used to estimate
country-specific HRs, 95% CIs, and P-interaction values, which were then pooled
by random-effects meta-analysis. A primary model was fitted by using the same
covariates as reported in the published studies, and a second model adjusted for
additional covariates and estimated the effects of isocaloric macronutrient
substitution.Results: Thirteen observational studies met the eligibility criteria
(n < 1700 cases). Eight unique interactions were reported to be significant
between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and
glycemic load derived from self-report of dietary intake and circulating n-3
(ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription
factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR),
caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05). We found no
evidence of interaction when we tried to replicate previously reported
interactions. In addition, no interactions were detected in models with
additional covariates.Conclusions: Eight gene-macronutrient interactions were
identified for the risk of T2D from the literature. These interactions were not
replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in
the original reports. Our findings highlight the importance of independent
replication of reported interactions.
DOI: 10.3945/ajcn.116.150094
PMCID: PMC5486199
169. Clin Interv Aging. 2017 Mar 16;12:535-541. doi: 10.2147/CIA.S126207. eCollection
2017.
Is diabetes mellitus associated with clinical outcomes in aging males treated
with transurethral resection of prostate for bladder outlet obstruction:
implications from Taiwan Nationwide Population-Based Cohort Study.
Lin YH(1), Hou CP(2), Chen TH(3), Juang HH(4), Chang PL(2), Yang PS(2), Lin
YS(5), Chen CL(2), Tsui KH(2).
Author information:
(1)Department of Urology, Chang Gung Memorial Hospital - Linkou; School of
Medicine; Graduate Institute of Clinical Medical Sciences, College of Medicine,
Chang Gung University.
(2)Department of Urology, Chang Gung Memorial Hospital - Linkou; School of
Medicine.
(3)School of Medicine; Division of Cardiology, Department of Internal Medicine,
Chang Gung Memorial Hospital, Keelung.
(4)Department of Anatomy, School of Medicine, Chang Gung University, Kwei-shan,
Tao-Yuan.
(5)School of Medicine; Division of Cardiology, Department of Internal Medicine,
Chang Gung Memorial Hospital, Chiayi, Taiwan, Republic of China.
PURPOSE: We assessed the lower urinary tract symptoms (LUTSs) and clinical
outcomes between diabetes mellitus (DM) patients and non-diabetic (non-DM)
patients receiving transurethral resection of prostate (TUR-P).
METHODS: This analysis was a retrospective cohort study using 13 years
(2000-2012) of claims data from Taiwan's National Health Insurance Research
Database (NHIRD). A total of 4,887 patients who had persistent LUTSs and
underwent TUR-P for prostate enlargement (benign prostate enlargement [BPE]) were
enrolled and divided into two groups: DM and non-DM groups. The patients'
characteristics, postoperative clinical outcomes, and the medication records
after TUR-P were compared. Chi-square test was used for categorical variables and
independent samples t-test for continuous variables. Multivariable logistic
regression analysis was used to compare the risk of postoperative outcomes.
Finally, we estimated the medication-free survival rate after TUR-P using
Kaplan-Meier method and compared it between study groups using log-rank test.
RESULTS: DM group patients had a higher prevalence of comorbidities.
Postoperatively, the DM group had lower rates of urinary tract infection (UTI;
odds ratio [OR], 0.78; P=0.009) and higher rates of urinary retention requiring
catheterization (OR, 1.35; P=0.01) within 1 month after TUR-P. A higher
proportion of patients with DM took anti-muscarinics (OR, 1.23; P=0.032) within
the first 3 months and α-blockers (OR, 1.18; P=0.049) during 3-12 months after
receiving TUR-P. Overall, the DM group patients had a worse postoperative
medication-free survival compared to that of non-DM group patients (95%
confidence interval [95% CI], 1.14; P=0.005).
CONCLUSION: DM patients require higher rates of continuing medication after
TUR-P, especially anti-muscarinics in 3 months postoperatively and alpha-blocker
after 3 months postoperatively. DM patients also had higher incidence of urine
retention after surgery. DM patients had relatively poor treatment outcomes
compared to DM-free patients.
DOI: 10.2147/CIA.S126207
PMCID: PMC5360412
170. Biomed Res Int. 2018 Mar 22;2018:4507659. doi: 10.1155/2018/4507659. eCollection
2018.
JAZF1 Inhibits Adipose Tissue Macrophages and Adipose Tissue Inflammation in

Diet-Induced Diabetic Mice.
Meng F(1), Lin Y(1), Yang M(1), Li M(1), Yang G(2), Hao P(3), Li L(1).
Author information:
(1)The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of
Education and Department of Clinical Biochemistry, College of Laboratory
Medicine, Chongqing Medical University, Chongqing 400010, China.
(2)Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical
University, Chongqing 400010, China.
(3)Department of Laboratory Medicine, Chongqing Three Gorges Medical College,
Chongqing 400020, China.
Background: Juxtaposed with another zinc finger gene 1 (JAZF1) affects
gluconeogenesis, insulin sensitivity, lipid metabolism, and inflammation, but its
exact role in chronic inflammation remains unclear. This study aimed to examine
JAZF1 overexpression in vivo on adipose tissue macrophages (ATMs).
Methods: Mouse models of high-fat diet- (HFD-) induced insulin resistance were
induced using C57BL/6J and JAZF1-overexpressing (JAZF1-OX) mice. The mice were
randomized (8-10/group) to C57BL/6J mice fed regular diet (RD) (NC group),
C57BL/6J mice fed HFD (HF group), JAZF1-OX mice fed RD (NJ group), and JAZF1-OX
mice fed HFD (HJ group). Adipose tissue was harvested 12 weeks later. ATMs were
evaluated by flow cytometry. Inflammatory markers were evaluated by ELISA.
Results: JAZF1-OX mice had lower blood lipids, blood glucose, body weight, fat
weight, and inflammatory markers compared with HF mice (all P < 0.05). JAZF1
overexpression decreased ATM number and secretion of proinflammatory cytokines.
JAZF1 overexpression decreased total CD4+ T cells, active T cells, and memory T
cells and increased Treg cells. JAZF1 overexpression downregulated IFN-γ and
IL-17 levels and upregulated IL-4 levels. JAZF1 overexpression decreased MHCII,
CD40, and CD86 in total ATM, CD11c+ ATM, and CD206+ ATM.
Conclusions: JAZF1 limits adipose tissue inflammation by limiting macrophage

populations and restricting their antigen presentation function.
DOI: 10.1155/2018/4507659
PMCID: PMC5885486
171. Lancet Diabetes Endocrinol. 2017 Mar;5(3):196-213. doi:
10.1016/S2213-8587(17)30015-3. Epub 2017 Jan 24.
Laboratory-based and office-based risk scores and charts to predict 10-year risk
of cardiovascular disease in 182 countries: a pooled analysis of prospective
cohorts and health surveys.
Ueda P(1), Woodward M(2), Lu Y(3), Hajifathalian K(4), Al-Wotayan R(5),
Aguilar-Salinas CA(6), Ahmadvand A(7), Azizi F(8), Bentham J(9), Cifkova R(10),
Di Cesare M(11), Eriksen L(12), Farzadfar F(13), Ferguson TS(14), Ikeda N(15),
Khalili D(16), Khang YH(17), Lanska V(18), León-Muñoz L(19), Magliano DJ(20),
Margozzini P(21), Msyamboza KP(22), Mutungi G(23), Oh K(24), Oum S(25),
Rodríguez-Artalejo F(19), Rojas-Martinez R(26), Valdivia G(27), Wilks R(14), Shaw
JE(20), Stevens GA(28), Tolstrup JS(12), Zhou B(29), Salomon JA(1), Ezzati M(30),
Danaei G(31).
Author information:
(1)Department of Global Health and Population, Harvard School of Public Health,
Boston, MA, USA.
(2)The George Institute for Global Health, University of Oxford, Oxford, UK; The
George Institute for Global Health, University of Sydney, Sydney, NSW, Australia;
Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
(3)Yale/Yale-New Haven Hospital, Center for Outcomes Research and Evaluation, New
Haven, CT, USA.

(4)Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA.
(5)Central Department of Primary Health Care, Ministry of Health, Kuwait City,
Kuwait.
(6)Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias
Médicas y Nutrición, "Salvador Zubirán", Mexico City, Mexico.
(7)MRC-PHE Centre for Environment and Health, Imperial College London, London,
UK; Department of Epidemiology and Biostatistics, School of Public Health,
Imperial College London, London, UK; Non-Communicable Diseases Research Center,
Endocrinology and Metabolism Population Sciences Institute, Tehran University of
Medical Sciences, Tehran, Iran.
(10)Center for Cardiovascular Prevention, Charles University in Prague, First
Faculty of Medicine and Thomayer Hospital, Prague, Czech Republic.
Imperial College London, London, UK; Department of Natural Sciences, School of
Science and Technology, Middlsex University, London, UK.
(12)National Institute of Public Health, University of Southern Denmark,
Copenhagen, Denmark.
(13)Non-Communicable Diseases Research Center, Endocrinology and Metabolism
Population Sciences Institute, Tehran University of Medical Sciences, Tehran,
Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism
Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
(14)Epidemiology Research Unit, Caribbean Institute for Health Research, The
University of the West Indies, Kingston, Jamaica.
(15)Center for International Collaboration and Partnership, National Institute of
Health and Nutrition, National Institutes of Biomedical Innovation, Health and
Nutrition, Tokyo, Japan.

(17)Institute of Health Policy and Management, Seoul National University College
of Medicine, Seoul, South Korea.
(18)Statistical Unit, Institute for Clinical and Experimental Medicine, Prague,
Czech Republic.
(19)Department of Preventive Medicine and Public Health, School of Medicine,
Universidad Autónoma de Madrid/Idipaz, and CIBER of Epidemiology and Public
Health, Madrid, Spain.
(20)Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
(21)Department of Public Health, Faculty of Medicine, Pontifical Catholic
University of Chile, Santiago, Chile.
(22)WHO, Malawi Country Office, Lilongwe, Malawi.
(23)Non-communicable Diseases Prevention and Control Program at the Ministry of
Health, Kampala, Uganda.
(24)Division of Health and Nutrition Survey, Korea Centers for Disease Control
and Prevention, Cheongwon-gun, South Korea.
(25)University of Health Sciences, Phnom Penh, Cambodia.
(26)Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud
Publica, Cuernavaca, Mexico.
(27)División Salud Pública y Medicina Familiar, Pontificia Universidad Católica
de Chile, Santiago, Chile.
(28)Department of Information, Evidence and Research, WHO, Geneva, Switzerland.
Imperial College London, London, UK; WHO Collaborating Centre on NCD Surveillance
and Epidemiology, Imperial College London, London, UK; Wellcome Trust Centre for
Global Health Research, London, UK.

Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health,
Boston, MA, USA. Electronic address: gdanaei@hsph.harvard.edu.
Comment in
Lancet Diabetes Endocrinol. 2017 Mar;5(3):155-157.
BACKGROUND: Worldwide implementation of risk-based cardiovascular disease (CVD)
prevention requires risk prediction tools that are contemporarily recalibrated
for the target country and can be used where laboratory measurements are
unavailable. We present two cardiovascular risk scores, with and without
laboratory-based measurements, and the corresponding risk charts for 182
countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74
years.
METHODS: Based on our previous laboratory-based prediction model (Globorisk), we
used data from eight prospective studies to estimate coefficients of the risk
equations using proportional hazard regressions. The laboratory-based risk score
included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in
the non-laboratory (office-based) risk score, we replaced diabetes and total
cholesterol with BMI. We recalibrated risk scores for each sex and age group in
each country using country-specific mean risk factor levels and CVD rates. We
used recalibrated risk scores and data from national surveys (using data from
adults aged 40-64 years) to estimate the proportion of the population at
different levels of CVD risk for ten countries from different world regions as
examples of the information the risk scores provide; we applied a risk threshold
for high risk of at least 10% for high-income countries (HICs) and at least 20%
for low-income and middle-income countries (LMICs) on the basis of national and
international guidelines for CVD prevention. We estimated the proportion of men
and women who were similarly categorised as high risk or low risk by the two risk
scores.
FINDINGS: Predicted risks for the same risk factor profile were generally lower
in HICs than in LMICs, with the highest risks in countries in central and
southeast Asia and eastern Europe, including China and Russia. In HICs, the
proportion of people aged 40-64 years at high risk of CVD ranged from 1% for
South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in
low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian
men (using a ≥20% risk threshold). More than 80% of adults were similarly
classified as low or high risk by the laboratory-based and office-based risk
scores. However, the office-based model substantially underestimated the risk
among patients with diabetes.
INTERPRETATION: Our risk charts provide risk assessment tools that are
recalibrated for each country and make the estimation of CVD risk possible
without using laboratory-based measurements.
FUNDING: National Institutes of Health.
DOI: 10.1016/S2213-8587(17)30015-3
PMCID: PMC5354360
172. BMJ Open Diabetes Res Care. 2016 Oct 3;4(1):e000294. eCollection 2016.
Large-scale survey of rates of achieving targets for blood glucose, blood
pressure, and lipids and prevalence of complications in type 2 diabetes (JDDM
40).
Yokoyama H(1), Oishi M(2), Takamura H(3), Yamasaki K(4), Shirabe SI(5), Uchida
D(6), Sugimoto H(7), Kurihara Y(8), Araki SI(9), Maegawa H(9).
Author information:
(1)Department of Internal Medicine , Jiyugaoka Medical Clinic , Obihiro , Japan.
(2)Oishi Clinic , Kyoto , Japan.
(3)Takamura Clinic , Fussa , Japan.
(4)Kawai Clinic , Tsukuba , Japan.
(5)HEC Science Clinic , Yokohama , Japan.
(6)Hotaruno Central Clinic , Kisarazu , Japan.
(7)Sugimoto Clinic , Kitakyushu , Japan.
(8)Kurihara Clinic , Sapporo , Japan.
(9)Department of Medicine , Shiga University of Medical Science , Otsu, Shiga ,
Japan.
OBJECTIVE: The fact that population with type 2 diabetes mellitus and bodyweight
of patients are increasing but diabetes care is improving makes it important to
explore the up-to-date rates of achieving treatment targets and prevalence of
complications. We investigated the prevalence of microvascular/macrovascular
complications and rates of achieving treatment targets through a large-scale
multicenter-based cohort.
RESEARCH DESIGN AND METHODS: A cross-sectional nationwide survey was performed on
9956 subjects with type 2 diabetes mellitus who consecutively attended primary
care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and
macrovascular complications and rates of achieving targets of glycated hemoglobin
(HbA1c) <7.0%, blood pressure <130/80 mm Hg, and lipids of
low-density/high-density lipoprotein cholesterol <3.1/≥1.0 mmol/L and
non-high-density lipoprotein cholesterol <3.8 mmol/L were investigated.
RESULTS: The rates of achieving targets for HbA1c, blood pressure, and lipids
were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular
complications was ∼28% each, 6.4% of which had all microvascular complications,
while that of macrovascular complications was 12.6%. With an increasing duration
of diabetes, the rate of achieving target HbA1c decreased and the prevalence of
each complication increased despite increased use of diabetes medication. The
prevalence of each complication decreased according to the number achieving the 3

treatment targets and was lower in subjects without macrovascular complications
than those with. Adjustments for considerable covariates exhibited that each
complication was closely inter-related, and the achievement of each target was
significantly associated with being free of each complication.
CONCLUSIONS: Almost half of the subjects examined did not meet the recommended
targets. The risk of each complication was significantly affected by 1 on-target
treatment (inversely) and the concomitance of another complication (directly).
Total diabetes care including one-by-one management of modifiable risk factors
and complications may be important for high-quality care. The future studies
including more subjects and clinics with precise complication status are needed.
DOI: 10.1136/bmjdrc-2016-000294
PMCID: PMC5051339
PMID: 27752329
173. Cardiovasc Diabetol. 2018 Oct 30;17(1):139. doi: 10.1186/s12933-018-0782-0.
Left ventricular subclinical myocardial dysfunction in uncomplicated type 2
diabetes mellitus is associated with impaired myocardial perfusion: a
contrast-enhanced cardiovascular magnetic resonance study.
Liu X(1), Yang ZG(1), Gao Y(1), Xie LJ(2), Jiang L(1), Hu BY(1), Diao KY(1), Shi
K(1), Xu HY(1), Shen MT(1), Ren Y(3), Guo YK(4).
Author information:
(1)Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue
Xiang, Chengdu, Sichuan, 610041, China.
(2)Department of Radiology, Key Laboratory of Obstetric & Gynecologic and

Pediatric Diseases and Birth Defects of Ministry of Education, National Key
Laboratory of Biotherapy, West China Second University Hospital, Sichuan
University, 20# South Renmin Road, Chengdu, Sichuan, 610041, China.
(3)Department of Endocrinology and Metabolism, West China Hospital, Sichuan
University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China.
(4)Department of Radiology, Key Laboratory of Obstetric & Gynecologic and
Pediatric Diseases and Birth Defects of Ministry of Education, National Key
Laboratory of Biotherapy, West China Second University Hospital, Sichuan
University, 20# South Renmin Road, Chengdu, Sichuan, 610041, China.
gykpanda@163.com.
BACKGROUND: Early detection of subclinical myocardial dysfunction in patients
with diabetes mellitus (DM) is essential for recommending therapeutic
interventions that can prevent or reverse heart failure, thereby improving the
prognosis in such patients. This study aims to quantitatively evaluate left
ventricular (LV) myocardial deformation and perfusion using cardiovascular
magnetic resonance (CMR) imaging in patients with type 2 diabetes mellitus
(T2DM), and to investigate the association between LV subclinical myocardial
dysfunction and coronary microvascular perfusion.
METHODS: We recruited 71 T2DM patients and 30 healthy individuals as controls who
underwent CMR examination. The T2DM patients were subdivided into two groups,
namely the newly diagnosed DM group (n = 31, patients with diabetes
for ≤ 5 years) and longer-term DM group (n = 40, patients with
diabetes > 5 years). LV deformation parameters, including global peak strain
(PS), peak systolic strain rate, and peak diastolic strain rate (PSDR), and
myocardial perfusion parameters such as upslope, time to maximum signal intensity
(TTM), and max signal intensity (Max SI, were measured and compared among the
three groups. Pearson's correlation was used to evaluate the correlation between
LV deformation and perfusion parameters.
RESULTS: Pooled data from T2DM patients showed a decrease in global longitudinal,
circumferential, and radial PDSR compared to healthy individuals, apart from

lower upslope. In addition, increased TTM and reduced Max SI were found in the
longer-term diabetics compared to the normal subjects (p < 0.017 for all).
Multivariable linear regression analysis showed that T2DM was independently
associated with statistically significant CMR parameters, except for TTM
(β = 0.137, p = 0.195). Further, longitudinal PDSR was significantly associated
with upslope (r = - 0.346, p = 0.003) and TTM (r = 0.515, p < 0.001).
CONCLUSIONS: Our results imply that a contrast-enhanced 3.0T CMR can detect
subclinical myocardial dysfunction and impaired myocardial microvascular
perfusion in the early stages of T2DM, and that the myocardial dysfunction is
associated with impaired coronary microvascular perfusion.
DOI: 10.1186/s12933-018-0782-0
PMCID: PMC6206833
PMID: 30373588
eCollection 2018.
Lifestyle Intervention for the Prevention of Diabetes in Women With Previous
Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Goveia P(1), Cañon-Montañez W(2), Santos DP(1), Lopes GW(1), Ma RCW(3), Duncan
BB(1), Ziegelman PK(1), Schmidt MI(1).
Author information:
(1)Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do
Sul, Porto Alegre, Brazil.
(2)Faculty of Nursing, Universidad de Antioquia, Medellín, Colombia.
Prince of Wales Hospital, Shatin, China.

Background: Type 2 diabetes is increasing among the young, and gestational
diabetes (GDM) offers a unique opportunity for diabetes prevention. We aimed to
systematically review postpartum randomized trials to summarize the benefits of
lifestyle interventions for women with previous GDM. Methods:We searched for RCTs
involving women with previous GDM that compared lifestyle interventions-diet,
physical activity or breastfeeding-at postpartum with usual care up to May 2018.
Results:Of 1,895 abstracts identified, we selected 15 studies investigating
incidence of diabetes or changes in glycemia. Most interventions focused on
changes in diet and physical activity, only one also on incentive to
breastfeeding. Meta-analysis of 8 studies investigating incidence of diabetes
revealed a homogeneous (I2 = 10%), reduction of 25% (RR = 0.75; 95%CI: 0.55-1.03)
borderline statistically significant. Only trials offering intervention soon
after delivery (< 6 months post-partum) were effective (RR = 0.61; 95%CI:
0.40-0.94; p for subgroup comparison = 0.11). Overall, no benefit was found
regarding measures of glycemia. Although moderate reductions in weight (MD =
-1.07 kg; -1.43-0.72 kg); BMI (MD = -0.94 kg/m2; -1.79 -0.09 kg/m2); and waist
circumference (MD = -0.98 cm; -1.75 -0.21 cm) were observed, effects were larger
with longer follow-up. Conclusions:Summary results of the available evidence
support benefits of lifestyle interventions at postpartum for women with previous
GDM. Benefits, although smaller than those of major trials based in older
subjects receiving intensive interventions, appear clinically relevant for this
young subset of woman. Further studies are needed to improve the quality of the
evidence and to further tailor interventions to this specific setting.
DOI: 10.3389/fendo.2018.00583
PMCID: PMC6182069
PMID: 30344509
175. Int J Environ Res Public Health. 2017 Sep 10;14(9). pii: E1041. doi:
10.3390/ijerph14091041.
Lipid Profiles, Glycated Hemoglobin, and Diabetes in People Living at High
Altitude in Nepal.
Aryal N(1), Weatherall M(2), Bhatta YKD(3), Mann S(4).
Author information:
(1)Department of Medicine, University of Otago, Wellington 6021, New Zealand.
nirmal.aryal.2010@gmail.com.
mark.weatherall@otago.ac.nz.
(3)Norvic International Hospital, Kathmandu 14126, Nepal. ykdbhatt@yahoo.com.
stewart@mannz.co.nz.
This study aimed to describe lipid profiles and the distribution of glycated
hemoglobin (HbA1c) in a sample of a high altitude population of Nepal and to
explore associations between these metabolic risk variables and altitude. A
cross-sectional survey of cardiovascular disease and associated risk factors was
conducted among 521 people living at four different altitude levels, all above
2800 m, in the Mustang and Humla districts of Nepal. Urban participants
(residents at 2800 m and 3620 m) had higher total cholesterol (TC) and
triglyceride (TG) than rural participants. A high ratio of TC to high-density
lipoprotein-cholesterol (HDL) (TC/HDL ≥ 5.0) was found in 23.7% (95% CI 19.6,
28.2) and high TG (≥1.7 mmol/L) in 43.3% (95% CI 38.4, 48.3) of participants
overall. Mean HbA1c levels were similar at all altitude levels although urban
participants had a higher prevalence of diabetes. Overall, 6.9% (95% CI 4.7, 9.8)
of participants had diabetes or were on hypoglycaemic treatment. There was no
clear association between lipid profiles or HbA1c and altitude in a multivariate
analysis adjusted for possible confounding variables. Residential settings and

associated lifestyle practices are more strongly associated with lipid profiles
and HbA1c than altitude amongst high altitude residents in Nepal.
DOI: 10.3390/ijerph14091041
PMCID: PMC5615578
176. BMC Res Notes. 2016 Jul 1;9:331. doi: 10.1186/s13104-016-2135-y.
Local networks of community and healthcare organisations: a mixed methods study.
Kemper-Koebrugge W(1), Koetsenruijter J(2), Rogers A(3), Laurant M(4)(2), Wensing
M(2).
Author information:
(1)Faculty of Health and Social Studies, HAN University of Applied Sciences, PO
Box 6960, 6503, Nijmegen, The Netherlands. wendy.kemper@han.nl.
(2)Radboud Institute for Health Sciences, IQ Healthcare Nijmegen, The
Netherlands114-IQ Healthcare, Radboud University Medical Center, PO Box 9101,
6500, Nijmegen, The Netherlands.
(3)Faculty of Health Sciences, NIHR CLAHRC Wessex, University of Southampton,
Highfield Campus Building 67 Room 4017, Southampton, SO17 1BJ, UK.
(4)Faculty of Health and Social Studies, HAN University of Applied Sciences, PO
Box 6960, 6503, Nijmegen, The Netherlands.
BACKGROUND: Local collaboration of community organisations and healthcare
organisations is seen as relevant for the efficiency and efficacy of health and
social care because of their potential role in providing social involvement which
may reduce the need for the utilisation of formal services. Care organisations
connect to each other in different ways, thus comprising an organisational
network. This study aimed to describe and explore organisational networks with
respect to their activities for people with diabetes mellitus type 2 and
potential mechanisms of effective collaboration. Collaboration could include, for
example, referring to each other and organising activities together. Potential
mechanisms are navigation, negotiation and contagion.
METHODS: A mixed methods study was conducted in an urban and a rural area in the
Netherlands. The participating organisations were mentioned by a sample of
diabetes patients in these regions and by organisations' representatives in a
snowballing procedure. Next a quantitative survey and a semi-structured interview
were conducted, including 35 representatives of these local organisations. The
social network analysis methods was used to map and characterise the
organisational networks based on results from the survey. A thematic analysis of
interviews was undertaken to identify how three mechanisms (navigation,
negotiation and contagion) were used in the collaboration.
RESULTS: Both interviews and network structures showed evidence of
navigation-related mechanisms. Organisations referred patients with diabetes to
services within their organisation or to relevant services provided by other
organisations. Hardly any negotiation or contagion-related mechanisms were
identified. If negotiation between organisations was found, it seemed externally
enforced. The density, centrality, and reciprocity in the networks seemed low to
facilitate contagion of practices. Some organisations reported actions that could
have impacted on contagion. Representatives emphasized the need of network
collaboration with local or regional community and healthcare organisations.
CONCLUSION: The study suggests that navigation to resources is a relevant theme
in organisational networks, which could be targeted by interventions. More
research is needed to explore the relevance of other network-related mechanisms.
DOI: 10.1186/s13104-016-2135-y
PMCID: PMC4930621
eCollection 2017.
Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species
production in macrophages.
Zgheib C(1)(2), Hodges MM(1)(2), Hu J(1)(2), Liechty KW(1)(2), Xu J(1)(2).
Author information:
(1)Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora,
Colorado, United States of America.
(2)Department of Surgery, Division of Pediatric Surgery, Children's Hospital
Colorado, Aurora, Colorado, United States of America.
Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized
by insulin resistance and resulting hyperglycemia, which is associated with
impaired wound healing. The clinical complications associated with hyperglycemia
are attributed, in part, to the increased production of reactive oxygen species
(ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important
regulatory roles in many biological processes. Specifically, lncRNA Lethe has
been described as exhibiting an anti-inflammatory effect by binding to the p65
subunit of NFκB and blocking its binding to DNA and the subsequent activation of
downstream genes. We therefore hypothesize that dysregulation of Lethe's
expression plays a role in hyperglycemia-induced ROS production. To test our
hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high
glucose (25 mM) for 24h. High glucose conditions significantly induced ROS
production and NOX2 gene expression in RAW cells, while significantly decreasing
Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the

increased ROS production induced by high glucose conditions, while also
attenuating the upregulation of NOX2 expression. Similar results was found also
in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage
(BMM). Furthermore, overexpression of Lethe in RAW cells treated with high
glucose significantly reduced the translocation of p65-NFkB to the nucleus, which
resulted in decreased NOX2 expression and ROS production. Interestingly, these
findings are consistent with the decreased Lethe gene expression and increased
NOX2 gene expression observed in a mouse model of diabetic wound healing. These
findings provide the first evidence that lncRNA Lethe is involved in the
regulation of ROS production in macrophages through modulation of NOX2 gene
expression via NFκB signaling. Moreover, this is the first report to describe a
role of lncRNAs, in particular Lethe, in impaired diabetic wound healing. Further
studies are warranted to determine if correction of Lethe expression in diabetic
wounds could improve healing.
PMCID: PMC5426762
178. Lancet Diabetes Endocrinol. 2017 Apr;5(4):271-279. doi:
10.1016/S2213-8587(17)30061-X. Epub 2017 Feb 23.
Long-term incidence of microvascular disease after bariatric surgery or usual
care in patients with obesity, stratified by baseline glycaemic status: a
post-hoc analysis of participants from the Swedish Obese Subjects study.
Carlsson LMS(1), Sjöholm K(2), Karlsson C(3), Jacobson P(2), Andersson-Assarsson
JC(2), Svensson PA(2), Larsson I(4), Hjorth S(2), Neovius M(5), Taube M(2),
Carlsson B(3), Peltonen M(6).

Author information:
(1)Institute of Medicine, Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden. Electronic address: lena.carlsson@medic.gu.se.
Gothenburg, Sweden.
Gothenburg, Sweden; AstraZeneca Gothenburg, Mölndal, Sweden.
Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden.
(5)Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet,
Stockholm, Sweden.
(6)Chronic Disease Prevention Unit, National Institute for Health and Welfare,
Helsinki, Finland.
Comment in
Lancet Diabetes Endocrinol. 2017 Jun;5(6):415-416.
Lancet Diabetes Endocrinol. 2017 Jun;5(6):415.
Lancet Diabetes Endocrinol. 2017 Jun;5(6):416-417.
Lancet Diabetes Endocrinol. 2017 Apr;5(4):240-241.
BACKGROUND: Bariatric surgery is associated with remission of diabetes and
prevention of diabetic complications in patients with obesity and type 2
diabetes. Long-term effects of bariatric surgery on microvascular complications
in patients with prediabetes are unknown. The aim of this study was to examine
the effects of bariatric surgery on incidence of microvascular complications in
patients with obesity stratified by baseline glycaemic status.
METHODS: Patients were recruited to the Swedish Obese Subjects (SOS) study
between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years
and BMI of 34 kg/m2 or greater in men and 38 kg/m2 or greater in women. Exclusion
criteria were identical in surgery and control groups and designed to exclude
patients not suitable for surgery. The surgery group (n=2010) underwent gastric
bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty
(1369 [68%]). Participants in the control group (n=2037) received usual care.
Bodyweight was measured and questionnaires were completed at baseline and at 0·5
years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years,
and 20 years. Biochemical variables were measured at baseline and at 2 years, 10
years, and 15 years. We categorised participants into subgroups on the basis of
baseline glycaemic status (normal [fasting blood glucose concentration <5·0
mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at
baseline visit without previous diagnosis], and established diabetes [diagnosis
of diabetes before study inclusion]). We obtained data about first incidence of
microvascular disease from nationwide registers and about diabetes incidence at
study visits at 2 years, 10 years, and 15 years. We did the main analysis by
intention to treat, and subgroup analyses after stratification by baseline
glycaemic status and by diabetes status at the 15 year follow-up. The SOS study
is registered with ClinicalTrials.gov, NCT01479452.
FINDINGS: 4032 of the 4047 participants in the SOS study were included in this
analysis. We excluded four patients with suspected type 1 diabetes, and 11
patients with unknown glycaemic status at baseline. At baseline, 2838 patients
had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes,
and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We
identified 374 incident cases of microvascular disease in the control group and
224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001).
Interaction between baseline glycaemic status and effect of treatment on
incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs
were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed
by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established
diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was
associated with reduced incidence of microvascular events in people with
prediabetes regardless of whether they developed diabetes during follow-up.
INTERPRETATION: Bariatric surgery was associated with reduced risk of
microvascular complications in all subgroups, but the greatest relative risk

reduction was observed in patients with prediabetes at baseline. Our results
suggest that prediabetes should be treated aggressively to prevent future
microvascular events, and effective non-surgical treatments need to be developed
for this purpose.
FUNDING: US National Institutes of Health, Swedish Research Council, Sahlgrenska
University Hospital Regional Agreement on Medical Education and Research, and
Swedish Diabetes Foundation.
DOI: 10.1016/S2213-8587(17)30061-X
PMCID: PMC5394228
179. Sci Rep. 2017 Sep 18;7(1):11267. doi: 10.1038/s41598-017-09753-6.
Low level activity thresholds for changes in NMR biomarkers and genes in high
risk subjects for Type 2 Diabetes.
Herzig KH(1)(2)(3), Leppäluoto J(4), Jokelainen J(5)(6), Meugnier E(7), Pesenti
S(7), Selänne H(8), Mäkelä KA(4), Ahola R(9), Jämsä T(10)(9)(11), Vidal H(7),
Keinänen-Kiukaanniemi S(5)(6).
Author information:
Oulu, Finland. Karl-Heinz.Herzig@oulu.fi.
(2)Department of Gastroenterology and Metabolism, Poznan University of Medical
Sciences, Poznan, Poland. Karl-Heinz.Herzig@oulu.fi.
(3)Medical Research Center and Oulu University Hospital, University of Oulu and
Oulu University Hospital, Oulu, Finland. Karl-Heinz.Herzig@oulu.fi.

Oulu, Finland.
(5)Center for Life Course Health Research, Faculty of Medicine, University of
Oulu, 90014, Oulu, Finland.
(6)Oulu University Hospital, Unit of General Practice, and Health Center of Oulu,
Oulu, Finland.
(7)CarMeN Laboratory, INSERM U1060, INRA U1397, University of Lyon, 69600,
Oullins, France.
(8)Department of Education and Psychology, University of Jyväskylä, Jyväskylä,
Finland.
(9)Research Unit of Medical Imaging, Physics and Technology, University of Oulu,
90014, Oulu, Finland.
(10)Medical Research Center and Oulu University Hospital, University of Oulu and
Oulu University Hospital, Oulu, Finland.
(11)Department of Diagnostic Imaging, Oulu University Hospital, Oulu, Finland.
Our objectives were to determine if there are quantitative associations between
amounts and intensities of physical activities (PA) on NMR biomarkers and changes
in skeletal muscle gene expressions in subjects with high risk for type 2
diabetes (T2D) performing a 3-month PA intervention. We found that PA was
associated with beneficial biomarker changes in a factor containing several VLDL
and HDL subclasses and lipids in principal component analysis (P = <0.01).
Division of PA into quartiles demonstrated significant changes in NMR biomarkers
in the 2nd - 4th quartiles compared to the 1st quartile representing PA of less
than 2850 daily steps (P = 0.0036). Mediation analysis of PA-related reductions
in lipoproteins showed that the effects of PA was 4-15 times greater than those
of body weight or fat mass reductions. In a subset study in highly active
subjects' gene expressions of oxidative fiber markers, Apo D, and G0/G1 Switch
Gene 2, controlling insulin signaling and glucose metabolism were significantly
increased. Slow walking at speeds of 2-3 km/h exceeding 2895 steps/day attenuated
several circulating lipoprotein lipids. The effects were mediated rather by PA

than body weight or fat loss. Thus, lower thresholds for PA may exist for long
term prevention of cardio-metabolic diseases in sedentary overweight subjects.
DOI: 10.1038/s41598-017-09753-6
PMCID: PMC5603534
PMID: 28924247
180. Circulation. 2017 Jul 18;136(3):249-259. doi: 10.1161/CIRCULATIONAHA.117.029190.
Epub 2017 May 18.
Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose
Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL
Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of
Sodium-Glucose Cotransporter-2 Inhibitors).
Kosiborod M(1), Cavender MA(2), Fu AZ(2), Wilding JP(2), Khunti K(2), Holl RW(2),
Norhammar A(2), Birkeland KI(2), Jørgensen ME(2), Thuresson M(2), Arya N(2),
Bodegård J(2), Hammar N(2), Fenici P(2); CVD-REAL Investigators and Study Group*.
Author information:
(1)From Saint Luke's Mid America Heart Institute and University of
Missouri-Kansas City (M.K.); University of North Carolina, Chapel Hill (M.A.C.);
Georgetown University Medical Center, Washington, DC (A.Z.F.); University of
Liverpool, United Kingdom (J.P.W.); University of Leicester, United Kingdom
(K.K.); University of Ulm, Germany (R.W.H.); Karolinska Institutet, Stockholm,
Sweden (A.N., N.H.); University of Oslo, Norway (K.I.B.); Oslo University
Hospital, Norway (K.I.B.); Steno Diabetes Center, Copenhagen, Gentofte, Denmark
(M.E.J.); National Institute of Public Health, Southern Denmark University,
Copenhagen (M.E.J.); Statisticon AB, Uppsala, Sweden (M.T.); AstraZeneca,
Gaithersburg, MD (N.A.); AstraZeneca, Oslo, Norway (J.B.); AstraZeneca

Gothenburg, Sweden (N.H.); and AstraZeneca, Cambridge, United Kingdom (P.F.).
mkosiborod@saint-lukes.org.
(2)From Saint Luke's Mid America Heart Institute and University of
Missouri-Kansas City (M.K.); University of North Carolina, Chapel Hill (M.A.C.);
Georgetown University Medical Center, Washington, DC (A.Z.F.); University of
Liverpool, United Kingdom (J.P.W.); University of Leicester, United Kingdom
(K.K.); University of Ulm, Germany (R.W.H.); Karolinska Institutet, Stockholm,
Sweden (A.N., N.H.); University of Oslo, Norway (K.I.B.); Oslo University
Hospital, Norway (K.I.B.); Steno Diabetes Center, Copenhagen, Gentofte, Denmark
(M.E.J.); National Institute of Public Health, Southern Denmark University,
Copenhagen (M.E.J.); Statisticon AB, Uppsala, Sweden (M.T.); AstraZeneca,
Gaithersburg, MD (N.A.); AstraZeneca, Oslo, Norway (J.B.); AstraZeneca
Gothenburg, Sweden (N.H.); and AstraZeneca, Cambridge, United Kingdom (P.F.).
Comment in
Ann Transl Med. 2017 Dec;5(23 ):470.
Ann Transl Med. 2017 Dec;5(23 ):474.
Ann Transl Med. 2018 Feb;6(3):55.
BACKGROUND: Reduction in cardiovascular death and hospitalization for heart
failure (HHF) was recently reported with the sodium-glucose cotransporter-2
inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who
have atherosclerotic cardiovascular disease. We compared HHF and death in
patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6
countries to determine if these benefits are seen in real-world practice and
across SGLT-2i class.
METHODS: Data were collected via medical claims, primary care/hospital records,
and national registries from the United States, Norway, Denmark, Sweden, Germany,
and the United Kingdom. Propensity score for SGLT-2i initiation was used to match
treatment groups. Hazard ratios for HHF, death, and their combination were
estimated by country and pooled to determine weighted effect size. Death data
were not available for Germany.
RESULTS: After propensity matching, there were 309 056 patients newly initiated
on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each
treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for
53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively.
Baseline characteristics were balanced between the 2 groups. There were 961 HHF
cases during 190 164 person-years follow-up (incidence rate, 0.51/100
person-years). Of 215 622 patients in the United States, Norway, Denmark, Sweden,
and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100
person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years).
Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower
rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51-0.73; P<0.001);
death (hazard ratio, 0.49; 95% confidence interval, 0.41-0.57; P<0.001); and HHF
or death (hazard ratio, 0.54; 95% confidence interval, 0.48-0.60; P<0.001) with
no significant heterogeneity by country.
CONCLUSIONS: In this large multinational study, treatment with SGLT-2i versus
other glucose-lowering drugs was associated with a lower risk of HHF and death,
suggesting that the benefits seen with empagliflozin in a randomized trial may be
a class effect applicable to a broad population of patients with type 2 diabetes
mellitus in real-world practice.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT02993614.
© 2017 The Authors.
DOI: 10.1161/CIRCULATIONAHA.117.029190
PMCID: PMC5515629
181. World J Stem Cells. 2016 Nov 26;8(11):376-383.

Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of
clinical trials.
Labrador-Velandia S(1), Alonso-Alonso ML(1), Alvarez-Sanchez S(1),
González-Zamora J(1), Carretero-Barrio I(1), Pastor JC(1), Fernandez-Bueno I(1),
Srivastava GK(1).
Author information:
(1)Sonia Labrador-Velandia, María Luz Alonso-Alonso, José Carlos Pastor, Iván
Fernandez-Bueno, Girish Kumar Srivastava, Instituto Universitario de
Oftalmobiología Aplicada, Universidad de Valladolid, 47011 Valladolid, Spain.
Retinal and optic nerve diseases are degenerative ocular pathologies which lead
to irreversible visual loss. Since the advanced therapies availability,
cell-based therapies offer a new all-encompassing approach. Advances in the
knowledge of neuroprotection, immunomodulation and regenerative properties of
mesenchymal stem cells (MSCs) have been obtained by several preclinical studies
of various neurodegenerative diseases. It has provided the opportunity to perform
the translation of this knowledge to prospective treatment approaches for
clinical practice. Since 2008, several first steps projecting new treatment
approaches, have been taken regarding the use of cell therapy in patients with
neurodegenerative pathologies of optic nerve and retina. Most of the clinical
trials using MSCs are in I/II phase, recruiting patients or ongoing, and they
have as main objective the safety assessment of MSCs using various routes of
administration. However, it is important to recognize that, there is still a long
way to go to reach clinical trials phase III-IV. Hence, it is necessary to
continue preclinical and clinical studies to improve this new therapeutic tool.
This paper reviews the latest progress of MSCs in human clinical trials for
retinal and optic nerve diseases.

DOI: 10.4252/wjsc.v8.i11.376
PMCID: PMC5120242
PMID: 27928464
Conflict of interest statement: Conflict-of-interest statement: The authors have
no conflicts of interest to disclose.
182. Cardiovasc Res. 2017 Feb 16. doi: 10.1093/cvr/cvx022. [Epub ahead of print]
Metabolic cardiomyopathies - fighting the next epidemic.
Maack C(1), Murphy E(2).
Author information:
(1)Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg,
Germany.
(2)National Institute of Health, Bethesda, MD, USA.
DOI: 10.1093/cvr/cvx022
PMCID: PMC5852643
PMID: 28203832
183. BBA Clin. 2016 Oct 2;7:41-54. doi: 10.1016/j.bbacli.2016.09.003. eCollection 2017
Jun.
Metabolic relationship between diabetes and Alzheimer's Disease affected by
Cyclo(His-Pro) plus zinc treatment.
Song MK(1), Bischoff DS(1), Song AM(2), Uyemura K(3), Yamaguchi DT(1).
Author information:
(1)VA Greater Los Angeles Healthcare System, 16111, Plummer Street, North Hills,
CA 91343; UCLA School of Medicine, 1O833 Le Conte Avenue, Los Angeles, CA 90095.
(2)Kaiser Permanente Medical Center, 13651 Willard Street, Panorama City, CA
91402.
(3)VA Greater Los Angeles Healthcare System, 16111, Plummer Street, North Hills,
CA 91343.
BACKGROUND: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D)
has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment
ameliorated diabetes in rats and similar improvements have been seen in human
patients. Treatment of amyloid precursor protein (APP) transgenic mice with
Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42
protein levels in the brain tissues of the mice.
SCOPE OF REVIEW: Metabolic relationship between AD and T2D will be described with
particular attention to insulin sensitivity and Aβ degradation in brain and
plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in
decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects
on these biochemical parameters will be discussed.
MAJOR CONCLUSION: Stimulation of IDE synthesis is effective for the clinical
treatment of metabolic diseases including AD and T2D.
GENERAL SIGNIFICANCE: Cyclo-Z might be the effective treatment of AD and T2D by
stimulating IDE synthesis.
DOI: 10.1016/j.bbacli.2016.09.003
PMCID: PMC5219633
PMID: 28070499

eCollection 2016.
Metabolic Syndrome and Associated Factors in Adults of the Amazon Region.
França SL(1), Lima SS(1), Vieira JR(1).
Author information:
(1)Institute of Biological Sciences of the Federal University of Pará, Belém,
State of Pará, Brazil.
Metabolic syndrome (MS) plays a key role in the origin of cardiovascular
diseases. Studies on the MS in Brazil are recent, and its epidemiology in more
isolated regions such as the Amazon is still unknown. The study aimed to estimate
the prevalence of MS and associated factors in adults of the Brazilian Amazon.
This study was conducted in 2012-2013. It is a cross-sectional population-based
study, involving 787 adults randomly selected from the urban area of four cities
in the state of Pará, in the Brazilian Eastern Amazon. The participants underwent
anthropometric measurements, laboratory examination, and were questioned about
their lifestyle. MS was defined by the Joint Interim Statement criteria, using
the multiple logistic regression to investigate the potential association of risk
factors with the presence of MS. The overall prevalence of MS was 34.1% (95% CI =
30.8-37.4), increasing linearly with the increasing body mass index and age. From
40-49 years of age, MS was observed in about half of the women (46.0%), while men
only experienced a high prevalence in the fifth decade of life (43.3%). The low
HDL-c (64.4%) and abdominal obesity (58.9%) were higher in women (p < 0.001),
while for men, high blood pressure was significantly higher (p < 0.001).
Individuals aged 40-59 years old (odds ratio [OR] = 3.35 [95% CI = 2.30-4.90]), ≥
60 years old (OR = 5.80 [3.63-9.27]), overweight (OR = 4.17 [2.77-6.29]), and
obese (OR = 8.82 [5.56-13.98]) were more likely to have MS. The study population
experienced high cardiometabolic risk, requiring government efforts to control MS
and related risk factors, especially obesity.

PMCID: PMC5147872
interests exist.
185. Diabetologia. 2018 Jun;61(6):1315-1324. doi: 10.1007/s00125-018-4599-x. Epub 2018
Apr 6.
Metabolomics insights into early type 2 diabetes pathogenesis and detection in
individuals with normal fasting glucose.
Merino J(1)(2), Leong A(2)(3), Liu CT(4), Porneala B(3), Walford GA(1)(2), von
Grotthuss M(2), Wang TJ(5), Flannick J(1)(2), Dupuis J(4)(6), Levy D(6)(7),
Gerszten RE(8)(9), Florez JC(1)(2)(10), Meigs JB(11)(12)(13).
Author information:
(1)Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital,
Boston, MA, USA.
(2)Programs in Metabolism and Medical & Population Genetics, Broad Institute of
MIT and Harvard, Cambridge, MA, USA.
(3)Division of General Internal Medicine, Massachusetts General Hospital, 100
Cambridge St, Boston, MA, 02114, USA.
(4)Department of Biostatistics, Boston University School of Public Health,
Boston, MA, USA.
(5)Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN,
USA.
(6)The Framingham Heart Study, National Heart, Lung and Blood Institute, National
Institutes of Health, Framingham, MA, USA.
(7)The Population Sciences Branch, Division of Intramural Research, National
Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
(8)Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center,
Boston, MA, USA.
(9)Broad Institute of MIT and Harvard Program in Metabolism, Cambridge, MA, USA.
(10)Department of Medicine, Harvard Medical School, Boston, MA, USA.
(11)Programs in Metabolism and Medical & Population Genetics, Broad Institute of
MIT and Harvard, Cambridge, MA, USA. JMEIGS@mgh.harvard.edu.
(12)Division of General Internal Medicine, Massachusetts General Hospital, 100
Cambridge St, Boston, MA, 02114, USA. JMEIGS@mgh.harvard.edu.
(13)Department of Medicine, Harvard Medical School, Boston, MA, USA.
JMEIGS@mgh.harvard.edu.
AIMS/HYPOTHESIS: Identifying the metabolite profile of individuals with normal
fasting glucose (NFG [<5.55 mmol/l]) who progressed to type 2 diabetes may give
novel insights into early type 2 diabetes disease interception and detection.
METHODS: We conducted a population-based prospective study among 1150 Framingham
Heart Study Offspring cohort participants, age 40-65 years, with NFG. Plasma
metabolites were profiled by LC-MS/MS. Penalised regression models were used to
select measured metabolites for type 2 diabetes incidence classification
(training dataset) and to internally validate the discriminatory capability of
selected metabolites beyond conventional type 2 diabetes risk factors (testing
dataset).
RESULTS: Over a follow-up period of 20 years, 95 individuals with NFG developed
type 2 diabetes. Nineteen metabolites were selected repeatedly in the training
dataset for type 2 diabetes incidence classification and were found to improve
type 2 diabetes risk prediction beyond conventional type 2 diabetes risk factors
(AUC was 0.81 for risk factors vs 0.90 for risk factors + metabolites,
p = 1.1 × 10-4). Using pathway enrichment analysis, the nitrogen metabolism
pathway, which includes three prioritised metabolites (glycine, taurine and

phenylalanine), was significantly enriched for association with type 2 diabetes
risk at the false discovery rate of 5% (p = 0.047). In adjusted Cox proportional
hazard models, the type 2 diabetes risk per 1 SD increase in glycine, taurine and
phenylalanine was 0.65 (95% CI 0.54, 0.78), 0.73 (95% CI 0.59, 0.9) and 1.35 (95%
CI 1.11, 1.65), respectively. Mendelian randomisation demonstrated a similar
relationship for type 2 diabetes risk per 1 SD genetically increased glycine (OR
0.89 [95% CI 0.8, 0.99]) and phenylalanine (OR 1.6 [95% CI 1.08, 2.4]).
CONCLUSIONS/INTERPRETATION: In individuals with NFG, information from a discrete
set of 19 metabolites improved prediction of type 2 diabetes beyond conventional
risk factors. In addition, the nitrogen metabolism pathway and its components
emerged as a potential effector of earliest stages of type 2 diabetes
pathophysiology.
DOI: 10.1007/s00125-018-4599-x
PMID: 29626220
186. Sci Rep. 2018 Aug 23;8(1):12681. doi: 10.1038/s41598-018-30714-0.
MicroRNA 375 modulates hyperglycemia-induced enteric glial cell apoptosis and
Diabetes-induced gastrointestinal dysfunction by targeting Pdk1 and repressing
PI3K/Akt pathway.
Chen Y(1), Liu G(1), He F(1), Zhang L(2), Yang K(1), Yu H(3), Zhou J(1), Gan
H(4)(5).
Author information:
(1)The Center of Gerontology and Geriatrics, West China Hospital, Sichuan
University, Chengdu, 610041, China.
(2)Department of elderly digestive, Sichuan Provincial People's Hospital,

Chengdu, 610072, China.
(3)Department of Gastroenterology, West China Hospital, Sichuan University,
Chengdu, 610041, China.
(4)The Center of Gerontology and Geriatrics, West China Hospital, Sichuan
University, Chengdu, 610041, China. ganhuatian123@163.com.
(5)Department of Gastroenterology, West China Hospital, Sichuan University,
Chengdu, 610041, China. ganhuatian123@163.com.
Diabetic neuropathy can damage systemic nervous system, including alteration of
enteric nervous system and subsequent gastrointestinal dysfunction. The effect of
diabetes on enteric glia cell (EGC) is not clear. We investigated the effect of
diabetes and hyperglycemia on EGC, and the role of microRNA375 in modulating EGC
survival in vivo and in vitro. Streptozotocin-induced diabetic mice were
intraperitoneally injected with microRNA375 inhibitor or its negative control.
EGC was transfected with microRNA375 inhibitor or its mimic. Diabetes mice with
gastrointestinal dysfunction showed increased apoptosis of EGC (no difference in
cell numbers) and gene expression of micorRNA375 in the myenteric plexus.
Hyperglycemia triggered apoptosis of EGC in vitro with decreased expression of
Pdk1 and p-Akt, but increased expression of micorRNA375. MicorRNA375 mimic
induced apoptosis of EGC in vitro with repressed Pdk1and p-Akt. MicorRNA375
inhibitor could both prevent hyperglycemia-induced apoptosis of EGC in vitro and
diabetes-induced gastrointestinal dysfunction in vivo. Our results suggest that
diabetes-induced gastrointestinal dysfunction is related to increased apoptosis
of EGC in the myenteric plexus. Hyperglycemia can increase the expression of
microRNA375 and damage EGC survival through PI3K/Akt pathway. MicroRNA375
specific inhibition can prevent hyperglycemia induced EGC damage and
diabetes-induced gastrointestinal dysfunction.
DOI: 10.1038/s41598-018-30714-0
PMCID: PMC6107553
PMID: 30140011
187. Clin Epidemiol. 2017 Nov 3;9:537-544. doi: 10.2147/CLEP.S148101. eCollection
2017.
Mortality in adults with and without diabetes: is the gap widening?
Wang Z(1), Zhang H(2), Liu M(2).
Author information:
(1)Centre for Clinical Research, Faculty of Medicine, The University of
Queensland, Brisbane, QLD, Australia.
(2)Public Health College, Harbin Medical University, Harbin, China.
Objective: We aimed to assess if the gap in mortality between adults with and
without diabetes has widened over time in US adults.
Methods and study design: This cohort study included 44,041 adults with diabetes
from the US National Health Interview Survey between 1986 and 2009 linked to the
National Mortality Index data up to 2011. Each participant with diabetes was
matched to two participants without diabetes by age, sex, race, survey year, and
region of residence (88,082 persons without diabetes). Mortality differences and
hazard ratios were calculated for different time periods defined by three
methods, according to 1) survey years with original follow-up durations, 2)
follow-up calendar years, and 3) survey years with a fixed 3-year follow-up
duration.
Results: Different methods of defining time periods produced substantially
different mortality rates and changing patterns over time. The decline in
mortality was higher when time periods were defined according to survey years
with original follow-up durations than with the fixed 3-year duration. Different
time periods had comparable baseline and attained ages only when the fixed
duration was used. With this method, the gap between adults with and without
diabetes progressively decreased from 224 (95% confidence interval 188-260) in
1992-1994 to 99 (65-132) per 10,000 person-years in 2007-2009. Hazard ratios
declined significantly from 2.12 (1.88-2.38) in 1995-1997 to 1.70 (1.44-2.00) in
2007-2009.
Conclusion: The decline in mortality over time was greater among adults with
diabetes than those without diabetes. The gap in mortality between adults with
diabetes and those without diabetes significantly narrowed in recent years, and
was more than halved over the last 15 years.
DOI: 10.2147/CLEP.S148101
PMCID: PMC5679564
PMID: 29138599
188. Int J Mol Sci. 2016 Sep 7;17(9). pii: E1498. doi: 10.3390/ijms17091498.
Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy.
Bolinger MT(1), Antonetti DA(2).
Author information:
(1)Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and
Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI
48105, USA. bolimark@umich.edu.
(2)Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and
Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI
48105, USA. dantonet@umich.edu.

Diabetic retinopathy is the leading cause of blindness in working age adults, and
is projected to be a significant future health concern due to the rising
incidence of diabetes. The recent advent of anti-vascular endothelial growth
factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy
but a significant subset of patients fail to respond to treatment. Accumulating
evidence indicates that inflammatory cytokines and chemokines other than VEGF may
contribute to the disease process. The current review examines the presence of
non-VEGF cytokines in the eyes of patients with diabetic retinopathy and
highlights mechanistic pathways in relevant animal models. Finally, novel drug
targets including components of the kinin-kallikrein system and emerging
treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies
are discussed. Recognition of non-VEGF contributions to disease pathogenesis may
lead to novel therapeutics to enhance existing treatments for patients who do not
respond to anti-VEGF therapies.
DOI: 10.3390/ijms17091498
PMCID: PMC5037775
Conflict of interest statement: David A. Antonetti has grant support from
NovoNordisk and Unity Bioscience Mark T. Bolinger declares no conflict of
interest. These funding sources had no role in the development or writing of this
review.
189. Int J Gen Med. 2016 Nov 16;9:419-426. eCollection 2016.
Multi-ethnic differences in HbA1c, blood pressure, and low-density-lipid
cholesterol control among South Africans living with type 2 diabetes, after a
4-year follow-up.
Pinchevsky Y(1), Shukla VJ(1), Butkow N(1), Chirwa T(2), Raal F(3).
Author information:
(1)Department of Pharmacy and Pharmacology, School of Therapeutic Sciences.
(2)Division of Epidemiology and Biostatistics, School of Public Health.
(3)Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and
Metabolism, Faculty of Health Sciences, University of the Witwatersrand,
Johannesburg, South Africa.
PURPOSE: Our study set out to examine if disparities in control of glycated
hemoglobin (HbA1c), blood pressure (BP), and low-density-lipoprotein cholesterol
(LDL-C) existed among an urban multi-ethnic cohort of South Africans, living with
type 2 diabetes mellitus (T2DM).
PATIENTS AND METHODS: This longitudinal, retrospective study consisted of 261 men
and women with previously diagnosed T2DM who attended Charlotte Maxeke
Johannesburg Academic Hospital, South Africa across two time periods 2009 and
2013. Demographic and clinical data were extracted from consecutive medical
records. The primary outcome was to determine achievements in HbA1c, BP, and
LDL-C among ethnic groups using evidence-based goals.
RESULTS: The mean age of the cohort was 64 (±10.6) years, females represented
55%, and the self-reported diabetes duration was 16 (±10.6) years as at 2013.
Black Africans (42.9%, n=112 of 261) were more likely to reach the HbA1c target
(<7%) and less likely to have had retinopathy, nephropathy, or cardiovascular
disease. Over two-thirds of mixed-ancestry patients attained the BP target
(<140/80 mmHg), while 90.2% of Caucasians achieved LDL-C goals (<2.5 mmol/L).
Overall, across the ethnic groups studied, we found that HbA1c control
deteriorated over time, although BP levels remained the same and LDL-C levels
drastically improved.
CONCLUSION: There was poor control of HbA1c, BP, and LDL-C across all ethnic
groups. Although a minority achieved recommended targets, some ethnic groups
appeared to have worse control than others. Timely aggressive actions in

particularly high-risk ethnic groups will prevent/delay the complications
commonly associated with T2DM.
DOI: 10.2147/IJGM.S119965
PMCID: PMC5117891
PMID: 27895508
Conflict of interest statement: The authors report no conflicts of interest in
this work.
190. J Diabetes Metab Disord. 2017 Jan 23;16:3. doi: 10.1186/s40200-017-0288-4.
eCollection 2017.
National action plan for non-communicable diseases prevention and control in
Iran; a response to emerging epidemic.
Peykari N(1), Hashemi H(2), Dinarvand R(3), Haji-Aghajani M(4), Malekzadeh R(5),
Sadrolsadat A(6), Sayyari AA(7), Asadi-Lari M(8), Delavari A(9), Farzadfar F(10),
Haghdoost A(11), Heshmat R(12), Jamshidi H(13), Kalantari N(13), Koosha
A(14)(15), Takian A(16), Larijani B(17).
Author information:
(1)Iranian Non Communicable Diseases Committee (INCDC), Ministry of Health and
Medical Education, Tehran, Iran.
(2)INCDC, Ministry of Health and Medical Education, Tehran, Iran.
(3)Food and Drug Organization, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(4)Deputy of Curative Affairs , INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(5)Deputy of Research and Technology, INCDC, Ministry of Health and Medical

Education, Tehran, Iran.
(6)Deputy of Development, Management, and Resources, INCDC, Ministry of Health
and Medical Education, Tehran, Iran.
(7)Deputy of Public Health, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(8)International Affairs, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(9)Digestive Disease Research Center, Tehran University of Medical Sciences, and
INCDC, MOHME, Tehran, Iran.
(10)Non-Communicable Diseases Research Center, EMRI, Tehran University of Medical
(11)Kerman University of Medical Sciences, Kerman, Iran.
(12)Chronic Diseases Research Center, EMRI, Tehran University of Medical
(13)Shahid Beheshti University of Medical Sciences, Tehran, Iran.
(14)Tabriz University of Medical Sciences, Tabriz, Iran.
(15)Center for NCDs control and prevention, and INCDC, MOHME, Tehran, Iran.
(16)Tehran University of Medical Sciences, Tehran, Iran.
(17)INCDC, Ministry of Health and Medical Education, and EMRI, TUMS, Tehran,
Iran.
Emerging Non-communicable diseases burden move United Nation to call for 25%
reduction by 2025 in premature mortality from non-communicable diseases (NCDs).
The World Health Organization (WHO) developed global action plan for prevention
and control NCDs, but the countries' contexts, priorities, and health care system
might be different. Therefore, WHO expects from countries to meet national
commitments to achieve the 25 by 25 goal through adapted targets and action plan.
In this regards, sustainable high-level political statement plays a key role in
rules and regulation support, and multi-sectoral collaborations to NCDs'
prevention and control by considering the sustainable development goals and
universal health coverage factors. Therefore, Iran established the national

authority's structure as Iranian Non Communicable Diseases Committee (INCDC) and
developed NCDs' national action plan through multi-sectoral approach and
collaboration researchers and policy makers. Translation Iran's expertise could
be benefit to mobilizing leadership in other countries for practical action to
save the millions of peoples.
DOI: 10.1186/s40200-017-0288-4
PMCID: PMC5260033
PMID: 28127543
191. PLoS One. 2018 Feb 6;13(2):e0190923. doi: 10.1371/journal.pone.0190923.
eCollection 2018.
A new pathological scoring system by the Japanese classification to predict renal
outcome in diabetic nephropathy.
Hoshino J(1)(2), Furuichi K(3), Yamanouchi M(4), Mise K(5), Sekine A(1), Kawada
M(1), Sumida K(4), Hiramatsu R(4), Hasegawa E(1), Hayami N(4), Suwabe T(4), Sawa
N(4), Hara S(1), Fujii T(6), Ohashi K(7), Kitagawa K(8), Toyama T(3), Shimizu
M(3), Takaichi K(1)(2), Ubara Y(2)(4), Wada T(3)(9).
Author information:
(1)Nephrology Center, Toranomon Hospital, Tokyo, Japan.
(2)Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
(3)Department of Nephrology, Kanazawa University Hospital, Ishikawa, Japan.
(4)Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
(5)Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama
University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
Okayama, Japan.
(6)Department of Pathology, Toranomon Hospital, Tokyo, Japan.

(7)Department of Pathology, Yokohama City University School of Medicine,
Kanagawa, Japan.
(8)Department of Nephrology, Kanazawa Medical Center, Ishikawa, Japan.
(9)Department of Nephrology and Laboratory Medicine, Kanazawa University,
Ishikawa, Japan.
BACKGROUND AND OBJECTIVES: The impact of the newly proposed pathological
classification by the Japan Renal Pathology Society (JRPS) on renal outcome is
unclear. So we evaluated that impact and created a new pathological scoring to
predict outcome using this classification.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter cohort of 493
biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The
association between each pathological factor-Tervaert' and JRPS
classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was
estimated by adjusted Cox regression. The overall pathological risk score
(J-score) was calculated, whereupon its predictive ability for 10-year risk of
renal outcome was evaluated.
RESULTS: The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3,
presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were,
respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were,
respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2,
and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when
dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were
significantly different from each other (p<0.01, log-rank test). After adjusting
clinical factors, the J-score was a significant predictor of renal outcome.
Ability to predict 10-year renal outcome was improved when the J-score was added
to the basic model: c-statistics from 0.661 to 0.685; category-free net
reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated
discrimination improvement, 0.015 (0.003, 0.028, p = 0.02).
CONCLUSIONS: Mesangiolysis, polar vasculosis, and doubling of GBM-features of the
JRPS system-were significantly associated with renal outcome. Prediction of DN

patients' renal outcome was better with the J-score than without it.
PMCID: PMC5800536
192. J Biol Chem. 2016 Aug 26;291(35):18591-9. doi: 10.1074/jbc.C116.744037. Epub 2016
Jul 19.
NHX-5, an Endosomal Na+/H+ Exchanger, Is Associated with Metformin Action.
Kim J(1), Lee HY(1), Ahn J(2), Hyun M(2), Lee I(2), Min KJ(1), You YJ(3).
Author information:
(1)From the Department of Biological Sciences, Inha University, Incheon 22212,
South Korea.
(2)the Department of Biochemistry and Molecular Biology, Virginia Commonwealth
University, Richmond, Virginia 23298, and.
(3)the Department of Biochemistry and Molecular Biology, Virginia Commonwealth
University, Richmond, Virginia 23298, and the Nagoya Research Center for Brain &
Neural Circuits, Graduate School of Science, Nagoya University, Nagoya 464-8602,
Japan yjyou@bio.nagoya-u.ac.jp.
Diabetes is one of the most impactful diseases worldwide. The most commonly
prescribed anti-diabetic drug is metformin. In this study, we identified an
endosomal Na(+)/H(+) exchanger (NHE) as a new potential target of metformin from
an unbiased screen in Caenorhabditis elegans The same NHE homolog also exists in
flies, where it too mediates the effects of metformin. Our results suggest that
endosomal NHEs could be a metformin target and provide an insight into a novel
mechanism of action of metformin on regulating the endocytic cycle.

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI: 10.1074/jbc.C116.744037
PMCID: PMC5000102
193. Nutrients. 2018 Feb 18;10(2). pii: E235. doi: 10.3390/nu10020235.
The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model
for Type 2 Diabetes Mellitus (T2DM).
Subramaniam A(1), Landstrom M(2), Luu A(3), Hayes KC(4).
Author information:
(1)Department of Biology, Brandeis University, Waltham, MA 02454, USA.
avinaash1381@gmail.com.
mlandstrom@brandeis.edu.
aluu@brandeis.edu.
kchayes@brandeis.edu.
Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex
genetic and environmental interactions. No single animal model has so far
mirrored all the characteristics or complications of diabetes in humans. Since
this disease represents a chronic nutritional insult based on a diet bearing a
high glycemic load, the ideal model should recapitulate the underlying dietary
issues. Most rodent models have three shortcomings: (1) they are genetically or
chemically modified to produce diabetes; (2) unlike humans, most require high-fat
feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats
develop diabetes rapidly (8-10 weeks) with high-carbohydrate (hiCHO) diets,
similar to humans, and are protected by high fat (with low glycemic load) intake.
This review describes diabetes progression in the Nile rat, including various
aspects of breeding, feeding, and handling for best experimental outcomes. The
diabetes is characterized by a striking genetic permissiveness influencing
hyperphagia and hyperinsulinemia; random blood glucose is the best index of
disease progression; and kidney failure with chronic morbidity and death are
outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty
liver disease (NAFLD), also described in diabetic humans, results from hepatic
triglyceride and cholesterol accumulation associated with rising blood glucose.
Protection is afforded by low glycemic load diets rich in certain fibers or
polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify
the nutritional factors and underlying genetic and molecular mechanisms that
characterize human T2DM.
DOI: 10.3390/nu10020235
PMCID: PMC5852811
194. J Diabetes Investig. 2018 Nov;9(6):1304-1311. doi: 10.1111/jdi.12837. Epub 2018
Apr 19.
Non-high-density lipoprotein cholesterol is more informative than traditional
cholesterol indices in predicting diabetes risk for women with normal glucose
tolerance.
Liu L(1)(2)(3), Li Q(1)(2)(3), Yuan Z(4), Zhao M(1)(2)(3), Zhang X(1)(2)(3),
Zhang H(1)(2)(3), Zheng D(1)(2)(3), Xu J(1)(2)(3), Gao L(2)(3)(5), Guan
Q(1)(2)(3), Zhao J(1)(2)(3), Proud CG(6)(7), Wang X(6)(7), Hou X(1)(2)(3);
REACTION Study Group.
Author information:
(1)Department of Endocrinology, Shandong Provincial Hospital affiliated to
Shandong University, Jinan, China.
(2)Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan,
China.
(3)Institute of Endocrinology and Metabolism, Shandong Academy of Clinical
Medicine, Jinan, China.
Shandong University, Jinan, China.
(5)Scientific Center, Shandong Provincial Hospital affiliated to Shandong
University, Jinan, China.
(6)Nutrition and Metabolism, South Australian Health and Medical Research
Institute, Adelaide, South Australia, Australia.
(7)School of Biological Sciences, University of Adelaide, Adelaide, South
Australia, Australia.
AIMS/INTRODUCTION: Limited data are available regarding the performance of
non-high-density lipoprotein cholesterol (non-HDL) in predicting incident
diabetes. We aimed to analyze the association between non-HDL and development of
diabetes, and to estimate the cut-off point of non-HDL for discriminating
incident diabetes in people with normal glucose tolerance.
MATERIALS AND METHODS: Of 3,653 middle-aged and elderly Chinese with normal
glucose tolerance at enrollment, 1,025 men and 1,805 women returned to the 3-year
follow up and were involved in the final analysis. Logistic regression analysis
was used to test the association between cholesterol indices and incident
diabetes, and receiver operating characteristic analyses were used to identify

the optimal cut-off of each cholesterol variable for incident diabetes.
RESULTS: Non-HDL was an independent risk factor for diabetes for women, but not
for men. In women, a 1-standard deviation increment in non-HDL was associated
with a 1.43-fold higher risk of diabetes (95% confidence interval 1.14-1.79;
P = 0.002), whereas odds ratios for total cholesterol and low-density lipoprotein
cholesterol were 1.33 (95% confidence interval 1.06-1.67; P = 0.015) and 1.30
(95% confidence interval 1.04-1.64; P = 0.024), respectively. The discriminatory
power and the optimal cut-off value of non-HDL for incident diabetes increased
across body mass index categories. For women with obesity, the threshold of
non-HDL for screening of diabetes was estimated as 3.51 mmol/L.
CONCLUSIONS: Non-HDL had better performance than traditional cholesterol indices
in predicting diabetes in women, but not in men. A body mass index-specific
threshold value for a non-HDL-controlling target is required in the prevention of
type 2 diabetes.
© 2018 The Authors. Journal of Diabetes Investigation published by Asian
Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia,
Ltd.
DOI: 10.1111/jdi.12837
PMCID: PMC6215933
PMID: 29542288
195. Sensors (Basel). 2018 Sep 22;18(10). pii: E3208. doi: 10.3390/s18103208.
Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.
Lin YR(1)(2), Hung CC(3), Chiu HY(4)(5)(6)(7), Chang BH(8), Li BR(9)(10), Cheng
SJ(11)(12), Yang JW(13)(14), Lin SF(15)(16), Chen GY(17)(18).

Author information:
(1)Institute of Biomedical Engineering, College of Electrical and Computer
Engineering, National Chiao Tung University, Hsinchu 300, Taiwan.
yoronglin@gmail.com.
(2)Department of Electrical and Computer Engineering, College of Electrical and
Computer Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
yoronglin@gmail.com.
jhincihong19901008hy@gmail.com.
(4)Department of Dermatology, National Taiwan University Hospital Hsin-Chu
Branch, Hsinchu 30059, Taiwan. extra.owl0430@yahoo.com.tw.
(5)Institute of Biomedical Engineering, College of Medicine and College of
Engineering, National Taiwan University, Taipei 10051, Taiwan.
extra.owl0430@yahoo.com.tw.
(6)Department of Dermatology, National Taiwan University Hospital, Taipei 10002,
Taiwan. extra.owl0430@yahoo.com.tw.
(7)Department of Dermatology, College of Medicine, National Taiwan University,
Taipei 10051, Taiwan. extra.owl0430@yahoo.com.tw.
(8)Department of Applied Chemistry, National Chiao Tung University, Hsinchu
30010, Taiwan. mattc34011239@gmail.com.
liborran@gmail.com.
(10)Department of Applied Chemistry, National Chiao Tung University, Hsinchu
30010, Taiwan. liborran@gmail.com.
shengjen@nctu.edu.tw.

shengjen@nctu.edu.tw.
jiawei@nctu.edu.tw.
jiawei@nctu.edu.tw.
linsf5402@nctu.edu.tw.
linsf5402@nctu.edu.tw.
guanyu@nctu.edu.tw.
(18)Department of Biological Science and Technology, National Chiao Tung
University, Hsinchu 30010, Taiwan. guanyu@nctu.edu.tw.
Diabetes has become a chronic metabolic disorder, and the growing diabetes
population makes medical care more important. We investigated using a portable
and noninvasive contact lens as an ideal sensor for diabetes patients whose tear
fluid contains glucose. The key feature is the reversible covalent interaction
between boronic acid and glucose, which can provide a noninvasive glucose sensor
for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact
lens that exhibits a reversible swelling/shrinking effect to change its
thickness. The difference in thickness can be detected in a picture taken with a
smartphone and analyzed using software. Our novel technique offers the following
capabilities: (i) non-enzymatic and continuous glucose detection with the contact
lens; (ii) no need for an embedded circuit and power source for the glucose
sensor; and (iii) the use of a smartphone to detect the change in thickness of
the contact lens with no need for additional photo-sensors. This technique is
promising for a noninvasive measurement of the glucose level and simple
implementation of glucose sensing with a smartphone.
DOI: 10.3390/s18103208
PMCID: PMC6210255
PMID: 30249021
196. Nutrients. 2017 Jan 19;9(1). pii: E9. doi: 10.3390/nu9010009.
Nutrient Patterns Associated with Fasting Glucose and Glycated Haemoglobin Levels
in a Black South African Population.
Chikowore T(1), Pisa PT(2), van Zyl T(3), Feskens EJ(4), Wentzel-Viljoen E(5)(6),
Conradie KR(7).
Author information:
(1)Centre for Excellence in Nutrition, North-West University, Potchefstroom 2520,
North West Province, South Africa. tinashedoc@gmail.com.
(2)Wits Reproductive Health and HIV Institute, University of the Witwatersrand,
Johannesburg 2000, South Africa. ppisa@wrhi.ac.za.
North West Province, South Africa. tertia.vanzyl@nwu.ac.za.
(4)Division of Human Nutrition, Wageningen University, P.O. Box 17, 6700 AA
Wageningen, The Netherlands. edith.feskens@wur.nl.
North West Province, South Africa. edelweiss-wentzel-viljoen@nwu.ac.za.
(6)Medical Research Council Research Unit for Hypertension and Cardiovascular
Disease, Faculty of Health Sciences, North-West University, Potchefstroom 2520,
South Africa. edelweiss-wentzel-viljoen@nwu.ac.za.

North West Province, South Africa. karin.conradie@nwu.ac.za.
Type 2 diabetes (T2D) burden is increasing globally. However, evidence regarding
nutrient patterns associated with the biomarkers of T2D is limited. This study
set out to determine the nutrient patterns associated with fasting glucose and
glycated haemoglobin the biomarkers of T2D. Factor analysis was used to derive
nutrient patterns of 2010 participants stratified by urban/rural status and
gender. Principal Component Analysis (PCA) was applied to 25 nutrients, computed
from the quantified food frequency questionnaires (QFFQ). Three nutrient patterns
per stratum, which accounted for 73% of the variation of the selected nutrients,
were identified. Multivariate linear regression models adjusted for age, BMI,
smoking, physical activity, education attained, alcohol intake, seasonality and
total energy intake were computed. Starch, dietary fibre and B vitamins driven
nutrient pattern was significantly associated with fasting glucose (β = -0.236
(-0.458; -0.014); p = 0.037) and glycated haemoglobin levels (β = -0.175 (-0.303;
-0.047); p = 0.007) in rural women. Thiamine, zinc and plant protein driven
nutrient pattern was associated with significant reductions in glycated
haemoglobin and fasting glucose ((β = -0.288 (-0.543; -0.033); p = 0.027) and (β
= -0.382 (-0.752; -0.012); p = 0.043), respectively) in rural men. Our results
indicate that plant driven nutrient patterns are associated with low fasting
glucose and glycated haemoglobin levels.
DOI: 10.3390/nu9010009
PMCID: PMC5295053
Nutritional Biomarkers, Gene-Diet Interaction, and Risk Factors for Type 2
Diabetes.
Zheng JS(1), Niu K(2), Jacobs S(3), Dashti H(4), Huang T(5).
Author information:
(1)MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
(2)Nutritional Epidemiology Institute, Tianjin Medical University, Tianjin,
China.
(3)Institute of Public Health, University of Heidelberg, Heidelberg, Germany.
(4)Center for Human Genetic Research, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA.
Singapore.
DOI: 10.1155/2016/8610501
PMCID: PMC5220505
198. Circ Res. 2016 May 27;118(11):1703-5. doi: 10.1161/CIRCRESAHA.116.308999.
Obesity, Diabetes, and Cardiovascular Diseases: A Compendium.
Scherer PE(1), Hill JA(2).
Author information:
(1)From the Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine
(P.E.S., J.A.H.), Cell Biology (P.E.S.), and Cardiology and Molecular Biology
(J.A.H.), University of Texas Southwestern Medical Center, Dallas.

philipp.scherer@utsouthwestern.edu Joseph.Hill@UTSouthwestern.edu.
(2)From the Touchstone Diabetes Center (P.E.S.), Departments of Internal Medicine
(P.E.S., J.A.H.), Cell Biology (P.E.S.), and Cardiology and Molecular Biology
(J.A.H.), University of Texas Southwestern Medical Center, Dallas.
DOI: 10.1161/CIRCRESAHA.116.308999
PMCID: PMC4888905
199. Diabetes Ther. 2018 Feb;9(1):113-124. doi: 10.1007/s13300-017-0347-3. Epub 2017
Dec 7.
Peer Education Group Intervention to Reduce Psychological Insulin Resistance: A
Pilot Mixed-Method Study in a Chinese Population.
Or KY(1), Yip BH(2), Lau CH(1), Chen HH(1), Chan YW(1), Lee KP(3).
Author information:
(1)Department of Family Medicine, Kowloon Central Cluster, Hospital Authority,
East Kowloon General Outpatient Clinic, Hong Kong, China.
(2)Jockey Club School of Public Health and Primary Care, The Chinese University
of Hong Kong, Hong Kong, China.
(3)Jockey Club School of Public Health and Primary Care, The Chinese University
of Hong Kong, Hong Kong, China. lkp032@cuhk.edu.hk.
INTRODUCTION: Psychological insulin resistance (PIR) is common among type II
diabetes (DM) patients. Although interventions to reduce PIR have been suggested,
there is no standardized intervention to reduce PIR. This trial aimed to assess
the preliminary effectiveness of a well-structured interventional patient group
(for sample size calculation for larger trials), as well as the acceptability and
feasibility of this intervention group.
METHODS: This study used a quasi-experimental, mixed-method approach. Fifty-three
patients with DM were recruited to an interventional group that included a
general education of DM and insulin, an insulin pen demonstration, and an
insulin-using peer sharing session. Each group consisted of around 15
participants and lasted for 2 h each. The validated Chinese version of the
insulin treatment appraisal scale (C-ITAS) was administered before, immediately
after, and 1 month after the intervention to measure any changes in the
participants' PIR. Patients were interviewed to assess the acceptability of the
intervention until data saturation.
RESULTS: Repeated measures ANOVA showed that the post-intervention C-ITAS scores
(immediately post group and at 1 month) were lower than the pre-intervention
C-ITAS scores (p < 0.001). Changes in multiple attitudes toward insulin were
detected before and after the group intervention. Ten patient interviews were
conducted and found that the intervention was welcomed by all interviewees; no
discomfort or adverse reactions were reported.
CONCLUSION: Preliminary results showed that patient intervention groups with
general education, insulin pen demonstration, and peer sharing appeared to be
safe, acceptable, and effective in reducing PIR. Larger multicenter trials are
needed to generalize these findings.
DOI: 10.1007/s13300-017-0347-3
PMCID: PMC5801233
PMID: 29218568
A Pilot Study to Assess the Feasibility of the Spanish Diabetes Self-Management
Program in the Basque Country.

Gamboa Moreno E(1), Ochoa de Retana Garcia L(2), Del Campo Pena ME(2), Sánchez
Perez Á(3), Martinez Carazo C(3), Arbonies Ortiz JC(4), Rua Portu MA(5), Piñera
Elorriaga K(6), Zenarutzabeitia Pikatza A(7), Urquiza Bengoa MN(8), Méndez
Sanpedro T(9), Oses Portu A(10), Gorostidi Fano L(10), Aguirre Sorondo MB(11),
Vrotsou K(11), Rotaeche Del Campo R(12).
Author information:
(1)Active Patient Program, Donostialdea Integrated Health Organisation,
Osakidetza, Pasajes San Pedro Health Center, Guipuzcoa, Spain.
(2)Donostialdea Integrated Health Organization, Osakidetza, Pasajes San Pedro
Health Center, C/Marinos No. 1, Pasajes, San Pedro, 20110 Guipuzcoa, Spain.
(3)Research Unit, Primary Care-Organization of Integrated Health Services of
Vizcaya, Osakidetza, Bilbao, Spain.
(4)Donostialdea Integrated Health Organization, Osakidetza, Beraun Health Center,
Renteria, Guipuzcoa, Spain.
(5)Donostialdea Integrated Health Organization, Osakidetza, Bidebieta Health
Center, San Sebastián, Spain.
(6)O + Berri, Basque Institute for Healthcare Innovation, Barakaldo, Vizcaya,
Spain.
(7)Family Medicine and Community Teaching Unit of Vizcaya, Osakidetza, Bilbao,
Spain.
(8)Araba Area, Osakidetza, Olaguibel Health Center, Vitoria-Gasteiz, Spain.
(9)Ezkerraldea Enkarterri Cruces Integrated Health Organization, Osakidetza,
Ortuella Health Center, Ortuella, Vizcaya, Spain.
(10)Bidasoa Integrated Health Organization, Osakidetza, Hondarribia Health
Center, Hondarribia, Guipuzcoa, Spain.
(11)Research Unit, Primary Care-Organization of Integrated Health Services of
Guipuzcoa, Osakidetza, San Sebastián, Spain.
(12)Donostialdea Integrated Health Organization, Osakidetza, Alza Health Center,
San Sebastián, Spain.

Purpose. The purpose of this study was to assess the feasibility of the Spanish
Diabetes Self-Management Program (SDSMP) in the primary care setting of the
Basque Health Service and offer initial estimations of the randomized controlled
trial (RCT) effects. Methods. Ten health centers (HCs) participated in a
single-arm pilot study with a 6-month follow-up period between February 2011 and
June 2012. Recruitment was performed via invitation letters, health
professionals, and the local media. Each intervention group consisted of 8-15
people. The ability of each HC in forming up to 2 groups, participants'
compliance with the course, and coordination and data collection issues were
evaluated. Glycated haemoglobin (HbA1c) was the main outcome variable. Secondary
outcomes were cardiovascular risk factors, drugs consumption, medical visits,
quality of life, self-efficacy, physical exercise, and diet. Results. Two HCs did
not organize a course. A total of 173 patients initiated the program, 2 dropped
out without baseline data, and 90% completed it. No pre-post HbA1c differences
existed. Certain improvements were observed in blood pressure control,
self-efficacy, physical activity, and some dietary habits. Conclusion. The SDSMP
is feasible in our setting. Our experience can be of interest when planning and
conducting this program in similar health settings. The trial is registered with
ClinicalTrials.gov identifier NCT01642394.
DOI: 10.1155/2016/9145673
PMCID: PMC5227166
Conflict of interest statement: The authors declare that they have no competing
interests.
201. J Epidemiol. 2018 Aug 5;28(8):347-352. doi: 10.2188/jea.JE20170048. Epub 2018 Mar
17.
A Point System for Predicting 10-Year Risk of Developing Type 2 Diabetes Mellitus
in Japanese Men: Aichi Workers' Cohort Study.
Yatsuya H(1)(2), Li Y(1), Hirakawa Y(2), Ota A(1), Matsunaga M(1), Haregot HE(2),
Chiang C(2), Zhang Y(2), Tamakoshi K(3), Toyoshima H(4), Aoyama A(2).
Author information:
(1)Department of Public Health, Fujita Health University School of Medicine.
(2)Department of Public Health and Health Systems, Nagoya University Graduate
School of Medicine.
(3)Department of Nursing, Nagoya University School of Health Science.
(4)Education and Clinical Research Training Center, Anjo Kosei Hospital.
BACKGROUND: Relatively little evidence exists for type 2 diabetes mellitus (T2DM)
prediction models from long-term follow-up studies in East Asians. This study
aims to develop a point-based prediction model for 10-year risk of developing
T2DM in middle-aged Japanese men.
METHODS: We followed 3,540 male participants of Aichi Workers' Cohort Study, who
were aged 35-64 years and were free of diabetes in 2002, until March 31, 2015.
Baseline age, body mass index (BMI), smoking status, alcohol consumption, regular
exercise, medication for dyslipidemia, diabetes family history, and blood levels
of triglycerides (TG), high density lipoprotein cholesterol (HDLC) and fasting
blood glucose (FBG) were examined using Cox proportional hazard model. Variables
significantly associated with T2DM in univariable models were simultaneously
entered in a multivariable model for determination of the final model using
backward variable selection. Performance of an existing T2DM model when applied
to the current dataset was compared to that obtained in the present study's
model.
RESULTS: During the median follow-up of 12.2 years, 342 incident T2DM cases were
documented. The prediction system using points assigned to age, BMI, smoking
status, diabetes family history, and TG and FBG showed reasonable discrimination
(c-index: 0.77) and goodness-of-fit (Hosmer-Lemeshow test, P = 0.22). The present
model outperformed the previous one in the present subjects.
CONCLUSION: The point system, once validated in the other populations, could be
applied to middle-aged Japanese male workers to identify those at high risk of
developing T2DM. In addition, further investigation is also required to examine
whether the use of this system will reduce incidence.
DOI: 10.2188/jea.JE20170048
PMCID: PMC6048299
202. PLoS Med. 2016 Jul 12;13(7):e1002080. doi: 10.1371/journal.pmed.1002080.
eCollection 2016 Jul.
Population Approaches to Prevention of Type 2 Diabetes.
White M(1).
Author information:
(1)Centre for Diet & Activity Research, MRC Epidemiology Unit, University of
Cambridge, Cambridge, United Kingdom.
Martin White argues that whole population interventions will be needed in
addition to those targeted to people at high risk in order to respond to the
global challenge of type 2 diabetes.
PMCID: PMC4942121

203. Future Cardiol. 2017 May;13(3):279-296. doi: 10.2217/fca-2017-0019. Epub 2017 Jun
5.
PPARs: regulators of metabolism and as therapeutic targets in cardiovascular
disease. Part II: PPAR-β/δ and PPAR-γ.
Han L(1)(2), Shen WJ(1)(2), Bittner S(1), Kraemer FB(1)(2), Azhar S(1)(2).
Author information:
(1)Geriatrics Research, Education & Clinical Center, VA Palo Alto Health Care
System, Palo Alto, CA 94304, USA.
(2)Division of Endocrinology, Department of Medicine, Stanford University,
Stanford, CA 94305, USA.
The PPARs are a subfamily of three ligand-inducible transcription factors, which
belong to the superfamily of nuclear hormone receptors. In mammals, the PPAR
subfamily consists of three members: PPAR-α, PPAR-β/δ and PPAR-γ. PPARs control
the expression of a large number of genes involved in metabolic homeostasis,
lipid, glucose and energy metabolism, adipogenesis and inflammation. PPARs
regulate a large number of metabolic pathways that are implicated in the
pathogenesis of metabolic diseases such as metabolic syndrome, Type 2 diabetes
mellitus, nonalcoholic fatty liver disease and cardiovascular disease. The aim of
this review is to provide up-to-date information about the biochemical and
metabolic actions of PPAR-β/δ and PPAR-γ, the therapeutic potential of their
agonists currently under clinical development and the cardiovascular disease
outcome of clinical trials of PPAR-γ agonists, pioglitazone and rosiglitazone.
DOI: 10.2217/fca-2017-0019
PMCID: PMC5941699

204. BMC Public Health. 2018 Apr 16;18(1):507. doi: 10.1186/s12889-018-5384-y.
Predictors of elevated capillary blood glucose in overweight railway French
employees: a cross-sectional analysis.
Lucas Garcia EL(1)(2), Debensason D(3)(4), Capron L(3), Flahault A(3)(5), Pommier
J(6).
Author information:
(1)SNCF, Optim'Services - Services Médicaux, 4 rue André Campra CS 20012, 93212,
La Plaine Saint-Denis Cedex, France. emminarie.lucas-garcia@sncf.fr.
(2)Univ Rennes, EHESP, CNRS, ARENES-UMR 6051, F-35000 Rennes, France.
emminarie.lucas-garcia@sncf.fr.
(3)SNCF, Optim'Services - Services Médicaux, 4 rue André Campra CS 20012, 93212,
La Plaine Saint-Denis Cedex, France.
(4)CPRP SNCF, Échelon National du Contrôle Médical, Marseille, France.
(5)Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva,
Switzerland.
(6)Univ Rennes, EHESP, CNRS, ARENES-UMR 6051, F-35000 Rennes, France.
BACKGROUND: Hyperglycaemia is a risk factor of cardiovascular disease and a high
risk state for progression to type 2 diabetes. Moreover, overweight, defined as a
body mass index (BMI) between 25 and 29.9 kg/m2, increases the risk of diabetes.
Information about the feasibility of measuring, during routine occupational
health examinations, predictors of elevated capillary blood glucose in overweight
individuals is scarce. This study aims to identify factors that are associated
with elevated capillary blood glucose and can be routinely measured in French
overweight employees to develop targeted preventive strategies in the workplace.
METHODS: Cross-sectional study based on data collected during a workplace health

promotion programme of the French National Railways Company (SNCF) from January
2011 to March 2015. A self-administered questionnaire was completed by overweight
volunteers during the routine occupational health examination. Data collected
included health, anthropometric, sociodemographic, occupational, and lifestyle
characteristics. Elevated capillary blood glucose was defined as capillary blood
glucose equal to or higher than 7 mmol/L. Multivariate logistic regression
analysis was used to examine factors associated with elevated capillary blood
glucose and results were described with odds ratios (OR) and 95% confidence
intervals (CI).
RESULTS: The analysis concerned 2248 overweight employees (mean age: 43 years)
with complete data (total population: 7724). The prevalence of elevated capillary
blood glucose was 20.0%. In the multivariate analysis, significant predictors of
elevated capillary blood glucose were: male sex (OR 1.66, 95% CI 1.21-2.28),
age ≥ 50 years (OR 1.61, 95% CI 1.01-2.55), high blood pressure (OR 1.35, 95% CI
1.07-1.69), and daily intake of sugary food (OR 1.53, 95% CI 1.17-2.00). No
association with occupational characteristics (work schedule, job seniority,
professional grade, and job sector) was found possibly due to lack of statistical
power.
CONCLUSIONS: Our findings provide information for setting up specific diabetes
prevention strategies in the workplace. Overweight men, aged 50 and older, with
high blood pressure and daily sugary food intake should be considered for
capillary blood glucose measurements during their occupational medical
surveillance. Hypertension screening and management as well as health policy
measures to target sugary food consumption could be included in workplace
prevention strategies.
DOI: 10.1186/s12889-018-5384-y
PMCID: PMC5902963
PMID: 29661173
205. Int J Epidemiol. 2018 Apr 1;47(2):399-408. doi: 10.1093/ije/dyx228.
Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes.
Meng R(1), Lv J(1)(2), Yu C(1), Guo Y(3), Bian Z(3), Yang L(4), Chen Y(4), Zhang
H(5), Chen X(6), Chen J(7), Chen Z(4), Qi L(8)(9), Li L(1)(3); China Kadoorie
Biobank Collaborative Group.
Author information:
(1)Peking University Health Science Center, Beijing, China.
(2)Peking University Institute of Environmental Medicine, Beijing, China.
(3)Chinese Academy of Medical Sciences, Beijing, China.
(4)Nuffield Department of Population Health, University of Oxford, Oxford, UK.
(5)Maiji Center for Disease Control and Prevention, Maiji, China.
(6)Sichuan Center for Disease Control and Prevention, Chengdu, China.
(7)China National Center for Food Safety Risk Assessment, Beijing, China.
(8)School of Public Health and Tropical Medicine, Tulane University, New Orleans,
LA, USA.
(9)Harvard School of Public Health, Boston, MA, USA.
Background: Prenatal exposure to famine and adulthood obesity have been
independently related to the risk of type 2 diabetes; however, little is known
about the joint effects of these risk factors at different stages of life on
adulthood diabetes risk.
Methods: The analysis included 88 830 participants of the China Kadoorie Biobank,
who were born around the time of the Chinese Great Famine and without diabetes,
cardiovascular diseases, or cancer at baseline. We defined famine exposure
subgroups as nonexposed (born between 1 October 1962 and 30 September 964),
fetal-exposed (born between 1 October 1959 and 30 September 1961) and
early-childhood exposed (born between 1 October 1956 and 30 September 1958).
General obesity was assessed by body mass index (BMI: overweight ≥ 24.0,

obesity ≥ 28.0) and abdominal obesity assessed by waist-to-hip ratio (WHR,
men/women: moderate ≥ 0.90/0.85, high ≥ 0.95/0.90).
Results: During a median 7.3 years (642 552 person-years) of follow-up, we
identified 1372 incident cases of type 2 diabetes. Compared with nonexposed and
early-childhood exposed participants combined as a single comparison group,
fetal-exposed participants showed an increased risk of diabetes in adulthood
[hazard ratio (HR) = 1.25; 95% confidence interval (CI): 1.07-1.45]. The
association between general obesity and diabetes was consistent across subgroups
according to famine exposure (P for interaction > 0.05). A stronger association
between abdominal obesity and diabetes was observed in the fetal-exposed subgroup
than in other subgroups (P for interaction = 0.025 in the whole population). This
interaction was more obvious in women (P = 0.013) but not in men (P = 0.699).
Compared with normal-BMI and -WHR participants, those with both general
(BMI ≥ 24.0) and abdominal (WHR ≥ 0.90/0.85) obesity in adulthood had 5.32 (95%
CI: 3.81-7.43)-, 3.13 (2.48-3.94)- and 4.43 (3.45-5.68)-fold higher risks if
these were carried during, before and after times of famine, respectively.
Conclusions: Coexistence of prenatal experience of undernutrition and abdominal
obesity in adulthood was associated with a higher risk of type 2 diabetes.
DOI: 10.1093/ije/dyx228
PMCID: PMC5913613
PMID: 29161448
206. Curr Diab Rep. 2016 Dec;16(12):124.
Presence and Risk Factors for Glaucoma in Patients with Diabetes.
Song BJ(1), Aiello LP(2), Pasquale LR(3)(4).
Author information:
(1)Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard
Medical School, 243 Charles Street, Boston, MA, 02114, USA.
Brian_Song@meei.harvard.edu.
(2)Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, 1
Joslin Place, Boston, MA, 02115, USA.
(3)Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard
Medical School, 243 Charles Street, Boston, MA, 02114, USA.
(4)Channing Division of Network Medicine, Brigham and Women's Hospital, 181
Longwood Avenue, Boston, MA, 02215, USA.
Diabetes mellitus represents a growing international public health issue with a
near quadrupling in its worldwide prevalence since 1980. Though it has many known
microvascular complications, vision loss from diabetic retinopathy is one of the
most devastating for affected individuals. In addition, there is increasing
evidence to suggest that diabetic patients have a greater risk for glaucoma as
well. Though the pathophysiology of glaucoma is not completely understood, both
diabetes and glaucoma appear to share some common risk factors and
pathophysiologic similarities with studies also reporting that the presence of
diabetes and elevated fasting glucose levels are associated with elevated
intraocular pressure-the primary risk factor for glaucomatous optic neuropathy.
While no study has completely addressed the possibility of detection bias, most
recent epidemiologic evidence suggests that diabetic populations are likely
enriched with glaucoma patients. As the association between diabetes and glaucoma
becomes better defined, routine evaluation for glaucoma in diabetic patients,
particularly in the telemedicine setting, may become a reasonable consideration
to reduce the risk of vision loss in these patients.
DOI: 10.1007/s11892-016-0815-6
PMCID: PMC5310929

207. BMC Public Health. 2018 Nov 7;18(Suppl 3):1215. doi: 10.1186/s12889-018-6053-x.
Prevalence and factors associated with pre-diabetes and diabetes mellitus in
Kenya: results from a national survey.
Mohamed SF(1)(2), Mwangi M(3)(4), Mutua MK(5), Kibachio J(4)(6), Hussein A(3)(4),
Ndegwa Z(4), Owondo S(4), Asiki G(5), Kyobutungi C(5).
Author information:
(1)Health and Systems for Health Unit, African Population and Health Research
Center (APHRC), Nairobi, Kenya. smohamed@aphrc.org.
(2)Division of Health Sciences, Warwick Medical School, University of Warwick,
Coventry, UK. smohamed@aphrc.org.
(3)Field Epidemiology and Laboratory Training Programme, Ministry of Health,
Nairobi, Kenya.
(4)NCD unit, Ministry of Health, Nairobi, Kenya.
(5)Health and Systems for Health Unit, African Population and Health Research
Center (APHRC), Nairobi, Kenya.
(6)The Institute of Global Health, Faculty of Medicine, University of Geneva
(UNIGE), Geneva, Switzerland.
BACKGROUND: Diabetes Mellitus is one of the four major non-communicable diseases
causing about 4 million deaths in 2017. By 2040, low income countries are
projected to experience 92% increase in mortality due to diabetes. Undiagnosed
diabetes poses a public health concern with costly public health implications
especially in Africa. It is therefore crucial to examine the burden and risk
factors for diabetes at national level to inform policy and national programs.
METHODS: Data from the 2015 Kenya national STEPs survey of adults aged
18-69 years were used. Pre-diabetes was defined as impaired fasting blood glucose
level (6.1 mmol/l to < 7 mmol/l) while diabetes was defined as impaired fasting
blood glucose level ≥ 7 mmol/l. Descriptive statistics were used to determine the
prevalence of pre-diabetes and diabetes and logistic regression was used to
identify associated factors.
RESULTS: Complete data for 4069 respondents (51% females), with 46% aged 18-29
and 61% in rural areas were analyzed. The age-standardized prevalence for
pre-diabetes and diabetes were 3.1% (95% CI: 2.2, 4.0) and 2.4% (1.8, 3.0)
respectively. Only 43.7% were aware of their glycemic condition, one in five of
those who had diabetes had received treatment, and only 7% of those diagnosed
with diabetes had their blood glucose under control. Primary education ((both
incomplete (0.21, 95%CI 0.10-0.47) and complete (0.40, 95%CI 0.23-0.71)) were
associated with lower odds of pre-diabetes. Older age (60-69 years, AOR; 5.6,
95%CI 2.1-15.1) and raised blood pressure (2.8, 95% CI 1.5-5.0) were associated
diabetes while overweight/obesity among women was associated with diabetes.
CONCLUSION: The overall diabetes prevalence in Kenya is consistent with what has
been reported in other sub-Saharan African countries. Of concern is the higher
prevalence of pre-diabetes and undiagnosed diabetes that can progress to
complications in the absence of interventions and the low diabetes awareness and
control. This is the first nationally representative study to identify important
groups at risk of pre-diabetes and diabetes that can be targeted for screening,
health promotion and treatment.
DOI: 10.1186/s12889-018-6053-x
PMCID: PMC6218998
PMID: 30400865
eCollection 2017.
Prevalence and unmet need for diabetes care across the care continuum in a
national sample of South African adults: Evidence from the SANHANES-1, 2011-2012.
Stokes A(1), Berry KM(1), Mchiza Z(2), Parker WA(2), Labadarios D(2), Chola L(2),
Hongoro C(2), Zuma K(2), Brennan AT(1)(3), Rockers PC(1), Rosen S(1)(3).
Author information:
(1)Department of Global Health, Boston University School of Public Health,
Boston, Massachusetts, United Stated of America.
(2)Population Health, Health Systems and Innovation, Human Sciences Research
Council, Cape Town, South Africa.
(3)Health Economics and Epidemiology Research Office, Department of Internal
Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of
Witwatersrand, Johannesburg, South Africa.
South Africa faces an epidemic of chronic non-communicable diseases (NCDs), yet
national surveillance is limited due to the lack of recent data. We used data
from the first comprehensive national survey on NCDs-the South African National
Health and Nutrition Examination Survey (SANHANES-1 (2011-2012))-to evaluate the
prevalence of and health system response to diabetes through a diabetes care
cascade. We defined diabetes as a Hemoglobin A1c equal to or above 6.5% or
currently on treatment for diabetes. We constructed a diabetes care cascade by
categorizing the population with diabetes into those who were unscreened,
screened but undiagnosed, diagnosed but untreated, treated but uncontrolled, and
treated and controlled. We then used multivariable logistic regression models to
explore factors associated with diagnosed and undiagnosed diabetes. The
age-standardized prevalence of diabetes in South Africans aged 15+ was 10.1%.
Prevalence rates were higher among the non-white population and among women.
Among individuals with diabetes, a total of 45.4% were unscreened, 14.7% were
screened but undiagnosed, 2.3% were diagnosed but untreated, 18.1% were treated
but uncontrolled, and 19.4% were treated and controlled, suggesting that 80.6% of
the diabetic population had unmet need for care. The diabetes care cascade
revealed significant losses from lack of screening, between screening and

diagnosis, and between treatment and control. These results point to significant
unmet need for diabetes care in South Africa. Additionally, this analysis
provides a benchmark for evaluating efforts to manage the rising burden of
diabetes in South Africa.
PMCID: PMC5624573
209. Cardiovasc J Afr. 2018 Mar/Apr 23;29(2):73-81. doi: 10.5830/CVJA-2017-047. Epub
2017 Dec 14.
Prevalence, awareness, treatment and control of hypertension, diabetes and
hypercholesterolaemia among adults in Dande municipality, Angola.
Pedro JM(1), Brito M(2), Barros H(3).
Author information:
(1)CISA, Centro de Investigação em Saúde de Angola, Caxito, Angola; EPIUnit,
Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal. Email:
joao.almeidapedro@cisacaxito.org.
(2)Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de
Lisboa, Lisboa, Portugal.
(3)EPIUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal;
Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
OBJECTIVES: To estimate the prevalence, awareness, treatment and control of
hypertension, diabetes and hypercholesterolaemia in an Angolan population aged 15
to 64 years and to determine relationships with sociodemographic, behavioural and
anthropometric characteristics.
METHODS: A total of 2 354 individuals were assessed for behavioural,
sociodemographic and physical characteristics in a cross-sectional,
community-based survey. Post-stratification survey weights were applied to obtain
prevalence levels. Adjusted odds ratios for each variable related to the
conditions were calculated using logistic regression models.
RESULTS: Overall, the prevalence of hypertension was 18.0%, diabetes 9.2% and
hypercholesterolaemia 4.0%. Among hypertensive individuals, the awareness rate
was 48.5%; 15.8% were on treatment and 9.1% had their blood pressure controlled.
Only 10.8% were aware they had diabetes, 4.5% were on treatment and 2.7% were
controlled. The awareness level for hypercholesterolaemia was 4.2%, with 1.4%
individuals on treatment and 1.4% controlled.
CONCLUSION: The prevalence levels of hypertension and diabetes, which were higher
than previous findings for the region, together with the observed low rates of
awareness, treatment and control of all conditions studied, constitute an
additional challenge to the regional health structures, which must rapidly adapt
to the epidemiological shift occurring in this population.
DOI: 10.5830/CVJA-2017-047
PMCID: PMC6008895
PMID: 29293258
210. Hypertension. 2017 Aug;70(2):267-274. doi: 10.1161/HYPERTENSIONAHA.117.09026.
Epub 2017 May 30.
Prevalence, Correlates, and Prognosis of Healthy Vascular Aging in a Western
Community-Dwelling Cohort: The Framingham Heart Study.
Niiranen TJ(1), Lyass A(2), Larson MG(2), Hamburg NM(2), Benjamin EJ(2), Mitchell
GF(2), Vasan RS(2).

Author information:
(1)From the National Heart, Lung, and Blood Institute's and Boston University's
Framingham Heart Study, MA (T.J.N., A.L., M.G.L., E.J.B., R.S.V.); Department of
Mathematics and Statistics, Boston University, MA (A.L., M.G.L.); Department of
Biostatistics (M.G.L.), Evans Department of Medicine, Whitaker Cardiovascular
Institute (N.M.H., E.J.B., R.S.V.), Section of Cardiology, Department of Medicine
(N.M.H., E.J.B., R.S.V.), Section of Vascular Biology, Department of Medicine
(N.M.H.), Section of Preventive Medicine, Department of Medicine (E.J.B.,
R.S.V.), and Department of Epidemiology (E.J.B., R.S.V.), Boston University
School of Public Health, MA; and Cardiovascular Engineering, Inc, Norwood, MA
(G.F.M.). teemu.niiranen@thl.fi.
(2)From the National Heart, Lung, and Blood Institute's and Boston University's
Framingham Heart Study, MA (T.J.N., A.L., M.G.L., E.J.B., R.S.V.); Department of
Mathematics and Statistics, Boston University, MA (A.L., M.G.L.); Department of
Biostatistics (M.G.L.), Evans Department of Medicine, Whitaker Cardiovascular
Institute (N.M.H., E.J.B., R.S.V.), Section of Cardiology, Department of Medicine
(N.M.H., E.J.B., R.S.V.), Section of Vascular Biology, Department of Medicine
(N.M.H.), Section of Preventive Medicine, Department of Medicine (E.J.B.,
R.S.V.), and Department of Epidemiology (E.J.B., R.S.V.), Boston University
School of Public Health, MA; and Cardiovascular Engineering, Inc, Norwood, MA
(G.F.M.).
Comment in
Hypertension. 2017 Aug;70(2):229-231.
Hypertension and increased vascular stiffness are viewed as inevitable parts of
aging. To elucidate whether the age-related decrease in vascular function is
avoidable, we assessed the prevalence, correlates, and prognosis of healthy
vascular aging (HVA) in 3196 Framingham Study participants aged ≥50 years. We
defined HVA as absence of hypertension and pulse wave velocity <7.6 m/s (mean+2
SD of a reference sample aged <30 years). Overall, 566 (17.7%) individuals had
HVA, with prevalence decreasing from 30.3% in people aged 50 to 59 to 1% in those
aged ≥70 years. In regression models adjusted for physical activity, caloric
intake, and traditional cardiovascular disease (CVD) risk factors, we observed
that lower age, female sex, lower body mass index, use of lipid-lowering drugs,
and absence of diabetes mellitus were cross-sectionally associated with HVA
(P<0.001 for all). A unit increase in a cardiovascular health score (Life's
Simple 7) was associated with 1.55-fold (95% confidence interval, 1.38-1.74) age-
and sex-adjusted odds of HVA. During a follow-up of 9.6 years, 391 CVD events
occurred. In Cox regression models adjusted for traditional CVD risk factors,
including blood pressure, HVA was associated with a hazard ratio of 0.45 (95%
confidence interval, 0.26-0.77) for CVD relative to absence of HVA. Although HVA
is achievable in individuals acculturated to a Western lifestyle, maintaining
normal vascular function beyond 70 years of age is challenging. Although our data
are observational, our findings support prevention strategies targeting
modifiable factors and behaviors and obesity, in particular, to prevent or delay
vascular aging and the associated risk of CVD.
© 2017 American Heart Association, Inc.
DOI: 10.1161/HYPERTENSIONAHA.117.09026
PMCID: PMC5509504
211. BMJ Open. 2018 Sep 24;8(9):e020768. doi: 10.1136/bmjopen-2017-020768.
Prevalence of depression in patients with type 2 diabetes mellitus in Spain (the
DIADEMA Study) : results from the MADIABETES cohort.
Salinero-Fort MA(1)(2), Gómez-Campelo P(3)(4), San Andrés-Rebollo FJ(5),
Cárdenas-Valladolid J(6), Abánades-Herranz JC(7), Carrillo de Santa Pau E(8),

Chico-Moraleja RM(9), Beamud-Victoria D(10), de Miguel-Yanes JM(11),
Jimenez-Garcia R(12), López-de-Andres A(12), Ramallo-Fariña Y(2), De Burgos-Lunar
C(2)(13); MADIABETES Research Group.
Collaborators: Am SD, Sanz-Pascual M, Arnalte-Barrera M, Pulido-Fernández S,
Donaire-Jiménez EM, Montero-Lizana C, Domínguez-Paniagua M, Serrano-Simarro P,
Nicolás RE, Gil-Díaz P, Cerrada-Somolinos I, Martín-Cano R, Cava-Rosado A,
Mesonero-Grandes T, Gómez-Navarro E, Maestro-Martín A, Muñoz-Cildoz A,
Calonge-García M, Martín-Bun M, Carreño-Freire P, Fernández-García J,
Morán-Escudero A, Martínez-Irazusta J, Calvo-García E, Alayeto-Sánchez AM,
Reyes-Madridejos C, Bedoya-Frutos M, López-Sabater B, Innerarity-Martínez J,
Rosillo-González A, Menéndez-Fernández A, Mata-Benjumea F, Vich-Pérez P,
Martín-Madrazo C, Gomara-Martínez M, Bello-González C, Pinilla-Carrasco A,
Camarero-Shelly M, Cano-Espin A, Martin JC, Llama-Arauz B, Miguel-Ballano A,
García-Alonso M, García-Pascual JN, González-García MI, López-Rodríguez C,
Miguel-Garzón M, Montero-García MC, Muñoz-Quiros-Aliaga S, Núñez-Palomo S,
Olmos-Carrasco O, Pertierra-Galindo N, Reviriego-Jaén G, Rius-Fortea P,
Rodríguez-Castro G, Vicente-Rodríguez JS, Serrano-Serrano ME, Zamora-Gómez MM,
Zazo-Lázaro MP.
Author information:
(1)Subdirección General de Investigación Sanitaria, Consejería de Sanidad,
Madrid, Spain.
(2)Nodo Madrid, Red de Investigación en Servicios de Salud en Enfermedades
Crónicas (REDISSEC), Madrid, Spain.
(3)Grupo Respuesta Inmune Innata. Hospital La Paz Institute for Health Research
(IdiPAZ), La Paz University Hospital, Madrid, Spain.
(4)Centro de Ciencias de la Salud San Rafael, Universidad Antonio de Nebrija,
Madrid, Spain.
(5)Centro de Salud Las Calesas, Servicio Madrileño de Salud, Madrid, Spain.
(6)Gerencia Adjunta de Planificación y Calidad, Gerencia de Atención Primaria,

Servicio Madrileño de Salud, Madrid, Spain.
(7)Centro de Salud Monóvar, Sevicio Madrileño de Salud, Madrid, Spain.
(8)Grupo de Biología Computacional, Instituto Madrileño de Estudios
Avanzados-IMDEA, Madrid, Spain.
(9)Servicio de Ortopedia y Traumatología, Hospital Central de la Defensa, Madrid,
Spain.
(10)Centro de Salud Felipe II, Madrid, Spain.
(11)Servicio de Medicina Interna, Hospital Gregorio Marañón, Madrid, Spain.
(12)Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón,
Madrid, Spain.
(13)Servicio de Medicina Preventiva, Hospital Clínico San Carlos, Madrid, Spain.
OBJECTIVE: To estimate the prevalence of depression in patients diagnosed with
type 2 diabetes mellitus (T2DM), and to identify sociodemographic, clinical and
psychological factors associated with depression in this population.
Additionally, we examine the annual incidence rate of depression among patients
with T2DM.
METHODS: We performed a large prospective cohort study of patients with T2DM from
the Madrid Diabetes Study. The first recruitment drive included 3443 patients.
The second recruitment drive included 727 new patients. Data have been collected
since 2007 (baseline visit) and annually during the follow-up period (since
2008).
RESULTS: Depression was prevalent in 20.03% of patients (n=592; 95% CI 18.6% to
21.5%) and was associated with previous personal history of depression (OR 6.482;
95% CI 5.138 to 8.178), mental health status below mean (OR 1.423; 95% CI 1.452
to 2.577), neuropathy (OR 1.951; 95% CI 1.423 to 2.674), fair or poor
self-reported health status (OR 1.509; 95% CI 1.209 to 1.882), treatment with
oral antidiabetic agents plus insulin (OR 1.802; 95% CI 1.364 to 2.380), female
gender (OR 1.333; 95% CI 1.009 to 1.761) and blood cholesterol level (OR 1.005;
95% CI 1.002 to 1.009). The variables inversely associated with depression were:
being in employment (OR 0.595; 95% CI 0.397 to 0.894), low physical activity (OR
0.552; 95% CI 0.408 to 0.746), systolic blood pressure (OR 0.982; 95% CI 0.971 to
0.992) and social support (OR 0.978; 95% CI 0.963 to 0.993). In patients without
depression at baseline, the incidence of depression after 1 year of follow-up was
1.20% (95% CI 1.11% to 2.81%).
CONCLUSIONS: Depression is very prevalent among patients with T2DM and is
associated with several key diabetes-related outcomes. Our results suggest that
previous mental status, self-reported health status, gender and several
diabetes-related complications are associated with differences in the degree of
depression. These findings should alert practitioners to the importance of
detecting depression in patients with T2DM.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No
commercial re-use. See rights and permissions. Published by BMJ.
DOI: 10.1136/bmjopen-2017-020768
PMCID: PMC6157517
PMID: 30249627
212. Scand Cardiovasc J. 2017 Aug;51(4):183-189. doi: 10.1080/14017431.2017.1311023.
Epub 2017 Apr 3.
Prevalence of heart failure in the elderly and future projections: the
AGES-Reykjavík study.
Danielsen R(1)(2), Thorgeirsson G(1)(3)(2), Einarsson H(1), Ólafsson Ö(3),
Aspelund T(3)(2), Harris TB(4), Launer L(4), Gudnason V(3)(2).
Author information:
(1)a The Department of Cardiology , Landspítali University Hospital , Reykjavík ,
Iceland.
(2)c The University of Iceland , Reykjavík , Iceland.
(3)b The Icelandic Heart Association Research Institute , Kópavogur , Iceland.
(4)d Laboratory of Epidemiology and Population Sciences, National Institute of
Aging , Bethesda , MD , USA.
OBJECTIVES: To assess the prevalence of heart failure (HF) in a randomly selected
study population of elderly individuals representing the general population of
Iceland. Furthermore, to project the number of individuals likely to have HF in
the future.
DESIGN: Baseline characteristics and clinical data from 5706 individuals who
participated in the population based AGES-Reykjavik Study and gave their informed
consent were used. Their age range was 66-98 years (mean age 77.0 ± 5.9 years),
57.6% were females. HF-diagnoses were established by review of hospital records
and adjudicated according to prespecified criteria. Data from the 'Statistics
Iceland' institution on the current size, age and sex distribution of the
population and its prediction into the sixth decade were also used.
RESULTS: The prevalence of HF was 3.6% in the sexes combined, but higher in men
(5.1%) than women (2.7%) (p < .001). The prevalence of HF per age groups ≤69,
70-74, 75-79, 80-84 and ≥85 years was 1.7%, 1.5%, 3.7%, 5.2% and 7.2%,
respectively. The number of individuals ≥70 years with HF will increase
considerably in the future. Thus, a calculation based on the projected age
distribution and increase in the number of elderly ≥70 years in the coming
decades, demonstrated that the number of patients with HF will have increased
2.3-fold by the year 2040 and tripled by the year 2060.
CONCLUSIONS: This study, in a cohort of elderly participants representative of
the general population in a Nordic country, predicts that HF will be a major and
increasing health problem in the coming decades.
DOI: 10.1080/14017431.2017.1311023
PMCID: PMC5681737
213. Lancet Diabetes Endocrinol. 2018 Mar;6(3):208-222. doi:
10.1016/S2213-8587(17)30432-1. Epub 2018 Jan 19.
Prevalence of obesity, hypertension, and diabetes, and cascade of care in
sub-Saharan Africa: a cross-sectional, population-based study in rural and urban
Malawi.
Price AJ(1), Crampin AC(2), Amberbir A(3), Kayuni-Chihana N(4), Musicha C(4),
Tafatatha T(4), Branson K(5), Lawlor DA(6), Mwaiyeghele E(4), Nkhwazi L(4),
Smeeth L(7), Pearce N(7), Munthali E(4), Mwagomba BM(8), Mwansambo C(9), Glynn
JR(5), Jaffar S(10), Nyirenda M(2).
Author information:
(1)Department of Infectious Disease Epidemiology, London School of Hygiene &
Tropical Medicine, London, UK; Malawi Epidemiology and Intervention Research
Unit, Lilongwe and Karonga, Malawi. Electronic address: alison.price@lshtm.ac.uk.
Tropical Medicine, London, UK; Malawi Epidemiology and Intervention Research
Unit, Lilongwe and Karonga, Malawi.
(3)Medical and Research Department, Dignitas International, Zomba, Malawi.
(4)Malawi Epidemiology and Intervention Research Unit, Lilongwe and Karonga,
Malawi.
(6)MRC Integrated Epidemiology Unit and School of Social and Community
Epidemiology Medicine, University of Bristol, Bristol, UK.
(7)Department of Non-Communicable Disease Epidemiology, London School of Hygiene

& Tropical Medicine, London, UK.
(8)Global Health Implementation Program, School of Public Health and Family
Medicine, College of Medicine, Blantyre, Malawi; Lighthouse Trust, Kamuzu Central
Hospital, Lilongwe, Malawi.
(9)Ministry of Health, Lilongwe, Malawi.
(10)Department of International Public Health, Liverpool School of Tropical
Medicine, Liverpool, UK.
Comment in
Lancet Diabetes Endocrinol. 2018 Mar;6(3):163-164.
BACKGROUND: Sub-Saharan Africa is in rapid demographic transition, and
non-communicable diseases are increasingly important causes of morbidity and
mortality. We investigated the burden of diabetes, overweight and obesity,
hypertension, and multimorbidity, their treatment, and their associations with
lifestyle and other factors in Malawi, a very poor country with a predominantly
rural-but rapidly growing urban-population, to identify high-risk populations and
inform appropriate interventions.
METHODS: In this cross-sectional, population-based study, we enrolled all adults
(≥18 years) residing in two defined geographical areas within Karonga District
and Lilongwe city. All adults self-defining as usually resident in the study
areas were eligible, and recruited at household level. Participants were
interviewed, had anthropometry and blood pressure measured, and had fasting blood
samples collected. The study outcomes were prevalence estimates and risk ratios
for diabetes (defined as fasting blood glucose of at least 7·0 mmol/L or
self-report of a previous diagnosis of diabetes), hypertension (systolic blood
pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or
self-report of current antihypertensive medication), overweight (BMI of 25·0-29·9
kg/m2) and obesity (BMI of 30·0 kg/m2 or more), and multimorbidity (two or more
of the above conditions) by location-specific (urban vs rural), age-specific, and
sex-specific groups, calculated using negative binomial regression. We used χ2

likelihood ratio tests to assess heterogeneity by age, location, and sex.
FINDINGS: Between May 16, 2013, and Feb 8, 2016, we enrolled 15 013 (62%) of
24 367 eligible urban adults in Lilongwe and 13 878 (88%) of 15 806 eligible
rural adults in Karonga District. Overweight and obesity, hypertension, and
diabetes were highly prevalent, more so in urban residents, the less poor, and
better educated than in rural, the poorest, and least educated participants. 18%
of urban men (961 of 5211 participants) and 44% (4115 of 9282) of urban women,
and 9% (521 of 5834) of rural men and 27% (2038 of 7497) of rural women were
overweight or obese; 16% (859 of 5212), 14% (1349 of 9793), 13% (787 of 5847),
and 14% (1101 of 8025) had hypertension; and 3% (133 of 3928), 3% (225 of 7867),
2% (84 of 5004), and 2% (124 of 7116) had diabetes, respectively. Of 566
participants with diabetes, 233 (41%) were undiagnosed, and of 4096 participants
with hypertension, 2388 (58%) were undiagnosed. Fewer than half the participants
on medication for diabetes or hypertension had well controlled diabetes (84 [41%]
of 207 participants) or blood pressure (440 [37%] of 1183 participants).
Multimorbidity was highest in urban women (n=519, 7%).
INTERPRETATION: Overweight and obesity, hypertension, and diabetes are highly
prevalent in urban and rural Malawi, yet many patients are undiagnosed and
management is limited. Local-evidence-informed multisectoral, innovative, and
targeted interventions are needed urgently to manage the already high burden.
FUNDING: Wellcome Trust.
article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights
reserved.
DOI: 10.1016/S2213-8587(17)30432-1
PMCID: PMC5835666

eCollection 2017.
The Prevalence of Self-Reported Diabetes in the Australian National Eye Health
Survey.
Keel S(1), Foreman J(1)(2), Xie J(1), van Wijngaarden P(1)(2), Taylor HR(3),
Dirani M(1).
Author information:
(1)Centre for Eye Research Australia, Royal Victorian Eye & Ear Hospital,
Melbourne, Australia.
(2)Ophthalmology, University of Melbourne, Department of Surgery, Melbourne,
Australia.
(3)Indigenous Eye Health Unit, Melbourne School of Population and Global Health,
The University of Melbourne, Melbourne, Australia.
OBJECTIVE: To present the prevalence of self-reported diabetes in Indigenous and
non-Indigenous participants in the National Eye Health Survey.
RESEARCH DESIGN AND METHODS: 3098 non-Indigenous Australians aged 50-98 years and
1738 Indigenous Australians aged 40-92 years were examined in 30 randomly
selected sites, stratified by remoteness. A history of diabetes was obtained
using an interviewer-administered questionnaire.
RESULTS: 13.91% (431/3098) of non-Indigenous Australians and 37.11% (645/1738) of
Indigenous Australians had self-reported diabetes. The age-adjusted prevalence of
self-reported diabetes for non-Indigenous and Indigenous Australians was 11.49%
and 43.77%, respectively (p <0.001). The prevalence of self-reported diabetes
increased markedly with age (OR = 1.04 per year, p = 0.017). Indigenous
Australians living in very remote areas were more likely to have self-reported
diabetes than those in major city areas (OR = 1.61, p = 0.038).
CONCLUSIONS: The prevalence of self-reported diabetes in Australia was high, with

the prevalence being almost 4 times higher in Indigenous Australians compared
with non-Indigenous Australians. With the prevalence of diabetes likely to
increase, the results of this national survey may inform future policy, planning
and funding allocation to assist in controlling the diabetes epidemic.
PMCID: PMC5207759
Conflict of interest statement: The National Eye Health Survey received funding
from a commercial source, Novartis Pharmaceuticals. This does not alter our
adherence to PLOS ONE policies on sharing data and materials.
215. BMJ Open. 2016 Dec 13;6(12):e012255. doi: 10.1136/bmjopen-2016-012255.
Prevalence of type 2 diabetes mellitus in women of childbearing age in Africa
during 2000-2016: protocol of a systematic review and meta-analysis.
Chivese T(1)(2), Mahmoud W(1), Magodoro I(3), Kengne AP(4), Norris SA(2), Levitt
NS(5).
Author information:
(1)Chronic Disease Initiative for Africa, Department of Medicine, University of
Cape Town, South Africa.
(2)Faculty of Health Sciences, South Africa Medical Research Council
Developmental Pathways for Health Research Unit, Department of Paediatrics,
University of the Witwatersrand, Johannesburg, South Africa.
(3)Harvard Medical School, Boston, USA.
(4)Non-communicable Disease Research Unit, South African Medical Research
Council, Cape Town, South Africa.

(5)Division of Endocrinology, Department of Medicine, University of Cape Town,
Cape Town, South Africa.
INTRODUCTION: African women of childbearing age are increasingly being exposed to
risk factors for type 2 diabetes mellitus (T2DM), most particularly obesity. A
differentiating feature of diabetes in women of childbearing age is that the
disease may affect the mother and the developing fetus. Apart from mapping the
extent of the problem, understanding the prevalence of T2DM in African women of
childbearing age can help to galvanise targeted interventions for reducing the
burden of T2DM. This is a protocol for a systematic review aiming to assess the
prevalence of and risk factors for T2DM in women of childbearing age
(15-49 years) in Africa.
METHODS AND ANALYSES: We will carry out a comprehensive literature search among a
number of databases, using appropriate adaptations of the African search filter
to identify diabetes prevalence studies, published from 2000 to 2016, among
African women of childbearing age (15-49 years) according to the WHO definition.
Full copies of articles identified through searches and considered to meet the
inclusion criteria will be obtained for data extraction and synthesis. The
analysis of the primary outcome (prevalent diabetes) will include two steps: (1)
identification of data sources and documenting estimates and (2) application of
the random-effects meta-analysis model to aggregate prevalence estimates and
account for between-study variability in calculating the overall pooled estimates
and 95% CI for diabetes prevalence. We will assess heterogeneity and publication
bias using established methods. This systematic review will be reported according
to the Preferred Reporting Items for Systematic reviews and Meta-Analyses
Protocol (PRISMA-P) 2015.
ETHICS AND DISSEMINATION: Ethical approval is not required for this study, given
that this is a protocol for a systematic review, which utilises published data.
The findings of this study will be widely disseminated through peer reviewed
publications and conference presentations.
TRIAL REGISTRATION NUMBER: CRD42015027635.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/.
DOI: 10.1136/bmjopen-2016-012255
PMCID: PMC5168695
216. Front Psychol. 2016 Aug 10;7:1136. doi: 10.3389/fpsyg.2016.01136. eCollection
2016.
PREVIEW Behavior Modification Intervention Toolbox (PREMIT): A Study Protocol for
a Psychological Element of a Multicenter Project.
Kahlert D(1), Unyi-Reicherz A(2), Stratton G(3), Meinert Larsen T(4), Fogelholm
M(5), Raben A(4), Schlicht W(2).
Author information:
(1)Division Exercise and Sports, University of Education Schwäbisch Gmünd
Schwäbisch Gmünd, Germany.
(2)Chair Exercise and Health Science, Stuttgart Research Initiative Human Factors
in Ageing, Technology, and Environment, University of Stuttgart Stuttgart,
Germany.
(3)Applied Sport, Technology, Exercise and Medicine Research Centre, Swansea
University Swansea, UK.
(4)Department of Nutrition, Exercise, and Sports, University of Copenhagen
Copenhagen, Denmark.
(5)Department of Food and Environmental Science, University of Helsinki Helsinki,
Finland.
BACKGROUND: Losing excess body weight and preventing weight regain by changing
lifestyle is a challenging but promising task to prevent the incidence of type-2
diabetes. To be successful, it is necessary to use evidence-based and
theory-driven interventions, which also contribute to the science of behavior
modification by providing a deeper understanding of successful intervention
components.
OBJECTIVE: To develop a physical activity and dietary behavior modification
intervention toolbox (PREMIT) that fulfills current requirements of being
theory-driven and evidence-based, comprehensively described and feasible to
evaluate. PREMIT is part of an intervention trial, which aims to prevent the
onset of type-2 diabetes in pre-diabetics in eight clinical centers across the
world by guiding them in changing their physical activity and dietary behavior
through a group counseling approach.
METHODS: The program development took five progressive steps, in line with the
Public Health Action Cycle: (1) Summing-up the intervention goal(s), target group
and the setting, (2) uncovering the generative psychological mechanisms, (3)
identifying behavior change techniques and tools, (4) preparing for evaluation
and (5) implementing the intervention and assuring quality.
RESULTS: PREMIT is based on a trans-theoretical approach referring to valid
behavior modification theories, models and approaches. A major "product" of
PREMIT is a matrix, constructed for use by onsite-instructors. The matrix
includes objectives, tasks and activities ordered by periods. PREMIT is
constructed to help instructors guide participants' behavior change. To ensure
high fidelity and adherence of program-implementation across the eight
intervention centers standardized operational procedures were defined and
"train-the-trainer" workshops were held. In summary PREMIT is a theory-driven,
evidence-based program carefully developed to change physical activity and
dietary behaviors in pre-diabetic people.

DOI: 10.3389/fpsyg.2016.01136
PMCID: PMC4978707
PMID: 27559319
217. Sci Rep. 2017 Sep 21;7(1):12115. doi: 10.1038/s41598-017-12535-9.
Probiotic reduces bacterial translocation in type 2 diabetes mellitus: A
randomised controlled study.
Sato J(1), Kanazawa A(2)(3), Azuma K(1), Ikeda F(1), Goto H(1), Komiya K(1),
Kanno R(1), Tamura Y(1)(4), Asahara T(5)(6), Takahashi T(5)(6), Nomoto K(5)(6),
Yamashiro Y(5), Watada H(1)(7)(8)(4).
Author information:
of Medicine, Tokyo, 113-8421, Japan.
of Medicine, Tokyo, 113-8421, Japan. akana@juntendo.ac.jp.
(3)Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate
School of Medicine, Tokyo, 113-8421, Japan. akana@juntendo.ac.jp.
(4)Sportology Center, Juntendo University Graduate School of Medicine, Tokyo,
113-8421, Japan.
(5)Probiotics Research Laboratory, Juntendo University Graduate School of
Medicine, Tokyo, 113-8421, Japan.
(6)Yakult Central Institute, Tokyo, 186-8650, Japan.
(7)Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate
School of Medicine, Tokyo, 113-8421, Japan.
(8)Center for Identification of Diabetic Therapeutic Targets, Juntendo University
Graduate School of Medicine, Tokyo, 113-8421, Japan.

Gut bacterial translocation to the blood may play an important role in the
development of insulin resistance in type 2 diabetes. Here, we performed an
interventional randomised control study to investigate whether probiotics could
reduce bacterial translocation and cause changes in the gut microbiota. Seventy
Japanese patients with type 2 diabetes were randomised to two groups: the
probiotic group drank Lactobacillus casei strain Shirota-fermented milk, while
the control group ingested no probiotics. The trial was conducted for 16 weeks.
At baseline, 8 and 16 weeks, the gut microbiota composition in feces and blood,
fecal organic acids, and other biochemical parameters were measured. At the end
of the study, the fecal counts of the Clostridium coccoides group and Clostridium
leptum subgroup in the probiotic group were significantly higher than in the
control group. As expected, the fecal counts of total Lactobacillus were
significantly higher in the probiotic group. Intriguingly, the total count of
blood bacteria was significantly lower in the probiotic group. However, fecal
organic acids were comparable between the two groups. Our results showed that
probiotic administration reduced bacterial translocation and altered the gut
microbiota in Japanese patients with type 2 diabetes mellitus.
DOI: 10.1038/s41598-017-12535-9
PMCID: PMC5608749
PMID: 28935921
218. Health Qual Life Outcomes. 2017 Jul 14;15(1):142. doi: 10.1186/s12955-017-0717-6.
Profile and predictors of health related quality of life among type II diabetes
mellitus patients in Quetta city, Pakistan.
Iqbal Q(1), Ul Haq N(1), Bashir S(2), Bashaar M(3).

Author information:
(1)Faculty of Pharmacy & Health Sciences, University of Baluchistan, Quetta,
Pakistan.
(2)Faculty of Pharmacy, University of Sargodha, Punjab, Pakistan.
(3)SMART Afghan International Trainings & Consultancy, Kabul, Afghanistan.
mohammad.bashaar@yahoo.com.
BACKGROUND: This study aims to assess the profile and predictors of
Health-Related Quality of Life (HRQoL) in Type II Diabetes Mellitus (T2DM)
patients in Quetta, Pakistan.
METHODS: The study was designed as a questionnaire based, cross sectional
analysis. 300 Type II diabetic patients attending public and private hospitals
were targeted for data collection. In addition to demographic and disease related
information, Euroqol Quality of Life was used to measure HRQoL. Moreover, Drug
Attitude Inventory and Michigan Diabetes Knowledge Test were used to assess
medication adherence and diabetes related knowledge respectively. Treatment
satisfaction was assessed by patient's experience towards health care
professionals and available facilities. Descriptive statistics were used to
elaborate patients' demographic and disease related characteristics. Binary
logistic regression was used to predict factors independently associated with
HRQoL. SPSS v. 20 was used for data analysis and p < 0.05 was taken as
significant.
RESULTS: Patients in the current study reported poor HRQoL with a mean score of
0.48 ± 0.36. Age, duration of disease, number of prescribed drugs, medication
adherence and treatment satisfaction were significantly associated (p < 0.05)
with HRQoL in the cross tabulation analysis. The significant variables were
entered into the model that showed significant goodness of fit with highly
significant Omnibus Test of Model Coefficient (Chi-square = 12.983, p = 0.030,
df = 4). Medication adherence was reported as a significant predictor of HRQoL
with an increase of one adherence score was associated with improvement of HRQoL
by a factor of 1.75 provided other variables remain constant.

CONCLUSION: The study presents a model that is associated with HRQoL with patient
with T2DM, where medication adherence shaped as a predictor of HRQoL. Healthcare
professionals should pay special attention on patients' medication taking
behavior and should put their efforts in explaining the benefits of the
medication adherence to the patients.
DOI: 10.1186/s12955-017-0717-6
PMCID: PMC5512812
219. Front Psychol. 2017 Dec 5;8:2063. doi: 10.3389/fpsyg.2017.02063. eCollection
2017.
Psychosocial Interventions and Wellbeing in Individuals with Diabetes Mellitus: A
Systematic Review and Meta-Analysis.
Pascoe MC(1)(2), Thompson DR(3)(4), Castle DJ(3)(5), Jenkins ZM(5), Ski CF(3)(5).
Author information:
(1)Institute of Sport, Exercise and Active Living (ISEAL), Victoria University,
Melbourne, VIC, Australia.
(2)Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
(3)Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
(4)Department of Epidemiology and Preventive Medicine, Monash University,
Melbourne, VIC, Australia.
(5)Mental Health Service, St. Vincent's Hospital, Melbourne, VIC, Australia.
Purpose: A number of studies, including systematic reviews, show beneficial
effects of psychosocial interventions for people with diabetes mellitus; however,
they have not been assessed using meta-analysis. The purpose of this
meta-analysis of randomized controlled trials is to investigate the effects of
psychosocial interventions on depressive and anxiety symptoms, quality of life
and self-efficacy in individuals with diabetes mellitus. Methods: The databases
Pubmed, MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science and SocINDEX were
searched with no year restriction. Eligible studies were randomized controlled
trials published in English that included individuals diagnosed with diabetes
mellitus, aged 18 years or above, who engaged in a psychosocial intervention,
with outcome measures addressing depressive or anxiety symptomology, quality of
life or self-efficacy. Eligible studies needed to compare the intervention to
usual care. Study selection was completed using Covidence and meta-analysis was
undertaken using Comprehensive Meta-Analysis software. Results: Seven studies
were included in the meta-analysis. Five studies investigated the effects of
psychosocial interventions and showed a medium to large benefit for depressive
symptoms (SMD: -0.70; CI: -1.27, -0.13) which persisted at follow up (SMD: -1.54,
CI: -2.97, -0.12). Similar results were not seen immediately post-intervention in
the three studies that assessed anxiety symptoms (SMD: -0.30; CI: -0.69, 0.10);
however, a medium beneficial effect was seen at follow up (SMD = -0.61, CI =
-0.92 to -0.31). Small benefits were seen in the three studies assessing quality
of life outcomes (SMD: 0.30, CI: 0.06, 0.55). No benefit was seen in the two
studies assessing self-efficacy (SMD: 0.23, CI: -0.11, 0.57). Conclusions: The
results of the current study provide preliminary evidence that psychosocial
interventions, compared to usual care, reduce depressive symptoms, and may
improve quality of life in individuals with diabetes. However, only a few studies
were included and the clinical significance of these findings is unknown.
DOI: 10.3389/fpsyg.2017.02063
PMCID: PMC5723413
PMID: 29259563
220. Eur Radiol. 2018 Mar;28(3):1037-1045. doi: 10.1007/s00330-017-5080-9. Epub 2017

Oct 10.
Rapid volumetric photoacoustic tomographic imaging with a Fabry-Perot ultrasound
sensor depicts peripheral arteries and microvascular vasomotor responses to
thermal stimuli.
Plumb AA(1), Huynh NT(2), Guggenheim J(2), Zhang E(2), Beard P(2).
Author information:
(1)Centre for Medical Imaging, Division of Medicine, University College London,
Podium Level 2, 235 Euston Road, London, NW1 2BU, UK. andrew.plumb@nhs.net.
(2)Photoacoustic Imaging Group, Department of Medical Physics and Biomedical
Engineering, University College London, London, UK.
PURPOSE: To determine if a new photoacoustic imaging (PAI) system successfully
depicts (1) peripheral arteries and (2) microvascular circulatory changes in
response to thermal stimuli.
METHODS: Following ethical permission, 8 consenting subjects underwent PAI of the
dorsalis pedis (DP) artery, and 13 completed PAI of the index fingertip. Finger
images were obtained after immersion in warm (30-35 °C) or cold (10-15 °C) water
to promote vasodilation or vasoconstriction. The PAI instrument used a
Fabry-Perot interferometeric ultrasound sensor and a 30-Hz 750-nm pulsed
excitation laser. Volumetric images were acquired through a 14 × 14 × 14-mm
volume over 90 s. Images were evaluated subjectively and quantitatively to
determine if PAI could depict cold-induced vasoconstriction. The full width at
half maximum (FWHM) of resolvable vessels was measured.
RESULTS: Fingertip vessels were visible in all participants, with mean FWHM of
125 μm. Two radiologists used PAI to correctly identify vasoconstricted fingertip
capillary beds with 100% accuracy (95% CI 77.2-100.0%, p < 0.001). The number of
voxels exhibiting vascular signal was significantly smaller after cold water
immersion (cold: 5263 voxels; warm: 363,470 voxels, p < 0.001). The DP artery was
visible in 7/8 participants (87.5%).
CONCLUSION: PAI achieves rapid, volumetric, high-resolution imaging of peripheral
limb vessels and the microvasculature and is responsive to vasomotor changes
induced by thermal stimuli.
KEY POINTS: • Fabry-Perot interferometer-based photoacoustic imaging (PAI)
generates volumetric, high-resolution images of the peripheral vasculature. • The
system reliably detects thermally induced peripheral vasoconstriction (100%
correct identification rate, p < 0.001). • Vessels measuring less than 100 μm in
diameter can be depicted in vivo.
DOI: 10.1007/s00330-017-5080-9
PMCID: PMC5811589
221. J Diabetes Investig. 2018 Sep;9(5):1060-1066. doi: 10.1111/jdi.12820. Epub 2018
Mar 23.
Relationship between social engagement and diabetes incidence in a middle-aged
population: Results from a longitudinal nationwide survey in Japan.
Shibayama T(1), Noguchi H(2), Takahashi H(3), Tamiya N(1).
Author information:
(1)Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
(2)Faculty of Political Science and Economics, Waseda University, Tokyo, Japan.
(3)National Institute of Public Health, Saitama, Japan.
AIMS/INTRODUCTION: Social engagement can positively affect health status, but its
effect on diabetes incidence remains unclear. The present study aimed to assess
the relationship between social engagement and diabetes incidence in a

middle-aged Japanese population.
MATERIALS AND METHODS: We analyzed data on 31,615 people aged 50-59 years from a
prospective national survey carried out in Japan from 2005 to 2013. Diabetes
incidence was measured by asking respondents annually whether they had been
diagnosed with diabetes by a physician in the previous year. We used the
complementary log-log model for interval-censored survival time analysis. Social
engagement was assessed at baseline as participation in social activities, having
the companionship of friends, living with someone and employment status.
Covariates including sex, age, health status and health behaviors were also
measured at baseline.
RESULTS: After adjusting for covariates measured at baseline, the effect size of
social engagement on diabetes incidence was the same as or larger than that of
the covariates. Respondents who participated in social activities (hazard ratio
[HR] 0.89, 95% confidence interval [CI] 0.87-0.92), had the companionship of
friends (HR 0.97, 95% CI: 0.95-1.00), lived with someone (HR 0.85, 95% CI:
0.82-0.89) and were employed (HR 0.94, 95% CI: 0.92-0.96) were significantly less
vulnerable to diabetes than were those who did not.
CONCLUSIONS: The present study found a prospective association between social
engagement and diabetes incidence among a middle-aged population. Future
strategies to prevent diabetes in Japan should focus on both social and personal
factors.
© 2018 The Authors. Journal of Diabetes Investigation published by Asian
Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia,
Ltd.
DOI: 10.1111/jdi.12820
PMCID: PMC6123021
PMID: 29430865
222. PLoS One. 2017 Nov 30;12(11):e0188650. doi: 10.1371/journal.pone.0188650.
eCollection 2017.
Relative muscle mass and the risk of incident type 2 diabetes: A cohort study.
Hong S(1), Chang Y(1)(2)(3), Jung HS(1), Yun KE(1), Shin H(1)(4), Ryu S(1)(2)(3).
Author information:
(1)Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital,
Sungkyunkwan University School of Medicine, Seoul, Korea.
(2)Department of Occupational and Environmental Medicine, Kangbuk Samsung
Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
(3)Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan
University, Seoul, Korea.
(4)Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan
University School of Medicine, Seoul, Korea.
AIMS: The association between relative muscle mass (RMM) and incidence of type 2
diabetes (T2DM) is largely unknown. We examined whether RMM predicted development
of T2DM in an apparently young healthy population.
METHODS: This cohort study was comprised of 113,913 men and 89,854 women, free of
T2DM at baseline, who underwent a health checkup examination and were followed-up
annually or biennially for an average of 2.9 years. We used skeletal muscle mass
index (SMI) as an indicator of RMM. SMI (%) [total skeletal muscle mass (kg)/body
weight (kg)×100] was estimated using a bioelectrical impedance analyzer. The
study outcome was incident T2DM, defined as fasting serum glucose ≥126 mg/dL,
HbA1C ≥6.5%, or use of medication for T2DM.
RESULTS: During 589,098.8 person-years of follow-up, 4,264 individuals developed
T2DM (incidence rate, 7.2 per 1000 person-years). Median age (range) at baseline
was 39.1 years (18.1-87.1). RMM was negatively associated with incidence of T2DM
in a dose-response manner. The multivariate-adjusted hazard ratios (95% CIs) for

incident T2DM comparing quartiles 3, 2 and 1 of RMM to the highest quartile were
1.32 (1.14-1.52), 1.63 (1.42-1.86), and 2.21 (1.94-2.51), respectively, for males
and 1.18 (0.88-1.58), 1.46 (1.11-1.91), and 1.96 (01.51-2.53) for females (P for
trend <0.001; 0.011). This association was stronger in younger or premenopausal
subjects.
CONCLUSIONS: RMM was negatively associated with development of T2DM in a large
sample of young and middle-aged Korean adults. Further research is required to
determine whether preservation of muscle mass through intervention affects the
risk of T2DM.
PMCID: PMC5708784
223. Cardiovasc Diabetol. 2016 Sep 9;15(1):130. doi: 10.1186/s12933-016-0444-z.
Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy:
the case for repeat application as a novel therapy for lower extremity
ulceration.
Epps JA(1), Smart NA(2).
Author information:
(1)School of Science and Technology, The University of New England, Armidale,
NSW, 2351, Australia.
(2)School of Science and Technology, The University of New England, Armidale,
NSW, 2351, Australia. nsmart2@une.edu.au.
An emerging treatment modality for reducing damage caused by
ischaemia-reperfusion injury is ischaemic conditioning. This technique induces

short periods of ischaemia that have been found to protect against a more
significant ischaemic insult. Remote ischaemic conditioning (RIC) can be
administered more conveniently and safely, by inflation of a pneumatic blood
pressure cuff to a suprasystolic pressure on a limb. Protection is then
transferred to a remote organ via humoral and neural pathways. The diabetic state
is particularly vulnerable to ischaemia-reperfusion injury, and ischaemia is a
significant cause of many diabetic complications, including the diabetic foot.
Despite this, studies utilising ischaemic conditioning and RIC in type 2 diabetes
have often been disappointing. A newer strategy, repeat RIC, involves the
repeated application of short periods of limb ischaemia over days or weeks. It
has been demonstrated that this improves endothelial function, skin
microcirculation, and modulates the systemic inflammatory response. Repeat RIC
was recently shown to be beneficial for healing in lower extremity diabetic
ulcers. This article summarises the mechanisms of RIC, and the impact that type 2
diabetes may have upon these, with the role of neural mechanisms in the context
of diabetic neuropathy a focus. Repeat RIC may show more promise than RIC in type
2 diabetes, and its potential mechanisms and applications will also be explored.
Considering the high costs, rates of chronicity and serious complications
resulting from diabetic lower extremity ulceration, repeat RIC has the potential
to be an effective novel advanced therapy for this condition.
DOI: 10.1186/s12933-016-0444-z
PMCID: PMC5018170
224. Front Pharmacol. 2017 Nov 15;8:835. doi: 10.3389/fphar.2017.00835. eCollection
2017.
Renoprotective Effect of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type
2 Diabetes Mellitus.
Esaki H(1)(2), Tachi T(1)(3), Goto C(3), Sugita I(1), Kanematsu Y(1), Yoshida
A(1), Saito K(1), Noguchi Y(1), Ohno Y(3), Aoyama S(3), Yasuda M(3), Mizui T(3),
Yamamura M(2), Teramachi H(1)(4).
Author information:
(1)Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan.
(2)Department of Pharmacy, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
(3)Department of Pharmacy, Gifu Municipal Hospital, Gifu, Japan.
(4)Laboratory of Community Healthcare Pharmacy, Gifu Pharmaceutical University,
Gifu, Japan.
Diabetic nephropathy is one of three major complications of diabetes mellitus,
often leading to chronic renal failure requiring dialysis. Recently developed
dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit renoprotective effects in
addition to antihyperglycemic effects. In this study, we retrospectively
investigated temporal changes in the renal function index of patients with type 2
diabetes mellitus (DM) and examined the influence of DPP-4 inhibitors on renal
function. Patients with type 2 DM (>18 years old) prescribed hypoglycemic agents
at Gifu Municipal Hospital for ≥3 months between March 2010 and April 2014 were
included in the study. Renal function was evaluated as estimated the decline in
12-month glomerular filtration rate from the baseline in patients receiving and
not receiving DPP-4 inhibitors. Patient data from the DPP-4 inhibitor-treated
(501 patients, 58.6%) and untreated (354, 41.4%) groups were analyzed using
multiple logistic regression analysis, as well as Cox proportional-hazards
regression analysis (616, 55.6% and 491, 44.4%, for DPP-4 inhibitors-treated and
untreated groups). Multiple logistic regression analysis indicated that DPP-4
inhibitors significantly lowered the estimated glomerular filtration rate (eGFR)
decline [20% over 12 months; odds ratio (OR), 0.626; 95% confidence interval
[CI], 0.409-0.958; P = 0.031]. Similar results were obtained using Cox
proportional-hazards regression analysis (hazard ratio [HR], 0.707; 95% CI,

0.572-0.874; P = 0.001). These findings suggest that DPP-4 inhibitors suppress
the decrease of estimated glomerular filtration rate in patients with type 2 DM
and show a renoprotective effect.
DOI: 10.3389/fphar.2017.00835
PMCID: PMC5694778
PMID: 29187821
225. World J Diabetes. 2018 Jul 15;9(7):127-131. doi: 10.4239/wjd.v9.i7.127.
Reversibility of diabetes mellitus: Narrative review of the evidence.
Ang GY(1).
Author information:
(1)Health Services and Outcomes Research, National Healthcare Group, Singapore
138543, Singapore. gary_ang@nhg.com.sg.
The global disease burden of diabetes mellitus is high. It is well-established
that prediabetes is reversible but it is unclear whether diabetes is reversible
once it has been diagnosed. The objective of this narrative review is to review
the evidence of reversibility of diabetes mellitus and stimulate interest in
prolonged remission as a treatment target. The current evidence for bariatric
surgery is stronger than intensive medical management and the evidence is
stronger for type 2 diabetes patients compared with type 1 diabetes patients. It
is also unclear whether non obese diabetes patients would benefit from such
interventions and the duration of diabetes before diabetes become irreversible.
Further research is needed in this area especially with regards to the subgroup
of diabetes patient who will benefit from these interventions and the long term
safety and efficacy remains unknown especially with intensive medical management.
DOI: 10.4239/wjd.v9.i7.127
PMCID: PMC6068740
PMID: 30079148
Conflict of interest statement: Conflict-of-interest statement: No potential
conflicts of interest.
eCollection 2018.
Risk of adverse treatment outcomes among new pulmonary TB patients co-infected
with diabetes in Pakistan: A prospective cohort study.
Mukhtar F(1)(2), Butt ZA(3)(2).
Author information:
(1)Department of Community Medicine, Lahore Medical & Dental College, Lahore,
Pakistan.
(2)Department of Epidemiology & Biostatistics, Health Services Academy,
Islamabad, Pakistan.
(3)School of Population and Public Health, University of British Columbia,
Vancouver, Canada.
PURPOSE: The escalating burden of diabetes in countries tackling high burden of
tuberculosis (TB) has adverse implications for co-infected individuals and
National TB control efforts. We aimed to study whether there was a difference in
treatment outcome among diabetic and non-diabetic pulmonary TB patients and
identify the determinants of treatment outcome among the two groups.
MATERIALS AND METHODS: This prospective cohort study recruited new patients of
pulmonary tuberculosis (PTB) aged 15 years and above who were diagnosed at and
registered with Gulab Devi Chest Hospital, Lahore, Pakistan for anti-tuberculosis
treatment (ATT). PTB patients were screened for diabetes using random and fasting
blood glucose tests. Diabetic and non-diabetic PTB patients were followed up at
second, fifth and sixth month of ATT and 6 months after ATT completion to
determine treatment outcome. Multivariate logistic regression analysis was
conducted to assess association between various factors and treatment outcome.
RESULTS: Of 614 PTB patients, (n = 113 [18%]) were diabetic and (n = 501 [82%])
non-diabetic. Final model showed that diabetics were more likely to experience an
unfavorable outcome as compared to non-diabetics (adjusted odds ratio [aOR] =
2.70, 95% Confidence Interval [CI] = 1.30 to 5.59). Other predictors of
unfavorable outcome included rural residence (aOR = 1.98, 95% CI = 1.14 to 3.47),
body mass index less than 18.50 (aOR = 1.89, 95% CI = 1.03 to 3.47) and being a
smoker (aOR = 2.03, 95%CI = 1.04 to 3.94).
CONCLUSION: Our study shows unfavorable treatment outcome among diabetic PTB
patients. Integrated models of care with screening/testing and management for
diabetes and TB could improve TB treatment outcomes.
PMCID: PMC6224090
PMID: 30408109
interests exist.
227. J Mol Endocrinol. 2018 Jul;61(1):R43-R60. doi: 10.1530/JME-18-0011. Epub 2018 Apr
16.
The role of beta cell heterogeneity in islet function and insulin release.
Nasteska D(1)(2)(3), Hodson DJ(4)(2)(3).
Author information:
(1)Institute of Metabolism and Systems Research (IMSR)University of Birmingham,
Edgbaston, UK.
(2)Centre for EndocrinologyDiabetes and Metabolism, Birmingham Health Partners,
Birmingham, UK.
(3)COMPARE University of Birmingham and University of Nottingham
MidlandsBirmingham, UK.
(4)Institute of Metabolism and Systems Research (IMSR)University of Birmingham,
Edgbaston, UK d.hodson@bham.ac.uk.
It is becoming increasingly apparent that not all insulin-secreting beta cells
are equal. Subtle differences exist at the transcriptomic and protein expression
levels, with repercussions for beta cell survival/proliferation, calcium
signalling and insulin release. Notably, beta cell heterogeneity displays
plasticity during development, metabolic stress and type 2 diabetes mellitus
(T2DM). Thus, heterogeneity or lack thereof may be an important contributor to
beta cell failure during T2DM in both rodents and humans. The present review will
discuss the molecular and cellular features of beta cell heterogeneity at both
the single-cell and islet level, explore how this influences islet function and
insulin release and look into the alterations that may occur during obesity and
T2DM.
© 2018 The authors.
DOI: 10.1530/JME-18-0011
PMCID: PMC5976077
PMID: 29661799
228. Nutrients. 2017 Oct 10;9(10). pii: E1104. doi: 10.3390/nu9101104.
Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in
Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized
Controlled Trial.
Yang L(1), Ling W(2), Yang Y(3), Chen Y(4), Tian Z(5), Du Z(6), Chen J(7), Xie
Y(8), Liu Z(9), Yang L(10).
Author information:
(1)Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department
of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080,
China. yanglp6@mail2.sysu.edu.cn.
China. lingwh@mail.sysu.edu.cn.
China. yangyan3@mail.sysu.edu.cn.
(4)Department of Medical Statistics & Epidemiology, School of Public Health, Sun
Yet-Sen University, Guangzhou 510080, China. chenyum@mail.sysu.edu.cn.
China. shishujushi@sina.com.
(6)Department of Medical Statistics & Epidemiology, School of Public Health, Sun
Yet-Sen University, Guangzhou 510080, China. duzhch3@mail2.sysu.edu.cn.
(7)BaiYun Hospital, YueXiu District, Guangzhou 510030, China. jianyc@163.com.
(8)BaiYun Hospital, YueXiu District, Guangzhou 510030, China.
xinling_3@aliyun.com.

China. liuzhm8@mail.sysu.edu.cn.
China. yangll7@mail.sysu.edu.cn.
Objective: In vitro and animal studies suggest that purified anthocyanins have
favorable effects on metabolic profiles, but clinical trials have reported
inconsistent findings. Furthermore, no study has been specifically conducted
among individuals with prediabetes. The aim of this study was to investigate
whether purified anthocyanins could improve cardiometabolic risk factors in
Chinese adults with early untreated hyperglycemia. Research Design and Methods:
This was a 12-week randomized, double-blind, placebo-controlled trial. A total of
160 participants aged 40-75 years with prediabetes or early untreated diabetes
were randomly allocated to receive either purified anthocyanins (320 mg/day, n =
80) or placebo (n = 80) of identical appearance. A three-hour oral glucose
tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated
hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and
lipids) were measured at baseline and at the end of the trial. Results: A total
of 138 subjects completed the protocol. Compared with placebo, purified
anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005),
low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04),
apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and
apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to
intention-to-treat analysis. Subgroup analyses suggested that purified
anthocyanins were more effective at improving glycemic control, insulin
sensitivity, and lipids among patients with elevated metabolic markers.
Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults
with prediabetes or early untreated diabetes indicated that purified anthocyanins
favorably affected glycemic control and lipid profile. Future studies of a longer
duration that explore the dose-response relationship among patients with
cardiometabolic disorders are needed to confirm our findings.

DOI: 10.3390/nu9101104
PMCID: PMC5691720
Conflict of interest statement: All the authors have no conflict of interest to
claim.
229. Curationis. 2018 Mar 26;41(1):e1-e8. doi: 10.4102/curationis.v41i1.1815.
The roles, training and knowledge of community health workers about diabetes and
hypertension in Khayelitsha, Cape Town.
Tsolekile LP(1), Schneider H, Puoane T.
Author information:
(1)School of Public Health, University of the Western Cape. ltsolekile@uwc.ac.za.
BACKGROUND: The current roles and capacity of community health workers (CHWs) in
the management and control of non-communicable diseases (NCDs) remain poorly
understood.
OBJECTIVES: To assess CHWs' current roles, training and knowledge about diabetes
and hypertension in Khayelitsha, Cape Town.
METHODS: A cross-sectional study of 150 CHWs from two non-governmental
organisations contracted to provide NCD care as part of a comprehensive package
of services was conducted. An interviewer-administered closed-ended questionnaire
was used to determine the roles, training, in-service support, knowledge and
presence of NCDs. Descriptive analyses of these domains and multivariate analyses
of the factors associated with CHWs' knowledge of hypertension and diabetes were
conducted.
RESULTS: The vast majority (96%) of CHWs were female, with a mean age of 35
years; 88% had some secondary schooling and 53% had been employed as CHWs for 4
years or more. Nearly half (47%) reported having an NCD. CHWs' roles in NCDs
included the delivery of medication, providing advice and physical assessment.
Only 52% of CHWs reported some formal NCD-related training, while less than half
of the trained CHWs (n = 35; 44%) had received follow-up refresher training.
CHWs' knowledge of diabetes and hypertension was poor. In the multivariate
analyses, higher knowledge scores were associated with having an NCD and
frequency of supervisory contact (≥1 per month).
CONCLUSIONS: The roles performed by CHWs are broad, varied and essential for
diabetes and hypertension management. However, basic knowledge about diabetes and
hypertension remains poor while training is unstandardised and haphazard. These
need to be improved if community-based NCD management is to be successful. The
potential of peer education as a complementary mechanism to formal training needs
as well as support and supervision in the workplace requires further exploration.
DOI: 10.4102/curationis.v41i1.1815
PMCID: PMC6091590
PMID: 29781697
230. Iran J Public Health. 2018 Jul;47(7):936-943.
Scientometric Study on Non-communicable Diseases in Iran: A Review Article.
Peykari N(1), Hashemi H(1), Asghari G(2), Ayazi M(3), Janbabaei G(4), Malekzadeh
R(5), Raeisi A(6), Sadrolsadat A(7), Asadi-Lari M(8), Farshad A(9), Farzadfar
F(10), Ghanei M(11), Haghdoost AA(12), Heshmat R(13), Jamshidi H(14), Ostovar
A(15), Takian A(16), Larijani B(1).
Author information:
(1)Iranian Non Communicable Diseases Committee (INCDC), Ministry of Health and
(2)Food and Drug Organization, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(3)Social Health Deputy, INCDC, Ministry of Health and Medical Education, Tehran,
Iran.
(4)Curative Affairs Deputy, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(5)Research and Technology Deputy, INCDC, Ministry of Health and Medical
(6)Public Health Deputy, INCDC, Ministry of Health and Medical Education, Tehran,
Iran.
(7)Development Deputy, Management, and Resources, INCDC, Ministry of Health and
(8)International Affairs, INCDC, Ministry of Health and Medical Education,
Tehran, Iran.
(9)Occupational Health Research Center, Iran University of Medical Sciences,
Tehran, Iran.
(10)Non Communicable Diseases Research Center, Endocrinology and Metabolism
Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
(11)Chemical Injuries Research Center, Baqiyatallah University of Medical
(12)Planning and Coordination Deputy, INCDC, Ministry of Health and Medical
(13)Chronic Diseases Research Center, Endocrinology and Metabolism Research
Institute, Tehran University of Medical Sciences, Tehran, Iran.
(14)Dept. of Pharmacology, School of Medicine, Shahid Beheshti University of
(15)Osteoporosis Research Center, Endocrinology and Metabolism Research
Institute, Tehran University of Medical Sciences, Tehran, Iran.
(16)Health Equity Research Center, Tehran University of Medical Sciences, Tehran,

Iran.
Background: Non-Communicable disease (NCDs) is a killer of people that needs to
urgent actions across the world. Scientific evidence is the critical arm for
effective interventions. Therefore, we aimed to quantify the trend of four main
NCDs' scientific publication in a 17-yr period, and reflect international
collaboration.
Methods: This scientometric study on four main NCDs; cardiovascular diseases,
cancers, diabetes, and chronic respiratory diseases were carried out through the
narrative review in international databases of Scopus from 2000 to 2016. In this
way, the number of articles, citations, and international collaboration were
assessed, and the frequently used terms on noncommunicable diseases were mapped
by VOSviewer software.
Results: Over the 17 years, 25827 articles about four main NCDs by Iran indexed
in Scopus have increasing trend steadily. However, chronic obstructive
respiratory publications have slow trend. The number of articles, citations, and
h index of cancer-related publications was higher than the others. Diabetes,
cardiovascular diseases, and chronic respiratory diseases scientometrics
indicators state in next positions, respectively. The most collaborative country
was USA in the four areas, and there was not seen region countries' collaboration
in top ten levels. The frequently used terms in NCDs' articles in order were
diabetes, cardiovascular diseases, and breast cancer.
Conclusion: Iran provides appropriate face of cancer, diabetes, and
cardiovascular diseases publications in the mirror of NCDs' scientometry.
However, there is need for more effort in chronic respiratory diseases
researches, and strengthen collaboration with regional countries.
PMCID: PMC6119576
PMID: 30181990
Conflict of interest statement: Conflict of Interest The authors declare that
there is no conflict of interest.
231. Cardiovasc Diabetol. 2017 Aug 10;16(1):101. doi: 10.1186/s12933-017-0585-8.
Selenoprotein S: a therapeutic target for diabetes and macroangiopathy?
Yu SS(1), Du JL(2).
Author information:
(1)Department of Endocrinology, The First Affiliated Hospital of Dalian Medical
University, Dalian, 116011, Liaoning, China.
(2)Department of Endocrinology, The First Affiliated Hospital of Dalian Medical
University, Dalian, 116011, Liaoning, China. dujianlingcn@163.com.
Inflammatory response, oxidative stress, and endoplasmic reticulum (ER) stress
are important pathophysiological bases of the occurrence and development of
diabetes mellitus (DM) and macroangiopathy complications. Selenoprotein S
(SELENOS) is involved in the regulation of these mechanisms; therefore, its
association with DM and macroangiopathy has gradually received attention from
scholars worldwide. SELENOS has different biological functions in different
tissues and organs: it exerts antioxidant protection and has anti-ER stress
effects in the pancreas and blood vessels, while it promotes the occurrence and
development of insulin resistance in the liver, adipose tissue, and skeletal
muscle. In addition, studies have confirmed that some SELENOS gene polymorphisms
can influence the inflammatory response and are closely associated with the risk
for developing DM and macroangiopathy. Therefore, comprehensive understanding of
the association between SELENOS and inflammation, oxidative stress, and ER stress
may better elucidate and supplement the pathogenic mechanisms of DM and
macroangiopathy complications. Furthermore, in-depth investigation of the

association of SELENOS function in different tissues and organs with DM and
macroangiopathy may facilitate the development of new strategies for the
prevention and treatment of DM and macrovascular complications. Here, we
summarize the consensus and controversy regarding functions of SELENOS on
currently available evidence.
DOI: 10.1186/s12933-017-0585-8
PMCID: PMC5553675
232. Nat Biomed Eng. 2017 Jan;1(1):0005. doi: 10.1038/s41551-016-0005. Epub 2016 Dec
19.
Self-adjusting synthetic gene circuit for correcting insulin resistance.
Ye H(#)(1)(2), Xie M(#)(1), Xue S(2), Charpin-El Hamri G(3), Yin J(2), Zulewski
H(1)(4), Fussenegger M(1)(5).
Author information:
26, CH-4058 Basel, Switzerland.
(2)Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical
Sciences and School of Life Sciences, East China Normal University, Dongchuan
Road 500, 200241 Shanghai, China.
(3)Institut Universitaire de Technologie, IUT, Département Génie Biologique,
F-69622 Villeurbanne Cedex, France.
(4)Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel,
Petersgraben 4, CH-4031 Basel, Switzerland.
(5)University of Basel, Faculty of Science, Mattenstrasse 26, CH-4058 Basel,
Switzerland.
By using tools from synthetic biology, sophisticated genetic devices can be
assembled to reprogram mammalian cell activities. Here, we demonstrate that a
self-adjusting synthetic gene circuit can be designed to sense and reverse the
insulin-resistance syndrome in different mouse models. By functionally rewiring
the mitogen-activated protein kinase (MAPK) signalling pathway to produce
MAPK-mediated activation of the hybrid transcription factor TetR-ELK1, we
assembled a synthetic insulin-sensitive transcription-control device that
self-sufficiently distinguished between physiological and increased blood insulin
levels and correspondingly fine-tuned the reversible expression of therapeutic
transgenes from synthetic TetR-ELK1-specific promoters. In acute experimental
hyperinsulinemia, the synthetic insulin-sensing designer circuit reversed the
insulin-resistance syndrome by coordinating expression of the insulin-sensitizing
compound adiponectin. Engineering synthetic gene circuits to sense pathologic
markers and coordinate the expression of therapeutic transgenes may provide
opportunities for future gene- and cell-based treatments of multifactorial
metabolic disorders.
DOI: 10.1038/s41551-016-0005
PMCID: PMC5412959
PMID: 28480128
Conflict of interest statement: Competing financial interests The authors declare
no competing financial interests.
233. BMC Pregnancy Childbirth. 2017 Jan 10;17(1):20. doi: 10.1186/s12884-016-1218-z.
Self-reported diabetes during pregnancy in the South African National Health and
Nutrition Examination Survey: extent and social determinants.

Chola L(1)(2), Mutyambizi C(3), Sewpaul R(3), Parker WA(3), Mchiza Z(3),
Labadarios D(3), Hongoro C(3).
Author information:
Council, HSRC Building, 134 Pretorius Street, Pretoria, 0002, South Africa.
LChola@hsrc.ac.za.
(2)School of Public Health, Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, South Africa. LChola@hsrc.ac.za.
Council, HSRC Building, 134 Pretorius Street, Pretoria, 0002, South Africa.
BACKGROUND: Diabetes is a serious and growing public health concern in South
Africa, but its prevalence and distribution in pregnant women is not well known.
Women diagnosed with diabetes during pregnancy have a substantially greater risk
of adverse health outcomes for both mother and child. This study aims to
determine the prevalence and social determinants of diabetes during pregnancy in
South Africa.
METHODS: Data used in this study were from the 2012 South African National
Nutrition and Health Examination Survey; a nationally representative
cross-sectional household survey. The analysis was restricted to girls and women
between the ages of 15 to 49 years who self-reported ever being pregnant
(n = 4261) Logistic regression models were constructed to analyse the
relationship between diabetes during pregnancy and several indicators including
race, family history of diabetes, household income, area of residence and
obesity.
RESULTS: The prevalence of diabetes during pregnancy in South Africa was 3% (144
women) of all women who reported ever being pregnant. The majority of the women
who had ever had diabetes were African (70%), 51% were unemployed and 76% lived
in rural areas. Factors strongly associated with diabetes during pregnancy were
age (1.04 [Odds Ratio], 0.01 [Standard Error]), family history of diabetes (3.04;
0.8) and race (1.91; 0.53).
CONCLUSION: The analysis will contribute to an understanding of the prevalence of
diabetes during pregnancy and its social determinants. This will help in the
development of effective interventions targeted at improving maternal and child
health for mothers at high risk.
DOI: 10.1186/s12884-016-1218-z
PMCID: PMC5223373
234. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018
Jun 15.
Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic
Analysis.
Carlsson Petri KC(1), Ingwersen SH(2), Flint A(2), Zacho J(2), Overgaard RV(2).
Author information:
(1)Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
KCC@NovoNordisk.com.
(2)Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
INTRODUCTION: Semaglutide, a new treatment option approved for the treatment of
patients with type 2 diabetes mellitus, is a glucagon-like peptide-1 receptor
agonist to be injected subcutaneously once weekly. This analysis used a
population pharmacokinetic model of semaglutide to identify clinically relevant
covariates for exposure.
METHODS: A total of 1612 patients with up to seven pharmacokinetic observations

each were included in the analysis. All subjects had type 2 diabetes mellitus and
were enrolled in one of five trials in the phase III development program for
subcutaneous semaglutide once weekly (the SUSTAIN program). The treatment
duration of the trials varied from 30 to 104 weeks.
RESULTS: No clinically relevant effects on the exposure were seen for sex, age,
race, ethnicity, renal function, or injection site used, and semaglutide exposure
was stable over time. Of the covariates chosen, only body weight had a relevant
effect on the exposure of semaglutide. Few subjects developed semaglutide
antibodies, and the antibodies had no effect on exposure. Dose proportionality
was shown for the 0.5 mg and 1.0 mg maintenance doses of semaglutide.
CONCLUSION: The population pharmacokinetic study showed that semaglutide exposure
is not affected by covariates other than body weight at either a maintenance dose
of 0.5 or 1.0 mg semaglutide. Therefore, we conclude that no semaglutide dose
adjustments are needed in different populations. This finding is to be further
explored in an exposure-response analysis.
TRIAL REGISTRATION: The trials were registered at ClinicalTrials.gov
(identifiers: NCT02054897, NCT01930188, NCT01885208, NCT01720446 and
NCT02207374).
FUNDING: Novo Nordisk A/S, Bagsværd, Denmark.
DOI: 10.1007/s13300-018-0458-5
PMCID: PMC6064581
PMID: 29907893
235. Korean J Fam Med. 2018 Sep;39(5):313-317. doi: 10.4082/kjfm.17.0122. Epub 2018
Jul 31.
Serum Branched Chain Amino Acids Are Associated with Type 2 Diabetes Mellitus in
Jordan.
Alfaqih MA(1), Abu-Khdair Z(1), Saadeh R(1), Saadeh N(1), Al-Dwairi A(1),
Al-Shboul O(1).
Author information:
(1)Faculty of Medicine, Jordan University of Science and Technology, Irbid,
Jordan.
BACKGROUND: Diabetes mellitus is a global public health problem that is caused by
the lack of insulin secretion (type 1) or resistance to its action (type 2). A
low insulin-to-glucagon ratio predicts an increase in the serum levels of
branched chain amino acids, a feature confirmed in several populations. This
relationship has not been assessed in Jordan. The objective of this study was to
investigate the association between serum branched chain amino acids and type 2
diabetes mellitus in patients in Jordan.
METHODS: Two hundred type 2 diabetes mellitus patients and an additional 200
non-diabetic controls were recruited. Age, body mass index, and waist
circumference of the subjects were recorded. Branched chain amino acid, total
cholesterol, and triglyceride levels were measured from the collected serum
samples.
RESULTS: Serum branched chain amino acid levels were significantly higher in type
2 diabetes mellitus patients than in non-diabetes individuals (P<0.0001). In
binomial regression analysis, serum branched chain amino acid levels remained
significantly associated with diabetes mellitus and increased its risk (odds
ratio, 1.004; 95% confidence interval, 1.001-1.006; P=0.003).
CONCLUSION: Type 2 diabetes mellitus is associated with higher branched chain
amino acid levels in Jordan independent of age, sex, body mass index, waist
circumference, and total serum cholesterol and serum triglyceride levels.
DOI: 10.4082/kjfm.17.0122
PMCID: PMC6166113
PMID: 30060645
236. Diabet Med. 2018 Jul;35(7):862-870. doi: 10.1111/dme.13613. Epub 2018 Mar 15.
Setting the top 10 research priorities to improve the health of people with Type
2 diabetes: a Diabetes UK-James Lind Alliance Priority Setting Partnership.
Finer S(1), Robb P(2), Cowan K(2), Daly A(3), Shah K(4), Farmer A(5).
Author information:
(1)Centre for Primary Care and Public Health, Blizard Institute, Barts and the
London School of Medicine and Dentistry, Queen Mary University of London, London.
(2)James Lind Alliance, University of Southampton, Southampton.
(3)Independent Information Specialist, Solihull, UK.
(4)Diabetes UK, London.
Oxford, UK.
AIMS: To describe processes and outcomes of a priority setting partnership to
identify the 'top 10 research priorities' in Type 2 diabetes, involving people
living with the condition, their carers, and healthcare professionals.
METHODS: We followed the four-step James Lind Alliance Priority Setting
Partnership process which involved: gathering uncertainties using a questionnaire
survey distributed to 70 000 people living with Type 2 diabetes and their carers,
and healthcare professionals; organizing the uncertainties; interim priority
setting by resampling of participants with a second survey; and final priority
setting in an independent group of participants, using the nominal group
technique. At each step the steering group closely monitored and guided the
process.
RESULTS: In the first survey, 8227 uncertainties were proposed by 2587
participants, of whom 18% were from black, Asian and minority ethnic groups.
Uncertainties were formatted and collated into 114 indicative questions. A total
of 1506 people contributed to a second survey, generating a shortlist of 24
questions equally weighted to the contributions of people living with diabetes
and their carers and those of healthcare professionals. In the final step the
'top 10 research priorities' were selected, including questions on cure and
reversal, risk identification and prevention, and self-management approaches in
Type 2 diabetes.
CONCLUSION: Systematic and transparent methodology was used to identify research
priorities in a large and genuine partnership of people with lived and
professional experience of Type 2 diabetes. The top 10 questions represent
consensus areas of research priority to guide future research, deliver responsive
and strategic allocation of research resources, and improve the future health and
well-being of people living with, and at risk of, Type 2 diabetes.
DOI: 10.1111/dme.13613
PMCID: PMC6032840
PMID: 29485717
237. Int J Endocrinol. 2017;2017:6039356. doi: 10.1155/2017/6039356. Epub 2017 Feb 20.
Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular
Diseases: Results from a Population-Based Study in Italy.
Ballotari P(1), Venturelli F(2), Greci M(3), Giorgi Rossi P(1), Manicardi V(4).
Author information:
(1)Interinstitutional Epidemiology Unit, Local Health Authority of Reggio Emilia,

Via Amendola 2, 42122 Reggio Emilia, Italy; Arcispedale Santa Maria Nuova-IRCCS,
Reggio Emilia, Viale Umberto I 50, 42123 Reggio Emilia, Italy.
(2)Department of Biomedical, Metabolic and Neural Sciences, University of Modena
and Reggio Emilia, Via Campi 287, 41126 Modena, Italy.
(3)Primary Care Department, Local Health Authority of Reggio Emilia, Via Amendola
2, 42122 Reggio Emilia, Italy.
(4)Internal Medicine Department, Montecchio Hospital, Local Health Authority of
Reggio Emilia, Via Barilla 16, 42027 Montecchio, Italy.
The aim of the study is to assess sex difference in association between type 2
diabetes and incidence of major cardiovascular events, that is, myocardial
infarction, stroke, and heart failure, using information retrieved by diabetes
register. The inhabitants of Reggio Emilia (Italy) aged 30-84 were followed
during 2012-2014. Incidence rate ratios and 95% confidence intervals were
calculated using multivariate Poisson model. The age- and sex-specific event
rates were graphed. Subjects with type 2 diabetes had an excess risk compared to
their counterparts without diabetes for all the three major cardiovascular
events. The excess risk is similar in women and men for stroke (1.8 times) and
heart failure (2.7 times), while for myocardial infarction, the excess risk in
women is greater than the one observed in men (IRR 2.58, 95% CI 2.22-3.00 and IRR
1.78, 95% CI 1.60-2.00, resp.; P of interaction < 0.0001). Women had always a
lesser risk than men, but in case of myocardial infarction, the women with type 2
diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95%
CI 0.53-0.72 and IRR 0.36, 95% CI 0.33-0.39, resp.). In women with type 2
diabetes, the risk of major cardiovascular events is anticipated by 20-30 years,
while in men it is by 15-20.
DOI: 10.1155/2017/6039356
PMCID: PMC5338069
PMID: 28316624
Conflict of interest statement: The authors declare that there is no conflict of
interests regarding the publication of this paper.
238. Lancet Diabetes Endocrinol. 2018 Jul;6(7):538-546. doi:
10.1016/S2213-8587(18)30079-2. Epub 2018 May 8.
Sex-specific relevance of diabetes to occlusive vascular and other mortality: a
collaborative meta-analysis of individual data from 980 793 adults from 68
prospective studies.
Prospective Studies Collaboration and Asia Pacific Cohort Studies Collaboration.
Collaborators: Gnatiuc L, Herrington WG, Halsey J, Tuomilehto J, Fang X, Kim HC,
De Bacquer D, Dobson AJ, Criqui MH, Jacobs DR Jr, Leon DA, Peters S, Ueshima H,
Sherliker P, Peto R, Collins R, Huxley RR, Emberson JR, Woodward M, Lewington S,
Aoki N, Arima H, Arnesen E, Aromaa A, Assmann G, Bachman DL, Baigent C,
Bartholomew H, Benetos A, Bengtsson C, Bennett D, Björkelund C, Blackburn H,
Bonaa K, Boyle E, Broadhurst R, Carstensen J, Chambless L, Chen Z, Chew SK,
Clarke R, Cox C, Curb JD, D'Agostino R, Date C, Davey Smith G, De Backer G,
Dhaliwal SS, Duan XF, Ducimetiere P, Duffy S, Eliassen H, Elwood P, Empana J,
Garcia-Palmieri MH, Gazes P, Giles GG, Gillis C, Goldbourt U, Gu DF, Guasch-Ferre
M, Guize L, Haheim L, Hart C, Hashimoto S, Hashimoto T, Heng D, Hjermann I, Ho
SC, Hobbs M, Hole D, Holme I, Horibe H, Hozawa A, Hu F, Hughes K, Iida M, Imai K,
Imai Y, Iso H, Jackson R, Jamrozik K, Jee SH, Jensen G, Jiang CQ, Johansen NB,
Jorgensen T, Jousilahti P, Kagaya M, Keil J, Keller J, Kim IS, Kita Y, Kitamura
A, Kiyohara Y, Knekt P, Knuiman M, Kornitzer M, Kromhout D, Kronmal R, Lam TH,
Law M, Lee J, Leren P, Levy D, Li YH, Lissner L, Luepker R, Luszcz M, MacMahon S,
Maegawa H, Marmot M, Matsutani Y, Meade T, Morris J, Morris R, Murayama T, Naito
Y, Nakachi K, Nakamura M, Nakayama T, Neaton J, Nietert PJ, Nishimoto Y, Norton
R, Nozaki A, Ohkubo T, Okayama A, Pan WH, Puska P, Qizilbash N, Reunanen A, Rimm

E, Rodgers A, Saitoh S, Sakata K, Sato S, Schnohr P, Schulte H, Selmer R, Sharp
D, Shifu X, Shimamoto K, Shipley M, Silbershatz H, Sorlie P, Sritara P, Suh I,
Sutherland SE, Sweetnam P, Tamakoshi A, Tanaka H, Thomsen T, Tominaga S, Tomita
M, Törnberg S, Tunstall-Pedoe H, Tverdal A, Ueshima H, Vartiainen E, Wald N,
Wannamethee SG, Welborn TA, Whincup P, Whitlock G, Willett W, Woo J, Wu ZL, Yao
SX, Yarnell J, Yokoyama T, Yoshiike N, Zhang XH.
BACKGROUND: Several studies have shown that diabetes confers a higher relative
risk of vascular mortality among women than among men, but whether this increased
relative risk in women exists across age groups and within defined levels of
other risk factors is uncertain. We aimed to determine whether differences in
established risk factors, such as blood pressure, BMI, smoking, and cholesterol,
explain the higher relative risks of vascular mortality among women than among
men.
METHODS: In our meta-analysis, we obtained individual participant-level data from
studies included in the Prospective Studies Collaboration and the Asia Pacific
Cohort Studies Collaboration that had obtained baseline information on age, sex,
diabetes, total cholesterol, blood pressure, tobacco use, height, and weight.
Data on causes of death were obtained from medical death certificates. We used
Cox regression models to assess the relevance of diabetes (any type) to occlusive
vascular mortality (ischaemic heart disease, ischaemic stroke, or other
atherosclerotic deaths) by age, sex, and other major vascular risk factors, and
to assess whether the associations of blood pressure, total cholesterol, and
body-mass index (BMI) to occlusive vascular mortality are modified by diabetes.
RESULTS: Individual participant-level data were analysed from 980 793 adults.
During 9·8 million person-years of follow-up, among participants aged between 35
and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive
vascular disease. After controlling for major vascular risk factors, diabetes
roughly doubled occlusive vascular mortality risk among men (death rate ratio
[RR] 2·10, 95% CI 1·97-2·24) and tripled risk among women (3·00, 2·71-3·33; χ2
test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular
death RRs were higher in younger individuals (aged 35-59 years: 2·60, 2·30-2·94)
than in older individuals (aged 70-89 years: 2·01, 1·85-2·19; p=0·0001 for trend
across age groups), and, across age groups, the death RRs were higher among women
than among men. Therefore, women aged 35-59 years had the highest death RR across
all age and sex groups (5·55, 4·15-7·44). However, since underlying
confounder-adjusted occlusive vascular mortality rates at any age were higher in
men than in women, the adjusted absolute excess occlusive vascular mortality
associated with diabetes was similar for men and women. At ages 35-59 years, the
excess absolute risk was 0·05% (95% CI 0·03-0·07) per year in women compared with
0·08% (0·05-0·10) per year in men; the corresponding excess at ages 70-89 years
was 1·08% (0·84-1·32) per year in women and 0·91% (0·77-1·05) per year in men.
Total cholesterol, blood pressure, and BMI each showed continuous log-linear
associations with occlusive vascular mortality that were similar among
individuals with and without diabetes across both sexes.
INTERPRETATION: Independent of other major vascular risk factors, diabetes
substantially increased vascular risk in both men and women. Lifestyle changes to
reduce smoking and obesity and use of cost-effective drugs that target major
vascular risks (eg, statins and antihypertensive drugs) are important in both men
and women with diabetes, but might not reduce the relative excess risk of
occlusive vascular disease in women with diabetes, which remains unexplained.
FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research
UK, European Union BIOMED programme, and National Institute on Aging (US National
Institutes of Health).
reserved.
DOI: 10.1016/S2213-8587(18)30079-2
PMCID: PMC6008496
PMID: 29752194
eCollection 2017.
Shared Medical Appointments May Be Effective for Improving Clinical and
Behavioral Outcomes in Type 2 Diabetes: A Narrative Review.
Menon K(1), Mousa A(1), de Courten MP(2), Soldatos G(1), Egger G(3), de Courten
B(1).
Author information:
(1)Monash Centre for Health Research and Implementation, School of Public Health
and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
(2)Centre for Chronic Disease, Victoria University, Australia, Melbourne, VIC,
Australia.
(3)Centre for Health Promotion and Research, Health and Human Sciences
Department, Southern Cross University, Lismore, NSW, Australia.
Type 2 diabetes mellitus (T2DM) is a complex chronic disease affecting over 400
million people worldwide. Managing T2DM and its associated complications in
individual patient consultations poses substantial challenges to physicians due
to limited time and resources and lack of access to multidisciplinary teams.
Shared medical appointments (SMAs) are consecutive medical consultations provided
by a physician in a group setting, where integrated medical care and patient
education are delivered in a single session. SMAs allow physicians to deliver the
same level of care to multiple patients at the same time, thereby maximizing
available resources. However, the effectiveness and practicality of SMAs in the
management of T2DM remains unknown. This narrative review summarizes current and
emerging evidence regarding the effectiveness of SMAs in improving clinical
outcomes in patients with T2DM, as well as whether SMAs are associated with
reduced costs and improved diabetes-related behavioral and lifestyle changes. An
extensive literature search was conducted on major electronic databases including
PubMed and Google Scholar using keywords, including SMAs, group visits, and T2DM
to identify all studies of SMAs in patients with T2DM. Studies in type 1 diabetes
or mixed or unspecified populations were excluded, as well as studies where SMAs
did not involve a physician since these do not meet the classical definition of a
SMA. Nineteen studies were identified and are included in this review. Overall,
current evidence suggests that SMAs delivered regularly over time may be
effective in improving glycemic outcomes, diabetes knowledge, and some
diabetes-related behaviors. However, the main limitation of existing studies was
the paucity of comparisons with standard care which limits the ability to draw
conclusions regarding whether SMAs are superior to standard care in T2DM
management. Moreover, the small number of studies and substantial heterogeneity
in study designs, populations, and interventions creates difficulties in
establishing the practicality and efficiency of SMAs in the clinical care
setting. We conclude that there remains a need for larger studies to identify
populations who may or may not benefit from the SMA model of care and to clarify
the potential benefits and barriers to implementing SMAs into routine diabetes
care.
DOI: 10.3389/fendo.2017.00263
PMCID: PMC5632846
PMID: 29046662
240. Perm J. 2018;22. doi: 10.7812/TPP/17-050.
A Simple Model for Predicting Two-Year Risk of Diabetes Development in
Individuals with Prediabetes.
Glauber H(1), Vollmer WM(2), Nichols GA(3).

Author information:
(1)Retired Endocrinologist, formerly at the Sunnyside Medical Center in
Clackamas, OR, and the Center for Health Research in Portland, OR, and former
Visiting Scientist at the Galil Center for Telemedicine, Medical Informatics and
Personalized Medicine at RB Rappaport Faculty of Medicine, Technion Israel
Institute of Technology in Haifa. harryg123123@gmail.com.
(2)Senior Investigator at the Center for Health Research in Portland, OR.
william.vollmer@kpchr.org.
(3)Senior Investigator at the Center for Health Research in Portland, OR.
greg.nichols@kpchr.org.
CONTEXT: Given the dramatic rise in the incidence of type 2 diabetes mellitus
(T2DM) in recent decades, identifying individuals at increased risk of T2DM and
validating methods to reduce their risk of disease progression is important. With
more than one-third of US adults having prediabetes, a more precise
stratification of absolute risk of T2DM incidence would help in prioritizing
prevention efforts.
OBJECTIVE: To develop a simple and clinically useful schema to stratify
short-term (2-year) absolute risk of T2DM.
DESIGN: Observational study of more than 77,000 adult members (age 18-75 years)
from 3 Regions of the Kaiser Foundation Health Plan with prediabetes (hemoglobin
A1C [HbA1C] = 5.7%-6.4%).
MAIN OUTCOME MEASURES: The 2-year probability for development of diabetes as a
function of baseline HbA1C and body mass index (BMI).
RESULTS: The 2-year risk of diabetes diagnosis varied widely by HbA1C and BMI. A
small subset (5.2%) had a very high risk of T2DM developing within 2 years.
Another 13.3% had a moderate 2-year risk of T2DM, whereas most (81.5%) of the
population was at much lower risk. Thus, most Kaiser Foundation Health Plan
members with prediabetes have only modest risk of progression to T2DM within 2
years.
CONCLUSION: Using HbA1C and BMI, we created a simple stratification scheme to
more precisely estimate risk of T2DM incidence. This will enable more efficient
assignment of prevention interventions and clinical and laboratory follow-up to
the small subset at highest risk, while minimizing the potentially negative
effects of overdiagnosis among the majority with prediabetes who are not at high
short-term risk of T2DM.
DOI: 10.7812/TPP/17-050
PMCID: PMC5760055
PMID: 29309270
241. Front Pharmacol. 2018 Jun 22;9:677. doi: 10.3389/fphar.2018.00677. eCollection
2018.
Sitagliptin and Fractures in Type 2 Diabetes: A Nationwide Population-Based
Propensity-Matching Study.
Lin SY(1)(2), Hsu WH(1)(3), Lin CC(1)(4), Lin CL(5)(6), Tsai CH(1)(7), Yeh HC(1),
Hsu CY(8), Kao CH(1)(9)(10).
Author information:
(1)Graduate Institute of Clinical Medical Science, College of Medicine, China
Medical University, Taichung, Taiwan.
(2)Division of Nephrology and Kidney Institute, China Medical University
Hospital, Taichung, Taiwan.
(3)Division of Pulmonary and Critical Care Medicine, China Medical University
Hospital and China Medical University, Taichung, Taiwan.
(4)Department of Family Medicine, China Medical University Hospital, Taichung,
Taiwan.
(5)Management Office for Health Data, China Medical University Hospital,

Taichung, Taiwan.
(6)College of Medicine, China Medical University, Taichung, Taiwan.
(7)Department of Orthopedics, China Medical University Hospital, Taichung,
Taiwan.
(8)Graduate Institute of Clinical Medical Science, China Medical University,
Taichung, Taiwan.
(9)Department of Nuclear Medicine, China Medical University Hospital, Taichung,
Taiwan.
(10)Department of Bioinformatics and Medical Engineering, Asia University,
Taichung, Taiwan.
Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor possibly affects bone
turnover. We conducted this cohort study to determine whether sitagliptin is
associated with an increased risk of fracture. Methods: The sitagliptin cohort
included 1,578 patients aged 20 years and above. The nonsitagliptin cohort
comprised propensity-score matched patients at a ratio of 1:1. The primary
outcome was the incidence of fractures, which was evaluated using Kaplan-Meier
survival analysis and proportional hazards modeling. Results: The mean age of
patients in the sitagliptin and nonsitagliptin cohorts was 63.1 and 63.3 years,
respectively. The incidence of fractures in the sitagliptin cohort was 46 per
1,000 person-years and that in the nonsitagliptin cohort was 40.8 per 1,000
person-years. Compared with patients in the nonsitagliptin cohort, those in the
sitagliptin cohort who received sitagliptin for ≥250 days had a higher risk of
fracture (aHR = 1.32, 95% CI = 1.06-1.64). Conclusion: Using sitaglipin ≥250 days
was associated with an increased risk of fracture.
DOI: 10.3389/fphar.2018.00677
PMCID: PMC6025224
PMID: 29988467
242. Sci Rep. 2017 Jan 27;7:41518. doi: 10.1038/srep41518.
Six-year changes in the prevalence of obesity and obesity-related diseases in
Northeastern China from 2007 to 2013.
Wu J(1), Xu H(2), He X(1), Yuan Y(3), Wang C(1), Sun J(1), He S(1), Niu J(2).
Author information:
(1)Department of Gerontology, the First Hospital attached to Jilin University,
Xinmin Street, Changchun 130021, China.
(2)Department of Hepatology, the First Hospital attached to Jilin University,
Xinmin Street, Changchun 130021, China.
(3)Department of Rheumatology and Immunology, the First Hospital attached to
Jilin University, Xinmin Street, Changchun 130021, China.
Obesity and obesity-related diseases are important public health challenges. In
this study, we aimed to provide updated trends in the prevalence of these
conditions. We conducted two independent cross-sectional surveys of the general
population aged 20-75 years in 2007 and 2013 in Jilin, China. A total of 3636
(1719 males) and 1359 (602 males) participants were enrolled in the 2007 and 2013
surveys, respectively. Obesity-related diseases were defined as type 2 diabetes,
hypertension, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). The
age-standardized prevalence of obesity, overweight, diabetes, pre-diabetes,
dyslipidemia and NAFLD increased from 2007 to 2013 from 15.82% to 19.41%, 35.85%
to 41.80%, 6.37% to 9.23%, 16.77% to 23.49%., 53.46% to 65.50%, and 23.48% to
44.31% in males, respectively, and from 13.18% to 18.77%, 31.11% to 37.54%, 4.41%
to 8.48%, 8.10% to 16.49%, 41.96% to 54.70%, and 17.56% to 43.06% in females,
respectively. However, the prevalence of hypertension remained stable (males:
38.10% vs. 38.63% and females: 33.04% vs. 33.01% in 2007 and 2013, respectively).
The prevalence of obesity and obesity-related diseases, except for hypertension,
increased significantly in the general population in Northeastern China. More

targeted measures should be implemented to address the serious challenges
presented by these diseases.
DOI: 10.1038/srep41518
PMCID: PMC5269745
Conflict of interest statement: The authors declare no competing financial
interests.
243. SSM Popul Health. 2016 Dec 28;3:172-178. doi: 10.1016/j.ssmph.2016.12.012.
eCollection 2017 Dec.
Socioeconomic inequality in morbid obesity with body mass index more than
40 kg/m2 in the United States and England.
Booth HP(1), Charlton J(1), Gulliford MC(1).
Author information:
UK.
Introduction: This study evaluated socioeconomic inequality in morbid obesity
(body mass index, BMI ≥40 kg/m2) through an analysis of population health survey
data in the United States (US) and England (UK).
Methods: We analysed data for the National Health and Nutrition Examination
Survey and the Health Survey for England for 2011 to 2014. Age-adjusted odds
ratios (AOR) were used to evaluate income- and education-inequality.
Results: There were 26,898 eligible UK and 10,628 US participants. Morbid obesity
was more frequent in women than men, and higher in the US than the UK (men: US,
4.8%; UK, 1.7%; women US, 9.6%; UK, 3.7%). In the UK, morbid obesity showed
graded income-inequality in both genders (AOR, for lowest income quintile: men,
1.83, 95% confidence interval 1.16 to 2.88; women, 2.18, 1.55 to 3.07), as well
as education-inequality (AOR for no school qualifications, men 2.57, 1.64 to
4.02; women, 2.18, 1.55 to 3.07). In the US, morbid obesity showed a consistent
gradient only for income in women (AOR for lowest income quintile 1.97, 1.19 to
3.25). When compared with all other US groups, having college education (AOR,
men, 0.56, 0.29 to 1.08; women, 0.36, 0.22 to 0.60) or household income ≥$75 000
(AOR, men 0.52, 0.27 to 0.98; women, 0.51, 0.33 to 0.80) appeared to protect
against morbid obesity.
Conclusions: Morbid obesity is associated with lower socioeconomic status in men
and women in the UK. In the US, morbid obesity was twice as prevalent, but less
strongly associated with socioeconomic status, suggesting that morbid obesity may
now have spread to all but the highest socioeconomic groups.
DOI: 10.1016/j.ssmph.2016.12.012
PMCID: PMC5769007
PMID: 29349213
244. J Glob Health. 2017 Jun;7(1):011103. doi: 10.7189/jogh.07.011103.
Socioeconomic status and prevalence of type 2 diabetes in mainland China, Hong
Kong and Taiwan: a systematic review.
Wu H(1), Meng X(1), Wild SH(1), Gasevic D(1), Jackson CA(1).
Author information:
(1)Usher Institute of Population Health Sciences and Informatics, University of
Edinburgh, Edinburgh, Scotland, UK.

BACKGROUND: China is estimated to have had the largest number of people with
diabetes in the world in 2015, with extrapolation of existing data suggesting
that this situation will continue until at least 2030. Type 2 diabetes has been
reported to be more prevalent among people with low socioeconomic status (SES) in
high-income countries, whereas the opposite pattern has been found in studies
from low- and middle-income countries. We conducted a systematic review to
describe the cross-sectional association between SES and prevalence of type 2
diabetes in Chinese in mainland China, Hong Kong and Taiwan.
METHODS: We conducted a systematic literature search in Medline, Embase and
Global Health electronic databases for English language studies reporting
prevalence or odds ratio for type 2 diabetes in a Chinese population for
different SES groups measured by education, income and occupation. We appraised
the quality of included studies using a modified Newcastle-Ottawa Scale.
Heterogeneity of studies precluded meta-analyses, therefore we summarized study
results using a narrative synthesis.
RESULTS: Thirty-three studies met the inclusion criteria and were included in the
systematic review. The association between education, income and occupation and
type 2 diabetes was reported by 27, 19 and 12 studies, respectively. Most, but
not all, studies reported an inverse association between education and type 2
diabetes, with odds ratios (OR) and 95% confidence interval (CI) ranging from
0.39 (CI not reported) to 1.52 (95% CI 0.91 - 2.54) for the highest compared to
the lowest education level. The association between income and type 2 diabetes
was inconsistent between studies. Only a small number of studies identified a
significant association between occupation and type 2 diabetes. Retired people
and people working in white collar jobs were reported to have a higher risk of
type 2 diabetes than other occupational groups even after adjusting for age.
CONCLUSIONS: This first systematic review of the association between individual
SES and prevalence of type 2 diabetes in China found that low education is
probably associated with an increased prevalence of type 2 diabetes, while the
association between income and occupation and type 2 diabetes is unclear.

DOI: 10.7189/jogh.07.011103
PMCID: PMC5481892
Conflict of interest statement: Competing interests: Sarah H Wild reports
honoraria for lectures on epidemiology of diabetes from Global MedEd/Astra Zeneca
and on the Scottish Diabetes Register from Novo Nordisk. All authors have
completed the ICMJE uniform disclosure form at
http://www.icmje.org/coi_disclosure.pdf (available upon request from the
corresponding author) and declare no other conflicts of interest.
245. Indian J Endocrinol Metab. 2017 Nov-Dec;21(6):909-918. doi:
10.4103/ijem.IJEM_85_17.
Sodium-glucose Cotransporter-2 Inhibitors: Moving Beyond the Glycemic Treatment
Goal.
Gupta V(1), Canovatchel W(2), Lokesh BN(3), Santani R(3), Garodia N(3).
Author information:
(1)VG-Advantage Diabetes, Thyroid and Endocrine Center, Mumbai, Maharashtra,
India.
(2)Janssen Research and Development, LLC, Raritan, NJ, USA.
(3)Janssen Medical Affairs, Mumbai, Maharashtra, India.
Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM)
that extend beyond the role of insulin and glucose utilization have been crucial
in redefining the treatment paradigm. The focus of treatment is currently
directed towards achieving wide-ranging targets encompassing the management of
cardiovascular comorbidities that have been evidenced as indispensable aspects of

T2DM. While most currently prescribed antihyperglycemic agents have little or no
effect on reducing cardiovascular risks, some have been associated with
undesirable effects on common risk factors such as weight gain and cardiovascular
sequelae. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are newer additions
to the array of therapeutic agents for T2DM that have demonstrated robust
glycemic control as mono and add-on therapies. Their unique renal mode of action,
independent of insulin modulation, confers complementary metabolic benefits. By
virtue of these effects, SGLT2i may have a distinct role in the revised treatment
recommendations by established working groups such as the American Diabetes
Association and the American Association of Clinical Endocrinologists that
advocate a more comprehensive management of T2DM, not restricting to glycemic
targets. The current review gives an overview of the changing treatment needs for
T2DM and discusses the nonglycemic effects of SGLT2i. It provides an updated
summary on the efficacy of canagliflozin, dapagliflozin, and empagliflozin in
promoting weight loss, stabilizing blood pressure, and other favorable metabolic
effects.
DOI: 10.4103/ijem.IJEM_85_17
PMCID: PMC5729683
PMID: 29285458
Conflict of interest statement: Dr. Nishant Garodia is an employee of Janssen
India. Dr. William Canovatchel is an employee of Janssen Research & Development,
LLC, USA, and holds company stocks. Dr. Vishal Gupta has received honoraria as a
consultant from Janssen India. Dr. B. N. Lokesh was an employee of Janssen India
at the time of conception of this review article. Dr. Ravi Santani was an
employee of Janssen India until manuscript submission.
246. BMC Public Health. 2017 Jan 6;17(1):31. doi: 10.1186/s12889-016-3929-5.

Study Protocol: The Norfolk Diabetes Prevention Study [NDPS]: a 46 month multi -
centre, randomised, controlled parallel group trial of a lifestyle intervention
[with or without additional support from lay lifestyle mentors with Type 2
diabetes] to prevent transition to Type 2 diabetes in high risk groups with non -
diabetic hyperglycaemia, or impaired fasting glucose.
Pascale M(1)(2), Murray N(1)(2), Bachmann M(3), Barton G(4)(5), Clark A(5)(6),
Howe A(3), Greaves C(7), Sampson M(8)(9).
Author information:
(1)Norfolk Diabetes Prevention Study, Norfolk and Norwich University Hospital NHS
Trust, Norwich, UK.
(2)Directorate of Diabetes and Endocrinology, Elsie Bertram Diabetes Centre,
Norfolk and Norwich University Hospital NHS Trust, Norwich, NR4 7UY, UK.
(3)Department of Population Health and Primary Care, Norwich Medical School,
University of East Anglia, Norwich, UK.
(4)Health Economics Group, Norwich Medical School, University Of East Anglia,
Norwich, UK.
(5)Norwich Clinical Trials Unit, Faculty of Medicine and Health Sciences,
University of East Anglia, Norwich, UK.
(6)Norwich Medical School, University of East Anglia, Norwich, UK.
(7)University of Exeter Collaboration for Academic Primary Care (APEx),
University of Exeter Medical School, Exeter, UK.
(8)Norfolk Diabetes Prevention Study, Norfolk and Norwich University Hospital NHS
Trust, Norwich, UK. mike.sampson@nnuh.nhs.uk.
(9)Directorate of Diabetes and Endocrinology, Elsie Bertram Diabetes Centre,
Norfolk and Norwich University Hospital NHS Trust, Norwich, NR4 7UY, UK.
mike.sampson@nnuh.nhs.uk.
BACKGROUND: This 7 year NIHR programme [2011-2018] tests the primary hypothesis
that the NDPS diet and physical activity intervention will reduce the risk of
transition to type 2 diabetes (T2DM) in groups at high risk of Type 2 diabetes.
The NDPS programme recognizes the need to reduce intervention costs through group
delivery and the use of lay mentors with T2DM, the realities of normal primary
care, and the complexity of the current glycaemic categorisation of T2DM risk.
METHODS: NDPS identifies people at highest risk of T2DM on the databases of 135
general practices in the East of England for further screening with ab fasting
plasma glucose and glycosylated haemoglobin [HbA1c]. Those with an elevated
fasting plasma glucose [impaired fasting glucose or IFG] with or without an
elevated HbA1c [non -diabetic hyperglycaemia; NDH] are randomised into three
treatment arms: a control arm receiving no trial intervention, an arm receiving
an intensive bespoke group-based diet and physical activity intervention, and an
arm receiving the same intervention with enhanced support from people with T2DM
trained as diabetes prevention mentors [DPM]. The primary end point is cumulative
transition rates to T2DM between the two intervention groups, and between each
intervention group and the control group at 46 months. Participants with screen
detected T2DM are randomized into an equivalent prospective controlled trial with
the same intervention and control arms with glycaemic control [HbA1c] at
46 months as the primary end point. Participants with NDH and a normal fasting
plasma glucose are randomised into an equivalent prospective controlled
intervention trial with follow up for 40 months. The intervention comprises six
education sessions for the first 12 weeks and then up to 15 maintenance sessions
until intervention end, all delivered in groups, with additional support from a
DPM in one treatment arm.
DISCUSSION: The NDPS programme reports in 2018 and will provide trial outcome
data for a group delivered diabetes prevention intervention, supported by lay
mentors with T2DM, with intervention in multiple at risk glycaemic categories,
and that takes into account the realities of normal clinical practice.
TRIAL REGISTRATION: ISRCTN34805606 (Retrospectively registered 16.3.16).
DOI: 10.1186/s12889-016-3929-5
PMCID: PMC5217324
247. BMC Endocr Disord. 2018 Oct 1;18(1):69. doi: 10.1186/s12902-018-0297-4.
Switching from glargine+insulin aspart to glargine+insulin aspart 30 before
breakfast combined with exercise after dinner and dividing meals for the
treatment of type 2 diabetes patients with poor glucose control - a prospective
cohort study.
Li J(1), Wang L(2), Chen F(2), Xia D(2), Miao L(2).
Author information:
(1)Department of Endocrinology, The Affiliated Hospital of Medical School of
Ningbo University, Zhejiang, China. 627168316@qq.com.
(2)Department of Endocrinology, The Affiliated Hospital of Medical School of
Ningbo University, Zhejiang, China.
BACKGROUND: This study aimed to examine the switch from glargine+once daily
insulin aspart (1 + 1 regimen) to glargine+insulin aspart 30 before breakfast
combined with exercise and in patients with type 2 diabetes mellitus (T2DM) with
poorly controlled blood glucose levels.
METHODS: Consecutive patients with poorly controlled T2DM (n = 182) were switched
from the 1 + 1 regimen to glargine+insulin aspart 30 before breakfast in
combination with exercise after dinner and dividing meals in two (same final
calories intake). The insulin doses were adjusted according to blood glucose
levels within 4 weeks after the switch and maintained for 12 weeks. Fasting blood
glucose (FBG), 2-hpostprandial glucose (2hPG), glycosylated hemoglobin (HbA1c),
body mass index (BMI), daily insulin dose, and hypoglycemia events were assessed.
RESULTS: Sixteen weeks after the switch, 2 h PG levels and HbA1c levels (from 8.5
to 7.4%, P = 0.001) were improved. The proportions of patients reaching the HbA1c
targets of 7.5% were improved (from 22.5 to 58.7%, P = 0.001). Among the 182
patients, 24 (13.2%) divided one meal into two meals, and 23 (12.6%) divided two
meals into four meals. Among all patients, 8.5% had to reuse insulin aspart
before dinner after the study. One patient with diarrhea and poor appetite
experienced severe hypoglycemia. The rate of hypoglycemia was 3.76
events/patient-year. The daily insulin Aspart 30 dose was higher than the
original insulin aspart dose (P = 0.001).
CONCLUSIONS: For patients with poorly controlled T2DM under the 1 + 1 regimen,
switching to glargine+insulin aspart 30 before breakfast combined with exercise
after dinner and dividing meals showed promising benefits.
DOI: 10.1186/s12902-018-0297-4
PMCID: PMC6167858
PMID: 30285711
248. Nutrients. 2018 Apr 18;10(4). pii: E503. doi: 10.3390/nu10040503.
Taiwanese Green Propolis Ethanol Extract Delays the Progression of Type 2
Diabetes Mellitus in Rats Treated with Streptozotocin/High-Fat Diet.
Chen LH(1), Chien YW(2)(3)(4), Chang ML(5), Hou CC(6), Chan CH(7), Tang HW(8),
Huang HY(9)(10).
Author information:
(1)Graduate Institute of Biomedical Electronics and Bioinformatics, National
Taiwan University, Taipei City 10617, Taiwan. lihan.h.chen@gmail.com.
(2)School of Nutrition and Health Sciences, Taipei Medical University, Taipei
City 11031, Taiwan. ychien@tmu.edu.tw.
(3)Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical
University, Taipei City 11031, Taiwan. ychien@tmu.edu.tw.

(4)Graduate Institute of Metabolism and Obesity Science, Taipei Medical
University, Taipei City 11031, Taiwan. ychien@tmu.edu.tw.
(5)Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih
Chien University, Taipei City 10462, Taiwan. mlchang@g2.usc.edu.tw.
(6)Department of Research & Development, NatureWise Biotech & Medicals
Corporation, Taipei City 10559, Taiwan. alison.hou@naturewise.com.tw.
Corporation, Taipei City 10559, Taiwan. llfonly_520@hotmail.com.
Corporation, Taipei City 10559, Taiwan. 9808408@gmail.com.
(9)Graduate Institute of Metabolism and Obesity Science, Taipei Medical
University, Taipei City 11031, Taiwan. maggieh323@hotmail.com.
Corporation, Taipei City 10559, Taiwan. maggieh323@hotmail.com.
Taiwanese green propolis ethanol extract (TGPE) is produced only in Taiwan and
has a different composition from other types of propolis. TGPE is known for its
anti-inflammation, anti-oxidation, and anti-microbial properties, but the effects
and mechanisms of TGPE in the modulation of diabetes are unclear. In this study,
we investigated the effects of TGPE on type 2 diabetes mellitus (T2DM) in a
streptozotocin/high-fat-diet (STZ/HFD)-induced T2DM rat model. The results
revealed that TGPE delayed the development and progression of T2DM and reduced
the severity of β-cell failure. TGPE also attenuated inflammation and
reactive oxygen species ROS in the rats. Moreover, there were higher levels of
oxidant cytokines, leptin, and adiponectin in the serum of the TGPE-treated
group. Unlike Brazilian propolis, TGPE promoted hepatic genes PPAR-α and
CYP7A1, which were related to lipid catabolism and removal. TGPE may thus delay
the progression of T2DM through anti-inflammation effects, anti-oxidation
effects, and balancing lipid metabolism. It is suggested that TGPE can be a
potential alternative medicine for T2DM.

DOI: 10.3390/nu10040503
PMCID: PMC5946288
249. Nutrients. 2017 Jun 13;9(6). pii: E600. doi: 10.3390/nu9060600.
Targeting Overconsumption of Sugar-Sweetened Beverages vs. Overall Poor Diet
Quality for Cardiometabolic Diseases Risk Prevention: Place Your Bets!
Arsenault BJ(1)(2), Lamarche B(3), Després JP(4)(5).
Author information:
(1)Centre de recherche de l'Institut universitaire de cardiologie et de
pneumologie de Québec, Y-2110, Pavillon Marguerite D'Youville, 2725 chemin
Ste-Foy, Québec City, QC G1V 4G5, Canada. benoit.arsenault@criucpq.ulaval.ca.
(2)Department of Medicine, Faculty of Medicine, Université Laval, Québec City, QC
G1V 0A6, Canada. benoit.arsenault@criucpq.ulaval.ca.
(3)School of Nutrition, Université Laval, Québec City, QC G1V 0A6, Canada.
Benoit.Lamarche@fsaa.ulaval.ca.
(4)Centre de recherche de l'Institut universitaire de cardiologie et de
pneumologie de Québec, Y-2110, Pavillon Marguerite D'Youville, 2725 chemin
Ste-Foy, Québec City, QC G1V 4G5, Canada. jean-pierre.despres@criucpq.ulaval.ca.
(5)Department of Kinesiology, Faculty of Medicine, Université Laval, Québec City,
QC G1V 0A6, Canada. jean-pierre.despres@criucpq.ulaval.ca.
Chronic overconsumption of sugar-sweetened beverages (SSBs) is amongst the
dietary factors most consistently found to be associated with obesity, type 2
diabetes (T2D) and cardiovascular disease (CVD) risk in large epidemiological
studies. Intervention studies have shown that SSB overconsumption increases
intra-abdominal obesity and ectopic lipid deposition in the liver, and also
exacerbates cardiometabolic risk. Similar to the prevalence of obesity and T2D,
national surveys of food consumption have shown that chronic overconsumption of
SSBs is skyrocketing in many parts of the world, yet with marked heterogeneity
across countries. SSB overconsumption is also particularly worrisome among
children and adolescents. Although the relationships between SSB overconsumption
and obesity, T2D, and CVD are rather consistent in epidemiological studies, it
has also been shown that SSB overconsumption is part of an overall poor dietary
pattern and is particularly prevalent among subgroups of the population with low
socioeconomic status, thereby questioning the major focus on SSBs to
target/prevent cardiometabolic diseases. Public health initiatives aimed
specifically at decreasing SSB overconsumption will most likely be successful in
influencing SSB consumption per se. However, comprehensive strategies targeting
poor dietary patterns and aiming at improving global dietary quality are likely
to have much more impact in addressing the unprecedented public health challenges
that we are currently facing.
DOI: 10.3390/nu9060600
PMCID: PMC5490579
250. J Diabetes Metab Disord. 2017 Aug 14;16:33. doi: 10.1186/s40200-017-0312-8.
eCollection 2017.
Technical efficiency of rural primary health care system for diabetes treatment
in Iran: a stochastic frontier analysis.
Qorbani M(1)(2)(3), Farzadfar F(3), Majdzadeh R(4), Mohammad K(4), Motevalian
A(1).
Author information:
(1)Department of Epidemiology, School of Public Health, Iran University of
(2)Non-communicable Diseases Research Center, Alborz University of Medical
Sciences, Karaj, Iran.
(3)Non-communicable Diseases Research Center, Endocrinology and Metabolism
Population Sciences Institute, Tehran University of Medical Sciences, Tehran,
Iran.
BACKGROUND: Our aim was to explore the technical efficiency (TE) of the Iranian
rural primary healthcare (PHC) system for diabetes treatment coverage rate using
the stochastic frontier analysis (SFA) as well as to examine the strength and
significance of the effect of human resources density on diabetes treatment.
METHODS: In the SFA model diabetes treatment coverage rate, as a output, is a
function of health system inputs (Behvarz worker density, physician density, and
rural health center density) and non-health system inputs (urbanization rate,
median age of population, and wealth index) as a set of covariates. Data about
the rate of self-reported diabetes treatment coverage was obtained from the
Non-Communicable Disease Surveillance Survey, data about health system inputs
were collected from the health census database and data about non-health system
inputs were collected from the census data and household survey.
RESULTS: In 2008, rate of diabetes treatment coverage was 67% (95% CI: 63%-71%)
nationally, and at the provincial level it varied from 44% to 81%. The TE score
at the national level was 87.84%, with considerable variation across provinces
(from 59.65% to 98.28%).Among health system and non-health system inputs, only
the Behvarz density (per 1000 population)was significantly associated with
diabetes treatment coverage (β (95%CI): 0.50 (0.29-0.70),p < 0.001).
CONCLUSION: Our findings show that although the rural PHC system can considered
efficient in diabetes treatment at the national level, a wide variation exists in
TE at the provincial level. Because the only variable that is predictor of TE is

the Behvarz density, the PHC system may extend the diabetes treatment coverage by
using this group of health care workers.
DOI: 10.1186/s40200-017-0312-8
PMCID: PMC5556340
PMID: 28815169
eCollection 2017.
Testosterone is protective against impaired glucose metabolism in male
intrauterine growth-restricted offspring.
Intapad S(1)(2), Dasinger JH(2), Fahling JM(2), Backstrom MA(2), Alexander BT(2).
Author information:
(1)Department of Pharmacology, Tulane University School of Medicine, New Orleans,
LA, United States of America.
(2)Department of Physiology and Biophysics, University of Mississippi Medical
Center, Jackson, MS, United States of America.
Placental insufficiency alters the intrauterine environment leading to increased
risk for chronic disease including impaired glucose metabolism in low birth
weight infants. Using a rat model of low birth weight, we previously reported
that placental insufficiency induces a significant increase in circulating
testosterone in male intrauterine growth-restricted offspring (mIUGR) in early
adulthood that is lost by 12 months of age. Numerous studies indicate
testosterone has a positive effect on glucose metabolism in men. Female
growth-restricted littermates exhibit glucose intolerance at 6 months of age.
Thus, the aim of this paper was to determine whether mIUGR develop impaired
glucose metabolism, and whether a decrease in elevated testosterone levels plays
a role in its onset. Male growth-restricted offspring were studied at 6 and 12
months of age. No impairment in glucose tolerance was observed at 6 months of age
when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched
control. Fasting blood glucose was significantly higher and glucose tolerance was
impaired with a significant decrease in circulating testosterone in mIUGR at 12
compared with 6 months of age. Castration did not additionally impair fasting
blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting
blood glucose was significantly elevated in castrated controls. Restoration of
elevated testosterone levels significantly reduced fasting blood glucose and
improved glucose tolerance in mIUGR. Thus, our findings suggest that the
endogenous increase in circulating testosterone in mIUGR is protective against
impaired glucose homeostasis.
PMCID: PMC5690651
252. Endocr Connect. 2018 Jan;7(1):220-231. doi: 10.1530/EC-17-0253. Epub 2017 Dec 12.
Testosterone level and risk of type 2 diabetes in men: a systematic review and
meta-analysis.
Yao QM(1), Wang B(1), An XF(1), Zhang JA(2), Ding L(3).
Author information:
(1)Department of EndocrinologyJinshan Hospital of Fudan University, Shanghai,
China.
(2)Department of EndocrinologyShanghai University of Medicine & Health Sciences
Affiliated Zhoupu Hospital, Shanghai, China zhangjinan@hotmail.com

dlm196969@163.com.
(3)Department of Clinical LaboratoryJinshan Hospital of Fudan University,
Shanghai, China zhangjinan@hotmail.com dlm196969@163.com.
BACKGROUND: Type 2 diabetes is a risk factor for testosterone deficiency and
impaired sex steroid status. Some studies also investigated the association of
testosterone level with diabetes risk in men, but reported controversial
findings. To clarify this issue, we conducted a systematic review and
meta-analysis.
METHODS: PubMed, EMBASE and Web of Science were searched for eligible cohort or
nested case-control studies published up to August 15, 2017. Meta-analysis was
used to calculate the pooled relative risk (RR) of type 2 diabetes associated
with higher testosterone level.
RESULTS: Thirteen cohort or nested case-control studies with 16,709 participants
were included. Meta-analysis showed that higher total testosterone level could
significantly decrease the risk of type 2 diabetes in men (RR = 0.65; 95% CI
0.50-0.84; P = 0.001), and higher free testosterone level could also decrease the
risk of type 2 diabetes in men (RR = 0.94; 95% CI 0.90-0.99; P = 0.014). After
excluding two studies that did not calculate RRs by quartiles of testosterone
levels, both higher total testosterone and free testosterone levels could
decrease the risk of type 2 diabetes in men, and the pooled RRs were 0.62 (95% CI
0.51-0.76; P < 0.001) and 0.77 (95% CI 0.61-0.98; P = 0.03), respectively.
CONCLUSION: This meta-analysis suggests that higher testosterone level can
significantly decrease the risk of type 2 diabetes in men. Therefore, combined
with previous researches, the findings above suggest a reverse-causality scenario
in the relation between testosterone deficiency and risk of type 2 diabetes in
men.
© 2018 The authors.
DOI: 10.1530/EC-17-0253
PMCID: PMC5793809
PMID: 29233816
253. BMC Cardiovasc Disord. 2017 May 2;17(1):106. doi: 10.1186/s12872-017-0537-y.
Time-cumulated blood pressure exposure and incident impairment of glucose
tolerance and diabetes mellitus.
Wu YT(1)(2), Song L(2)(3), Liu XX(4), Gao JS(2), Zheng XM(2), Ruan CY(2), Zhao
HY(2), Chen SH(5), Gao WY(6), Jonas JB(7), Wu SL(8).
Author information:
(1)School of Pharmaceutical Science and Technology, Tianjin University, Tianjin,
China.
(2)Department of Cardiology, Kailuan Hospital, North China University of Science
and Technology, Tangshan, 063000, China.
(3)Graduate school, North China University of Science and Technology, Tangshan,
China.
(4)Department of Cardiology, Tangshan People's Hospital, North China University
of Science and Technology, Tangshan, China.
(5)Department of Health Care Center, Kailuan Hospital, North China University of
Science and Technology, Tangshan, China.
(6)School of Pharmaceutical Science and Technology, Tianjin University, Tianjin,
China. biochemgao@163.com.
(7)Department of Ophthalmology, Medical Faculty Mannheim of the
Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
(8)Department of Cardiology, Kailuan Hospital, North China University of Science
and Technology, Tangshan, 063000, China. drwusl@163.com.
BACKGROUND: With the marked increase in the prevalence of diabetes mellitus, it

was the purpose of our study to assess a potential association of time-cumulated
exposure to systolic (CumSBP) and of diastolic blood pressure (CumDBP) with onset
of impaired glucose tolerance and diabetes mellitus.
METHODS: The prospective investigation included participants of the longitudinal
Kailuan Study with three baseline examinations in 2006-2007, 2008-2009 and
2010-2011, re-examination in 2012-2013, and no diabetes mellitus at baseline.
Cumulative blood pressure (BP) was calculated as
cumBP = [(BP1 + BP2)/2 × time1-2] + [(BP2 + BP3)/2 × time2-3]. Based on cumSBP,
the study population was stratified into four groups
(cumSBP < 480mmHgxyear;n = 15,339; 480mmHgxyear ≤ cumSBP < 520mmHgxyear;n = 7214;
520mmHgxyears ≤ cumSBP < 560mmHgxyears;n = 5675; and
cumSBP ≥ 560mmHgxyears;n = 10,576).
RESULTS: After adjusting for demographic, anthropomorphic, biochemical,
socioeconomic and lifestyle parameters and as compared with the first group, the
second, third and fourth group showed a significantly higher incidence of
diabetes (P-trend < 0.001;hazard ratio (HR);95% confidence interval
(CI):1.28(1.08,1.51),1.54(1.29,1.84), and 2.33(1.98,2.73), respectively), higher
incidence of impairment of glucose tolerance (P-trend < 0.001;HR;95%
CI1.17(1.02,1.33), 1.43(1.25,1.64), and 2.09(1.85,2.37), respectively), and
higher incidence of diabetes developing out of an impairment of glucose tolerance
(P-trend < 0.001;HR;95% CI:1.22(0.97,1.54),1.47(1.16,1.86), and 2.01(1.62,2.50),
respectively). An increase in cumSBP by 10 mmHg/year or an increase in cumDBP by
5 mmHg/year was associated with a hazard ratio of incident diabetes of 1.04 (95%
CI:1.03,1.04) and 1.02(1.02,1.03), respectively, with a hazard ratio of incident
impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and 1.03(95%
CI:1.02,1.03), respectively, and with a hazard ratio of incident diabetes
developing from impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and
1.03(95% CI:1.02,1.03), respectively.
CONCLUSIONS: Time-cumulated exposure to elevated blood pressure was significantly
associated with an elevated incidence of impaired glucose tolerance and diabetes.

DOI: 10.1186/s12872-017-0537-y
PMCID: PMC5414153
254. Nano Rev Exp. 2017 Jun 25;8(1):1341758. doi: 10.1080/20022727.2017.1341758.
eCollection 2017.
Transgene and islet cell delivery systems using nano-sized carriers for the
treatment of diabetes mellitus.
Ito K(1), Ookawara S(1), Ishibashi K(2), Morishita Y(1).
Author information:
(1)Division of Nephrology, First Department of Integrated Medicine, Saitama
Medical Center, Jichi Medical University, Saitama, Japan.
(2)Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo,
Japan.
Gene therapy that targets the pancreas and intestines with delivery systems using
nano-sized carriers such as viral and non-viral vectors could improve the control
of blood glucose levels, resulting in an improved prognosis for patients with
diabetes mellitus. Allogenic pancreatic islet cell transplantations using such
delivery systems have been developed as therapeutic options for diabetes
mellitus. This review focuses on transgenes and islet cell delivery systems using
nano-sized carriers for the treatment of diabetes mellitus.
DOI: 10.1080/20022727.2017.1341758
PMCID: PMC6167029
PMID: 30410709
255. Diabetes Educ. 2017 Jun;43(3):311-323. doi: 10.1177/0145721717701579. Epub 2017
Apr 21.
Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A
Diabetes Educator/Expert Prescriber Team Approach.
Bergen PM(1), Kruger DF(2), Taylor AD(3), Eid WE(1)(4)(5)(6), Bhan A(2), Jackson
JA(3).
Author information:
(1)St Elizabeth Physicians Regional Diabetes Center, Covington, Kentucky (Ms
Bergen, Dr Eid).
(2)Henry Ford Health System, Detroit, Michigan (Ms Kruger, Dr Bhan).
(3)Lilly Diabetes, Lilly USA, LLC, Indianapolis, Indiana (Mrs Taylor, Dr
Jackson).
(4)University of Kentucky College of Medicine, Lexington, Kentucky (Dr Eid).
(5)University of South Dakota Sanford School of Medicine, Sioux Falls, South
Dakota (Dr Eid).
(6)University of Alexandria, Egypt (Dr Eid).
Purpose The purpose of this article is to provide recommendations to the diabetes
educator/expert prescriber team for the use of human regular U-500 insulin
(U-500R) in patients with severely insulin-resistant type 2 diabetes, including
its initiation and titration, by utilizing dosing charts and teaching materials
translated from a recent U-500R clinical trial. Conclusions Clinically relevant
recommendations and teaching materials for the optimal use and management of
U-500R in clinical practice are provided based on the efficacy and safety results
of and lessons learned from the U-500R clinical trial by Hood et al, current
standards of practice, and the authors' clinical expertise. This trial was the
first robustly powered, randomized, titration-to-target trial to compare

twice-daily and three-times-daily U-500R dosing regimens. Modifications were made
to the initiation and titration dosing algorithms used in this trial to simplify
dosing strategies for the clinical setting and align with current glycemic
targets recommended by the American Diabetes Association. Leveraging the
expertise, resources, and patient interactions of the diabetes educator who can
provide diabetes self-management education and support in collaboration with the
multidisciplinary diabetes team is strongly recommended to ensure patients
treated with U-500R receive the timely and comprehensive care required to safely
and effectively use this highly concentrated insulin.
DOI: 10.1177/0145721717701579
PMCID: PMC5439542
256. JAMA Neurol. 2017 Nov 1;74(11):1345-1351. doi: 10.1001/jamaneurol.2017.1964.
Trends in Dementia Incidence in a Birth Cohort Analysis of the Einstein Aging
Study.
Derby CA(1)(2), Katz MJ(1), Lipton RB(1)(2), Hall CB(1)(2).
Author information:
(1)Saul R. Korey Department of Neurology, Albert Einstein College of Medicine,
Bronx, New York.
(2)Department of Epidemiology and Population Health, Albert Einstein College of
Medicine, Bronx, New York.
Importance: Trends in dementia incidence rates have important implications for
planning and prevention. To better understand incidence trends over time requires
separation of age and cohort effects, and few prior studies have used this
approach.
Objectives: To examine trends in dementia incidence and concomitant trends in
cardiovascular comorbidities among individuals aged 70 years or older who were
enrolled in the Einstein Aging Study between 1993 and 2015.
Design, Setting, and Participants: In this birth cohort analysis of all-cause
dementia incidence in persons enrolled in the Einstein Aging Study from October
20, 1993, through November 17, 2015, a systematically recruited, population-based
sample of 1348 participants from Bronx County, New York, who were 70 years or
older without dementia at enrollment and at least one annual follow-up was
studied. Poisson regression was used to model dementia incidence as a function of
age, sex, educational level, race, and birth cohort, with profile likelihood used
to identify the timing of significant increases or decreases in incidence.
Exposures: Birth year and age.
Main Outcomes and Measures: Incident dementia defined by consensus case
conference based on annual, standardized neuropsychological and neurologic
examination findings, using criteria from the DSM-IV.
Results: Among 1348 individuals (mean [SD] baseline age, 78.5 [5.4] years; 830
[61.6%] female; 915 [67.9%] non-Hispanic white), 150 incident dementia cases
developed during 5932 person-years (mean [SD] follow-up, 4.4 [3.4] years).
Dementia incidence decreased in successive birth cohorts. Incidence per 100
person-years was 5.09 in birth cohorts before 1920, 3.11 in the 1920 through 1924
birth cohorts, 1.73 in the 1925 through 1929 birth cohorts, and 0.23 in cohorts
born after 1929. Change point analyses identified a significant decrease in
dementia incidence among those born after July 1929 (95% CI, June 1929 to January
1930). The relative rate for birth cohorts before July 1929 vs after was 0.13
(95% CI, 0.04-0.41). Prevalence of stroke and myocardial infarction decreased
across successive birth cohorts, whereas diabetes prevalence increased.
Adjustment for these cardiovascular comorbidities did not explain the decreased
dementia incidence rates for more recent birth cohorts.
Conclusions and Relevance: Analyses confirm decreasing dementia incidence in this
population-based sample. Whether decreasing incidence will contribute to reduced

burden of dementia given the aging of the population is not known.
DOI: 10.1001/jamaneurol.2017.1964
PMCID: PMC5710583
257. Int J Epidemiol. 2017 Oct 1;46(5):1421-1432. doi: 10.1093/ije/dyx078.
Trends in obesity and diabetes across Africa from 1980 to 2014: an analysis of
pooled population-based studies.
NCD Risk Factor Collaboration (NCD-RisC) – Africa Working Group.
Collaborators: Kengne AP, Bentham J, Zhou B, Peer N, Matsha TE, Bixby H, Di
Cesare M, Hajifathalian K, Lu Y, Taddei C, Bovet P, Kyobutungi C, Agyemang C,
Aounallah-Skhiri H, Assah FK, Barkat A, Romdhane HB, Chan Q, Chaturvedi N,
Damasceno A, Delisle H, Delpeuch F, Doua K, Egbagbe EE, Ati JE, Elliott P,
Engle-Stone R, Erasmus RT, Fouad HM, Gareta D, Gureje O, Hendriks ME, Houti L,
Ibrahim MM, Kemper HCG, Killewo J, Kowlessur S, Kruger HS, Laamiri FZ, Laid Y,
Levitt NS, Lunet N, Magliano DJ, Maire B, Martin-Prevel Y, Mediene-Benchekor S,
Mohamed MK, Mondo CK, Monyeki KD, Mostafa A, Nankap M, Owusu-Dabo E, Rinke de Wit
TF, Saidi O, Schultsz C, Schutte AE, Senbanjo IO, Shaw JE, Smeeth L, Sobngwi E,
Jérome CS, Stronks K, Tanser F, Tchibindat F, Traissac P, Tshepo L, Tullu F,
Ukoli FAM, Viswanathan B, Wade AN, Danaei G, Stevens GA, Riley LM, Ezzati M,
Mbanya JCN.
Background: The 2016 Dar Es Salaam Call to Action on Diabetes and Other
non-communicable diseases (NCDs) advocates national multi-sectoral NCD strategies
and action plans based on available data and information from countries of
sub-Saharan Africa and beyond. We estimated trends from 1980 to 2014 in

age-standardized mean body mass index (BMI) and diabetes prevalence in these
countries, in order to assess the co-progression and assist policy formulation.
Methods: We pooled data from African and worldwide population-based studies which
measured height, weight and biomarkers to assess diabetes status in adults
aged ≥ 18 years. A Bayesian hierarchical model was used to estimate trends by sex
for 200 countries and territories including 53 countries across five African
regions (central, eastern, northern, southern and western), in mean BMI and
diabetes prevalence (defined as either fasting plasma glucose of ≥ 7.0 mmol/l,
history of diabetes diagnosis, or use of insulin or oral glucose control agents).
Results: African data came from 245 population-based surveys (1.2 million
participants) for BMI and 76 surveys (182 000 participants) for diabetes
prevalence estimates. Countries with the highest number of data sources for BMI
were South Africa (n = 17), Nigeria (n = 15) and Egypt (n = 13); and for diabetes
estimates, Tanzania (n = 8), Tunisia (n = 7), and Cameroon, Egypt and South
Africa (all n = 6). The age-standardized mean BMI increased from 21.0 kg/m2 (95%
credible interval: 20.3-21.7) to 23.0 kg/m2 (22.7-23.3) in men, and from
21.9 kg/m2 (21.3-22.5) to 24.9 kg/m2 (24.6-25.1) in women. The age-standardized
prevalence of diabetes increased from 3.4% (1.5-6.3) to 8.5% (6.5-10.8) in men,
and from 4.1% (2.0-7.5) to 8.9% (6.9-11.2) in women. Estimates in northern and
southern regions were mostly higher than the global average; those in central,
eastern and western regions were lower than global averages. A positive
association (correlation coefficient ≃ 0.9) was observed between mean BMI and
diabetes prevalence in both sexes in 1980 and 2014.
Conclusions: These estimates, based on limited data sources, confirm the rapidly
increasing burden of diabetes in Africa. This rise is being driven, at least in
part, by increasing adiposity, with regional variations in observed trends.
African countries' efforts to prevent and control diabetes and obesity should
integrate the setting up of reliable monitoring systems, consistent with the
World Health Organization's Global Monitoring System Framework.
© The Author 2017. Published by Oxford University Press on behalf of the

International Epidemiological Association
DOI: 10.1093/ije/dyx078
PMCID: PMC5837192
258. Diabetol Metab Syndr. 2016 Oct 13;8:70. eCollection 2016.
Trends in the prevalence of self-reported diabetes in Brazilian capital cities
and the Federal District, 2006-2014.
Iser BP(1), Vigo Á(2), Duncan BB(2), Schmidt MI(2).
Author information:
(1)Post Graduate Program in Epidemiology, School of Medicine, Universidade
Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600/414, Porto Alegre, RS
90035-003 Brazil ; Faculty of Medicine, Universidade do Sul de Santa Catarina,
Tubarão, Brazil.
(2)Post Graduate Program in Epidemiology, School of Medicine, Universidade
Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600/414, Porto Alegre, RS
90035-003 Brazil.
BACKGROUND: Diabetes is increasing globally, particularly in low and middle
income countries, posing a great challenge to health systems. Brazil is currently
ranked 4th in the world in terms of the absolute number of persons with diabetes.
Our aim was to analyze the trend in self-reported diabetes prevalence between
2006 and 2014 in Brazilian adults.
METHODS: We used data from the national telephone survey-VIGITEL. Over 40,000
individuals from probabilistic sample of subjects ≥18 years old residing in 26
state capitals and the Federal District were interviewed per year in each
location. Estimates were weighted to represent the surveyed population. We
analyzed trends with a linear regression model. We adjusted prevalence with a
probability predictive margins model, using as reference categories: men,
18-24 years, ≥12 years of schooling and lean/normal weight.
RESULTS: From 2006 to 2014, the overall prevalence increased from 5.5 to 8.0 %, a
net rise of 0.26 %/year (P = 0.001). After adjustment for sex, age, schooling and
BMI categories, the trend decreased only slightly to 0.25 %/year. Relatively
greater adjusted increases were present in men (0.28 %/year), in those ≥65 years
(0.52 %/year), with ≤8 years of schooling (0.33 %/year) and in those overweight
(0.24 %/year). The most consistent upward trends were observed among men
(coefficient of determination, R2 = 0.93), those with educational attainment of
0-8 years (R2 = 0.81), those > 65 years (R2 = 0.79) and those who were overweight
(R2 = 0.75). There was no significant trend in diabetes prevalence for the obese.
As expected, the prevalence of self-reported diabetes was always higher among
those with greater age, less schooling, in women, and in those with obesity.
Being obese was associated with having more than twice the prevalence of diabetes
of those normal/underweight.
CONCLUSIONS: Prevalence of self-reported diabetes in Brazilian adults has risen
between 2006 and 2014, especially among those 65 years or older, even after
taking into account the sociodemographic and nutritional changes during the
period. Regardless of possible causes (higher incidence, increased diagnosis or
decreased mortality), this increase in prevalence has enormous implications for
the health system, representing >300,000 newly diagnosed cases of diabetes yearly
requiring health care.
DOI: 10.1186/s13098-016-0185-x
PMCID: PMC5064973
PMID: 27757172
259. Trials. 2017 Nov 17;18(1):551. doi: 10.1186/s13063-017-2288-6.

Trial to Incentivise Adherence for Diabetes (TRIAD): study protocol for a
randomised controlled trial.
Bilger M(1), Shah M(2), Tan NC(2), Howard KL(3), Xu HY(2), Lamoureux EL(4),
Finkelstein EA(3)(5).
Author information:
(1)Health Services and Systems Research, Duke-NUS Medical School, 8 College Road,
169857, Singapore, Singapore. marcel.bilger@duke-nus.edu.sg.
(2)SingHealth Polyclinics, Singapore, Singapore.
(3)Health Services and Systems Research, Duke-NUS Medical School, 8 College Road,
169857, Singapore, Singapore.
(4)Singapore Eye Research Institute, Singapore National Eye Centre, Singapore,
Singapore.
(5)Duke Global Health Institute, Duke University, Durham, NC, USA.
BACKGROUND: Many people with diabetes have suboptimal glycaemic control due to
not being adherent to their treatment regimen. Behavioural economic theory
suggests that the lack of adherence results from the disconnect between the
timing of when costs and benefits accrue. One strategy to address this
discontinuity is to offer patients a near-term benefit, such as a financial
reward. Whereas there is evidence that rewards can improve treatment adherence
and sometimes health outcomes, further research is needed to determine whether
rewards are more effective when targeting processes or intermediary health
outcomes. In the Trial to Incentivise Adherence for Diabetes (TRIAD) we test
whether adding financial incentives to usual care can improve HbA1c levels among
people with diabetes and whether the financial incentives work better when
targeting processes (adherence to blood glucose testing, medication, and daily
physical activity) or the primary intermediary health outcome of self-monitored
blood glucose within an acceptable range.

METHODS/DESIGN: TRIAD is a randomised, controlled, open-label, single-centre
superiority trial with three parallel arms. A total of 240 patients with
suboptimally controlled diabetes (HbA1c ≥ 8%) from a polyclinic in Singapore are
block-randomised (blocking factor: current vs. new glucometer users) into three
arms, namely (1) usual care (UC) only, (2) UC with process incentive and (3) UC
with outcome incentive, in a 2:3:3 ratio. Masking the arm allocation will be
precluded by the behavioural nature of the intervention but blocking size will
not be disclosed to protect concealment. The primary outcome (change in HbA1c
level at month 6) will be measured by a laboratory that is independent from the
study team. Secondary outcomes (at month 6) include the number of blood glucose
testing days, glucose readings within the normal range (between 4 to 7 mmol/L),
medication-adherent days, physically active days, and average incentives earned
and time spent administrating the incentives.
DISCUSSION: This study will provide evidence on whether financial incentives can
cost-effectively improve glycaemic control. It will also provide evidence on the
benefit incidence of interventions involving financial incentives. By comparing
process to outcome incentives, this study will inform the design of future
incentive strategies in chronic disease management and beyond.
TRIAL REGISTRATION: ClinicalTrials.gov registry, ID: NCT02224417 . Registered on
22 August 2014.
DOI: 10.1186/s13063-017-2288-6
PMCID: PMC5693491
260. Diabetes Metab Syndr Obes. 2017 Aug 29;10:363-374. doi: 10.2147/DMSO.S145152.
eCollection 2017.
Type 2 diabetes in Vietnam: a cross-sectional, prevalence-based cost-of-illness
study.
Le NTD(1), Dinh Pham L(1), Quang Vo T(1).
Author information:
(1)Department of Pharmacy Administration, Faculty of Pharmacy, University of
Medicine and Pharmacy at Ho Chi Minh City, Vietnam.
BACKGROUND: According to the International Diabetes Federation, total global
health care expenditures for diabetes tripled between 2003 and 2013 because of
increases in the number of people with diabetes as well as in the average
expenditures per patient. This study aims to provide accurate and timely
information about the economic impacts of type 2 diabetes mellitus (T2DM) in
Vietnam.
METHOD: The cost-of-illness estimates followed a prospective, prevalence-based
approach from the societal perspective of T2DM with 392 selected diabetic
patients who received treatment from a public hospital in Ho Chi Minh City,
Vietnam, during the 2016 fiscal year.
RESULTS: In this study, the annual cost per patient estimate was US $246.10 (95%
CI 228.3, 267.2) for 392 patients, which accounted for about 12% (95% CI 11, 13)
of the gross domestic product per capita in 2017. That includes US $127.30, US
$34.40 and US $84.40 for direct medical costs, direct nonmedical expenditures,
and indirect costs, respectively. The cost of pharmaceuticals accounted for the
bulk of total expenditures in our study (27.5% of total costs and 53.2% of direct
medical costs). A bootstrap analysis showed that female patients had a higher
cost of treatment than men at US $48.90 (95% CI 3.1, 95.0); those who received
insulin and oral antidiabetics (OAD) also had a statistically significant higher
cost of treatment compared to those receiving OAD, US $445.90 (95% CI 181.2,
690.6). The Gradient Boosting Regression (Ensemble method) and Lasso Regression
(Generalized Linear Models) were determined to be the best models to predict the
cost of T2DM (R2=65.3, mean square error [MSE]=0.94; and R2=64.75, MSE=0.96,
respectively).
CONCLUSION: The findings of this study serve as a reference for policy decision
making in diabetes management as well as adjustment of costs for patients in
order to reduce the economic impact of the disease.
DOI: 10.2147/DMSO.S145152
PMCID: PMC5587014
PMID: 28919795
261. BMC Complement Altern Med. 2017 Feb 16;17(1):114. doi: 10.1186/s12906-017-1627-1.
UP601, a standardized botanical composition composed of Morus alba, Yerba mate
and Magnolia officinalis for weight loss.
Yimam M(1), Jiao P(2), Hong M(2), Brownell L(2), Lee YC(3), Hyun EJ(3), Kim
HJ(3), Nam JB(3), Kim MR(3), Jia Q(2).
Author information:
(1)Unigen, Inc., 3005 1st Avenue, Seattle, WA, 98121, USA. myimam@unigen.net.
(2)Unigen, Inc., 3005 1st Avenue, Seattle, WA, 98121, USA.
(3)Unigen, Inc., #450-86, Maebong-Ro, Dongnam-Gu, Cheonan-Si, Chungnam, 330-863,
Korea.
BACKGROUND: The prevalence of obesity is surging in an alarming rate all over the
world. Pharmaceutical drugs are considered potential adjunctive therapy to
lifestyle modification. However, for most, besides being too expensive, their
long term usages are hindered by their severe adverse effects. Here we describe
the effect of UP601, a standardized blend of extracts from Morus alba, Yerba mate
and Magnolia officinalis, in modulating a number of obesity-related phenotypic
and biochemical markers in a high-fat high-fructose (HFF)-induced C57BL/6J mouse
model of obesity.
METHOD: Adipogenesis activity of the composition was assessed in 3T3-L1 cells in
vitro. Effects of UP601 on body weight and metabolic markers were evaluated. It
was administered at oral doses of 300 mg/kg, 450 mg/kg and 600 mg/kg for 7 weeks.
Orlistat (40 mg/kg/day) was used as a positive control. Body compositions of mice
were assessed using dual energy X-ray absorptiometry (DEXA). Serum biomarkers
were measured for liver function and lipid profiling. Relative organ weights were
determined. Histopathological analysis was performed for non-alcoholic
steatohepatitis (NASH) scoring.
RESULTS: UP601 at 250 μg/ml resulted in 1.8-fold increase in lipolysis.
Statistically significant changes in body weight (decreased by 9.1, 19.6 and
25.6% compared to the HFF group at week-7) were observed for mice treated with
UP601 at 300, 450 and 600 mg/kg, respectively. Reductions of 9.1, 16.9, and 18.6%
in total cholesterol; 45.0, 55.0, 63.6% in triglyceride; 34.8, 37.1 and 41.6% in
LDL; 3.2, 21.6 (P = 0.03) and 33.7% (P = 0.005) in serum glucose were observed
for UP601 at 300, 450 and 600 mg/kg, respectively. Body fat distribution was
found reduced by 31.6 and 17.2% for the 450 mg/kg UP601 and orlistat,
respectively, from the DEXA scan analysis. Up to an 89.1% reduction in mesenteric
fat deposit was observed for UP601 in relative organ weight. Statistically
significant improvements in NASH scores were observed for mice treated with
UP601.
CONCLUSION: UP601, a standardized botanical composition from Morus alba, Yerba
mate and Magnolia officinalis could potentially be used for achieving healthy
weight loss and maintenance.
DOI: 10.1186/s12906-017-1627-1
PMCID: PMC5314713

262. BMC Public Health. 2016 Dec 5;16(1):1225.
Urban-rural differences in the prevalence of non-communicable diseases risk
factors among 25-74 years old citizens in Yangon Region, Myanmar: a cross
sectional study.
Htet AS(1)(2), Bjertness MB(3), Sherpa LY(3), Kjøllesdal MK(3), Oo WM(4), Meyer
HE(3), Stigum H(3), Bjertness E(3).
Author information:
Society, Faculty of Medicine, University of Oslo, Oslo, Norway. aungsh@gmail.com.
(2)International Relations Division, Ministry of Health, Nay Pyi Taw, Myanmar.
aungsh@gmail.com.
Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
(4)Faculty of Medicine, SEGi University, Petaling Jaya, Malaysia.
BACKGROUND: Recent societal and political reforms in Myanmar may upturn the
socio-economy and, thus, contribute to the country's health transition. Baseline
data on urban-rural disparities in non-communicable disease (NCD) risk factors
are not thoroughly described in this country which has been relatively closed for
more than five decades. We aim to investigate urban-rural differences in mean
values and the prevalence of selected behavioral and metabolic risk factors for
non-communicable diseases and 10-years risk in development of coronary heart
diseases (CHD).
METHODS: Two cross-sectional studies were conducted in urban and rural areas of
Yangon Region in 2013 and 2014 respectively, using the WHO STEPwise approach to
surveillance of risk factors of NCDs. Through a multi-stage cluster sampling
method, 1486 participants were recruited.

RESULTS: Age-standardized prevalence of the behavioral risk factors tended to be
higher in the rural than urban areas for all included factors and significantly
higher for alcohol drinking (19.9% vs. 13.9%; p = 0.040) and low fruit &
vegetable consumption (96.7% vs. 85.1%; p = 0.001). For the metabolic risk
factors, the tendency was opposite, with higher age-standardized prevalence
estimates in urban than rural areas, significantly for overweight and obesity
combined (40.9% vs. 31.2%; p = 0.023), obesity (12.3% vs.7.7%; p = 0.019) and
diabetes (17.2% vs. 9.2%; p = 0.024). In sub-group analysis by gender, the
prevalence of hypercholesterolemia and hypertriglyceridemia were significantly
higher in urban than rural areas among males, 61.8% vs. 40.4%; p = 0.002 and
31.4% vs. 20.7%; p = 0.009, respectively. Mean values of age-standardized
metabolic parameters showed higher values in urban than rural areas for both male
and female. Based on WHO age-standardized Framingham risk scores, 33.0% (95%
CI = 31.7-34.4) of urban dwellers and 27.0% (95% CI = 23.5-30.8) of rural
dwellers had a moderate to high risk of developing CHD in the next 10 years.
CONCLUSION: The metabolic risk factors, as well as a moderate or high ten-year
risk of CHD were more common among urban residents whereas behavioral risk
factors levels were higher in among the rural people of Yangon Region. The high
prevalences of NCD risk factors in both urban and rural areas call for preventive
measures to reduce the future risk of NCDs in Myanmar.
DOI: 10.1186/s12889-016-3882-3
PMCID: PMC5139102
263. J Med Internet Res. 2018 Feb 20;20(2):e55. doi: 10.2196/jmir.9230.
Users, Uses, and Effects of Social Media in Dietetic Practice: Scoping Review of
the Quantitative and Qualitative Evidence.

Dumas AA(#)(1), Lapointe A(#)(1), Desroches S(#)(1).
Author information:
(1)Institute of Nutrition and Functional Foods, School of Nutrition, Laval
BACKGROUND: Social media platforms are increasingly used by registered dietitians
(RDs) to improve knowledge translation and exchange in nutrition. However, a
thorough understanding of social media in dietetic practice is lacking.
OBJECTIVE: The objective of this study was to map and summarize the evidence
about the users, uses, and effects of social media in dietetic practice to
identify gaps in the literature and inform future research by using a scoping
review methodology.
METHODS: Stages for conducting the scoping review included the following: (1)
identifying the research question; (2) identifying relevant studies through a
comprehensive multidatabase and gray literature search strategy; (3) selecting
eligible studies; (4) charting the data; and (5) collating, summarizing, and
reporting results for dissemination. Finally, knowledge users (RDs working for
dietetic professional associations and public health organizations) were involved
in each review stage to generate practical findings.
RESULTS: Of the 47 included studies, 34 were intervention studies, 4 were
descriptive studies, 2 were content analysis studies, and 7 were expert opinion
papers in dietetic practice. Discussion forums were the most frequent social
media platform evaluated (n=19), followed by blogs (n=13) and social networking
sites (n=10). Most studies targeted overweight and obese or healthy users, with
adult populations being most studied. Social media platforms were used to deliver
content as part of larger multiple component interventions for weight management.
Among intervention studies using a control group with no exposition to social
media, we identified positive, neutral, and mixed effects of social media for
outcomes related to users' health behaviors and status (eg, dietary intakes and
body weight), participation rates, and professional knowledge. Factors associated
with the characteristics of the specific social media, such as ease of use, a
design for quick access to desired information, and concurrent reminders of use,
were perceived as the main facilitators to the use of social media in dietetic
practice, followed to a lesser extent by interactions with an RD and social
support from fellow users. Barriers to social media use were mostly related to
complicated access to the site and time issues.
CONCLUSIONS: Research on social media in dietetic practice is at its infancy, but
it is growing fast. So far, this field of research has targeted few social media
platforms, most of which were assessed in multiple-component interventions for
weight management among overweight or obese adults. Trials isolating the effects
and mechanisms of action of specific social media platforms are needed to draw
conclusions regarding the effectiveness of those tools to support dietetic
practice. Future studies should address barriers and facilitators related to the
use of social media written by RDs and should explore how to make these tools
useful for RDs to reach health consumers to improve health through diet.
©Audrée-Anne Dumas, Annie Lapointe, Sophie Desroches. Originally published in the
Journal of Medical Internet Research (http://www.jmir.org), 20.02.2018.
DOI: 10.2196/jmir.9230
PMCID: PMC5840482
PMID: 29463487
264. Diabetes Care. 2018 Jul;41(7):1438-1447. doi: 10.2337/dc18-0181. Epub 2018 Apr
24.
Using Indirect Measures to Identify Geographic Hot Spots of Poor Glycemic
Control: Cross-sectional Comparisons With an A1C Registry.

Lee DC(1)(2), Jiang Q(3), Tabaei BP(3), Elbel B(4)(5), Koziatek CA(4), Konty
KJ(3), Wu WY(3).
Author information:
(1)Ronald O. Perelman Department of Emergency Medicine, New York University
School of Medicine, New York, NY david.lee@nyumc.org.
(2)Department of Population Health, New York University School of Medicine, New
York, NY.
(3)New York City Department of Health and Mental Hygiene, New York, NY.
(4)Ronald O. Perelman Department of Emergency Medicine, New York University
School of Medicine, New York, NY.
(5)Wagner Graduate School of Public Service, New York University, New York, NY.
OBJECTIVE: Focusing health interventions in places with suboptimal glycemic
control can help direct resources to neighborhoods with poor diabetes-related
outcomes, but finding these areas can be difficult. Our objective was to use
indirect measures versus a gold standard, population-based A1C registry to
identify areas of poor glycemic control.
RESEARCH DESIGN AND METHODS: Census tracts in New York City (NYC) were
characterized by race, ethnicity, income, poverty, education, diabetes-related
emergency visits, inpatient hospitalizations, and proportion of adults with
diabetes having poor glycemic control, based on A1C >9.0% (75 mmol/mol). Hot spot
analyses were then performed, using the Getis-Ord Gi* statistic for all measures.
We then calculated the sensitivity, specificity, positive and negative predictive
values, and accuracy of using the indirect measures to identify hot spots of poor
glycemic control found using the NYC A1C Registry data.
RESULTS: Using A1C Registry data, we identified hot spots in 42.8% of 2,085 NYC
census tracts analyzed. Hot spots of diabetes-specific inpatient
hospitalizations, diabetes-specific emergency visits, and age-adjusted diabetes
prevalence estimated from emergency department data, respectively, had 88.9%,
89.6%, and 89.5% accuracy for identifying the same hot spots of poor glycemic
control found using A1C Registry data. No other indirect measure tested had
accuracy >80% except for the proportion of minority residents, which had 86.2%
accuracy.
CONCLUSIONS: Compared with demographic and socioeconomic factors, health care
utilization measures more accurately identified hot spots of poor glycemic
control. In places without a population-based A1C registry, mapping
diabetes-specific health care utilization may provide actionable evidence for
targeting health interventions in areas with the highest burden of uncontrolled
diabetes.
DOI: 10.2337/dc18-0181
265. Dement Geriatr Cogn Dis Extra. 2016 Dec 5;6(3):541-548. doi: 10.1159/000450784.
eCollection 2016 Sep-Dec.
The Utility of the Mini-Addenbrooke's Cognitive Examination as a Screen for
Cognitive Impairment in Elderly Patients with Chronic Kidney Disease and
Diabetes.
Hobson P(1), Rohoma KH(2), Wong SP(1), Kumwenda MJ(1).
Author information:
(1)Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, NHS Wales,
Bodelwyddan, UK.
(2)Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, NHS Wales,
Bodelwyddan, UK; Internal Medicine Department, Faculty of Medicine, Alexandria

University, Alexandria, Egypt.
BACKGROUND/AIMS: We tested the utility of the Mini-Addenbrooke's Cognitive
Examination (M-ACE) in a cohort of older adults with chronic kidney disease (CKD)
and diabetes.
METHOD: The M-ACE was administered to 112 CKD and diabetes patients attending a
nephrology clinic. Cognitive impairment was based upon patient, informant, and
case review, neuropsychological assessment, and application of criteria for mild
cognitive impairment (MCI) and the Diagnostic and Statistical Manual of Mental
Disorders, fifth edition for dementia. The M-ACE was also compared to the
Mini-Mental State Examination (MMSE).
RESULTS: Upon assessment, 52 patients had normal cognitive function, 33 had MCI,
and 27 had dementia. The area under the receiver operating curve for the M-ACE
was 0.96 (95% CI 0.95-1.00). The sensitivity and specificity for a dementia
diagnosis were 0.96 and 0.84 at the cut point <25 and 0.70 and 1.00 at the cut
point <21. Mean M-ACE scores differed significantly between normal, demented, and
MCI groups (p < 0.001), and compared to the MMSE, the M-ACE did not suffer from
ceiling effects.
CONCLUSION: The M-ACE is an easily administered test with good sensitivity and
specificity to capture and assist in the diagnosis of MCI or dementia in patients
with CKD and diabetes.
DOI: 10.1159/000450784
PMCID: PMC5216187
PMID: 28101100
Conflict of interest statement: The authors in this investigation do not have a
have any disclosures.

eCollection 2018.
Validation of DIABSCORE in screening for Type 2 Diabetes and prediabetes in
Tunisian population.
Gannar F(1)(2), Rodriguez-Pérez MDC(2), Domínguez Coello S(2)(3), Haouet K(4),
Brito Díaz B(2), Cabrera de León A(2)(5).
Author information:
(1)Research Unit 'Integrated Physiology', Laboratory of Biochemistry-Human
Nutrition, Faculty of Sciences of Bizerte, UR11ES33 Carthage University, Tunis,
Tunisia.
(2)Primary Care Research Unit and University Hospital Nuestra Señora de
Candelaria, Tenerife, Spain.
(3)La Victoria Health Center, Tenerife, Spain.
(4)Laboratory of Biochemical Analysis, University Hospital Mohamed Taher
Maamouri, Nabeul, Tunisia.
(5)Department of Preventive Medicine, La Laguna University, Tenerife, Spain.
AIMS: To perform a validation of DIABSCORE in a sample of Tunisian adults and
find out the optimal cut-off point for screening of Type 2 diabetes (T2D) and
prediabetes.
METHODS: 225 adults 18-75 years and a subgroup of 138 adults (18-54 years), with
undiagnosed T2D from the region of Cap-Bon, Tunisia were included in the present
study. The DIABSCORE was calculated based on: age, waist/height ratio, family
history of T2D and gestational diabetes. Receiver operating characteristics (ROC)
curves and areas under curve (AUC) were obtained. The T2D and prediabetes
prevalences odds ratios (OR) between patients exposed and not exposed to
DIABSCORE≥90 and DIABSCORE≥80, respectively were calculated in both age ranges.
RESULTS: For screening of T2D the best value was DIABSCORE = 90 with a highest
sensitivity (Se), negative predictive value (NPV) and lower negative likelihood
ratio in participants aged 18-75 yr (Se = 97%; NPV = 97%) when compared to
participants aged 18-54 yr (Se = 95%; NPV = 97%); for prediabetes, the best Se
and NPV were for DIABSCORE = 80 in both age groups, but it showed a disbalanced
sensitivity-specificity. The ROC curves for T2D showed a similar AUC in both age
ranges (AUC = 0.62 and AUC = 0.61 respectively). The ROC curves for prediabetes
showed a highest AUC in those aged 18-54 years than the older ones (AUC = 0.62
and AUC = 0.57, respectively). The prevalences OR of T2D for DIABSCORE≥90 was
higher than for DIABSCORE≥80 in both age ranges. Nevertheless, the prevalences OR
of prediabetes for DIABSCORE≥90 was half of the detected for DIABSCORE≥80 in both
age ranges.
CONCLUSION: The DIABSCORE is a simple clinical tool and accurate method in
screening for T2D and prediabetes in the adult Tunisian population.
PMCID: PMC6093602
PMID: 30110336
interests exist.
267. Public Health Nutr. 2018 Aug;21(12):2211-2220. doi: 10.1017/S1368980018000848.
Epub 2018 Apr 16.
Validity of an FFQ to measure nutrient and food intakes in Tanzania.
Zack RM(1), Irema K(2), Kazonda P(2), Leyna GH(2), Liu E(3), Gilbert S(3),
Lukmanji Z(4), Spiegelman D(1), Fawzi W(1), Njelekela M(5), Killewo J(2), Danaei
G(1).
Author information:
(1)1Department of Epidemiology,Harvard T.H. Chan School of Public Health,Kresge
Building,Room 911,677 Huntington Avenue,Boston,MA 02115,USA.
(2)2School of Public Health,Muhimbili University of Health and Allied
Sciences,Dar es Salaam,United Republic of Tanzania.
(3)3Department of Global Health and Population,Harvard T.H. Chan School of Public
Health,Boston,MA,USA.
(4)4Independent nutrition/dietetic consultant and consultant dietitian affiliated
with Tumaini Comprehensive Infirmary,Dar es Salaam,United Republic of Tanzania.
(5)7Department of Physiology,Muhimbili University of Health and Allied
Sciences,Dar es Salaam,United Republic of Tanzania.
OBJECTIVE: FFQ are often used to estimate food and nutrient intakes to rank
individuals by their level of intake. We evaluated the relative validity of a
semi-quantitative FFQ created for use in Tanzania by comparing it with two 24 h
diet recalls.
DESIGN: We measured relative validity of the FFQ with deattenuated
energy-adjusted rank correlations for nutrients, deattenuated rank correlations
for food groups, and performed a cross-classification analysis of energy-adjusted
nutrient quartiles using percentage of agreement and Bland-Altman analysis.
SETTING: Interviews were conducted in 2014 in participants' homes in Ukonga, Dar
es Salaam, Tanzania.
SUBJECTS: We surveyed 317 adults aged 40 years or older from the general public.
RESULTS: Deattenuated energy-adjusted rank correlation coefficients of nutrients
ranged from -0·03 for riboflavin to 0·41 for percentage of energy from
carbohydrates, with a median correlation of 0·21. Coefficients for food groups
ranged from 0·00 for root vegetables to 0·51 for alcohol, with a median of 0·35.
Relative to the average of the two 24 h diet recalls, the FFQ overestimated
energy intake and intakes of all nutrients and food groups, other than tea, with
ratios among nutrients ranging from 1·34 for SFA to 7·08 for vitamin A; and among
food groups from 0·92 for tea to 9·00 for fruit. The percentage of participants
classified into the same nutrient intake quartile ranged from 23 % for SFA to 32
% for both niacin and pantothenic acid, with a median of 28 %.
CONCLUSIONS: The FFQ performed moderately well in urban Tanzanian adults.
DOI: 10.1017/S1368980018000848
PMID: 29656731
268. J Family Med Prim Care. 2017 Apr-Jun;6(2):366-373. doi: 10.4103/2249-4863.220010.
Validity of Indian Diabetes Risk Score and its association with body mass index
and glycosylated hemoglobin for screening of diabetes in and around areas of
Lucknow.
Khan MM(1), Sonkar GK(2), Alam R(1), Mehrotra S(3), Khan MS(4), Kumar A(1),
Sonkar SK(5).
Author information:
(1)Department of Biochemistry, Integral Institute of Medical Sciences and
Research, Integral University, Lucknow, Uttar Pradesh, India.
(2)Department of Biochemistry, King George's Medical University, Lucknow, Uttar
Pradesh, India.
(3)Department of Medicine, Integral Institute of Medical Sciences and Research,
Integral University, Lucknow, Uttar Pradesh, India.
(4)Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
(5)Department of Medicine, Hemodialysis Unit, King George's Medical University,
Lucknow, Uttar Pradesh, India.
Objectives: The present study aimed to assess the validity of Indian Diabetes
Risk Score (IDRS) and its association with body mass index (BMI) and glycosylated
hemoglobin (HbA1c) for screening of diabetes and obesity.

Methodology: A cross-sectional study was designed, and samples were randomly
enrolled from Lucknow and its adjoining areas. Totally, 405 subjects were
included in the study. We used diabetes risk factors (age, waist circumference,
physical activity, and family history of diabetes) for screening of diabetes and
abdominal obesity (AO) and BMI for screening of general obesity. HbA1c was used
for confirming the diabetes patients in this population. Statistical analysis was
applied to all data using SPSS software (version 20.0). P < 0.05 was considered
statistically significant.
Results: All 405 subjects were assessed for diabetic risk factors, BMI, and
glycated hemoglobin. Of these, 56.3% subjects were aged ≥50 years. 1° and 2° AO
was found in 47.9% and 40% subjects, respectively. About 27.1% subjects were
found to have sedentary lifestyle, and 72.6% were found to have no family history
of diabetes. According to IDRS, 272 subjects (67.2%) were found at high risk of
diabetes (score ≥60). Based on BMI calculation, 198 subjects were obese, of which
79.3% were found at high risk for diabetes. A significant association was found
between subjects with higher risk score and BMI (P < 0.001). Assessment of HbA1c
showed that 97 (23.9%) were prediabetic and 204 (50.4%) were diabetic, of which
63.9% and 77%, respectively was at high risk for diabetes as per IDRS. A
significant association was found between subjects with higher risk score and
HbA1c (P < 0.001).
Conclusion: Our study fully supports the validity of IDRS, as it can be used as a
cost-effective tool for primary mass screening of diabetes. Moreover, its
combination with BMI value and HbA1c can be used for strict monitoring for
diabetes and obesity at primary health care centers to reduce the early
development of diabetes complications and severe obesity comorbidities.
DOI: 10.4103/2249-4863.220010
PMCID: PMC5749088
PMID: 29302549
Conflict of interest statement: There are no conflicts of interest.

269. Nutr Diabetes. 2018 Mar 9;8(1):12. doi: 10.1038/s41387-018-0022-4.
Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective
study.
Chiu THT(1)(2)(3), Pan WH(2)(4), Lin MN(5)(6), Lin CL(7)(8).
Author information:
(1)Department of Nutrition Therapy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi
Medical Foundation. No. 2, Min-Sheng Road, Dalin Town, Chiayi County, 622,
Taiwan.
(2)Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan
University, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan.
(3)Department of Medicine, College of Medicine, Tzu Chi University, Hualien,
Taiwan. No.701, Sec. 3, Chung Yang Road, Hualien, 970, Taiwan.
(4)Institute of Biomedical Sciences, Academia Sinica, Address: 128 Sec. 2,
Academia Road, Nankang, Taipei, 115, Taiwan.
(5)Department of Family Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi
Medical Foundation. No. 2, Min-Sheng Road, Dalin Town, Chiayi County, 622,
Taiwan. mingnan.lin@gmail.com.
(6)Department of Family Medicine, College of Medicine, Tzu Chi University,
Hualien, Taiwan. No.701, Sec. 3, Chung Yang Road, Hualien, 970, Taiwan.
mingnan.lin@gmail.com.
(7)Department of Internal Medicine, Hualien Tzu Chi Medical Center, Hualien,
Taiwan. No. 707, Sec. 3, Chung Yang Road, Hualien, 970, Taiwan.
(8)Department of Internal Medicine, College of Medicine, Tzu Chi University,
Hualien, Taiwan. No.701, Sec. 3, Chung Yang Road, Hualien, 970, Taiwan.
BACKGROUND/OBJECTIVES: Vegetarian diets are inversely associated with diabetes in

Westerners but their impact on Asians-whose pathophysiology differ from
Westerners-is unknown. We aim to investigate the association between a vegetarian
diet, change in dietary patterns and diabetes risk in a Taiwanese Buddhist
population.
METHODS: We prospectively followed 2918 non-smoking, non-alcohol drinking
Buddhists free of diabetes, cancer, and cardiovascular diseases at baseline, for
a median of 5 years, with 183 incident diabetes cases confirmed. Diet was
assessed through a validated food frequency questionnaire at baseline and a
simple questionnaire during follow-ups. Incident cases of diabetes were
ascertained through follow-up questionnaires, fasting glucose and HbA1C.
Stratified Cox Proportional Hazards Regression was used to assess the effect of
diets on risk of diabetes.
RESULTS: Consistent vegetarian diet was associated with 35% lower hazards (HR:
0.65, 95% CI: 0.46, 0.92), while converting from a nonvegetarian to a vegetarian
pattern was associated with 53% lower hazards (HR: 0.47, 95% CI: 0.30, 0.71) for
diabetes, comparing with nonvegetarians while adjusting for age, gender,
education, physical activity, family history of diabetes, follow-up methods, use
of lipid-lowering medications, and baseline BMI.
CONCLUSION: Vegetarian diet and converting to vegetarian diet may protect against
diabetes independent of BMI among Taiwanese.
DOI: 10.1038/s41387-018-0022-4
PMCID: PMC5856738
PMID: 29549240
270. Diabetes. 2017 Jul;66(7):1735-1741. doi: 10.2337/db17-0093.
We Know More Than We Can Tell About Diabetes and Vascular Disease: The 2016 Edwin
Bierman Award Lecture.

Semenkovich CF(1).
Author information:
(1)Division of Endocrinology, Metabolism and Lipid Research, Department of Cell
Biology and Physiology, Washington University School of Medicine in St. Louis,
St. Louis, MO csemenko@wustl.edu.
The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L.
Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes,
obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a
leading scientist in the field of macrovascular complications and contributing
risk factors in diabetes. Clay F. Semenkovich, MD, the Irene E. and Michael M.
Karl Professor and Chief of the Division of Endocrinology, Metabolism and Lipid
Research at Washington University School of Medicine in St. Louis, St. Louis, MO,
received the prestigious award at the American Diabetes Association's 76th
Scientific Sessions, 10-14 June 2016, in New Orleans, LA. He presented the Edwin
Bierman Award Lecture, "We Know More Than We Can Tell About Diabetes and Vascular
Disease," on Sunday, 12 June 2016.Diabetes is a disorder of abnormal lipid
metabolism, a notion strongly supported by the work of Edwin Bierman, for whom
this eponymous lecture is named. This abnormal lipid environment continues to be
associated with devastating vascular complications in diabetes despite current
therapies, suggesting that our understanding of the pathophysiology of blood
vessel disease in diabetes is limited. In this review, potential new insights
into the nature of diabetic vasculopathy will be discussed. Recent observations
suggest that while the concept of distinct macrovascular and microvascular
complications of diabetes has been useful, vascular diseases in diabetes may be
more interrelated than previously appreciated. Moreover, the intermediary
metabolic pathway of de novo lipogenesis, which synthesizes lipids from simple
precursors, is robustly sensitive to insulin and may contribute to these
complications. De novo lipogenesis requires fatty acid synthase, and recent
studies of this enzyme suggest that endogenously produced lipids are channeled to
specific intracellular sites to affect physiology. These findings raise the
possibility that novel approaches to treating diabetes and its complications
could be based on altering the intracellular lipid milieu.
DOI: 10.2337/db17-0093
PMCID: PMC5482089
271. BMJ Open. 2017 Sep 27;7(9):e016009. doi: 10.1136/bmjopen-2017-016009.
Web-based self-management support for people with type 2 diabetes
(HeLP-Diabetes): randomised controlled trial in English primary care.
Murray E(1), Sweeting M(2), Dack C(3), Pal K(1), Modrow K(1), Hudda M(4), Li
J(5), Ross J(1), Alkhaldi G(1), Barnard M(6), Farmer A(7), Michie S(8), Yardley
L(7)(9), May C(10), Parrott S(5), Stevenson F(1), Knox M(1), Patterson D(6).
Author information:
(1)Research Department of Primary Care and Population Health, University College
London, London, UK.
(2)Department of Public Health and Primary Care, Cardiovascular Epidemiology
Unit, University of Cambridge, Cambridge, UK.
(3)Department of Psychology, University of Bath, Bath, UK.
(4)Population Health Research Institute, St George's, University of London,
London, UK.
(5)Department of Health Sciences, University of York, York, UK.
(6)Whittington Health, London, UK.

Oxford, UK.
(8)Department of Clinical, Educational and Health Psychology, Centre for
Behaviour Change, University College London, London, UK.
(9)Department of Psychology, University of Southampton, Southampton, UK.
(10)Faculty of Health Sciences, University of Southampton, Southampton, UK.
OBJECTIVE: To determine the effectiveness of a web-based self-management
programme for people with type 2 diabetes in improving glycaemic control and
reducing diabetes-related distress.
METHODS AND DESIGN: Individually randomised two-arm controlled trial.
SETTING: 21 general practices in England.
PARTICIPANTS: Adults aged 18 or over with a diagnosis of type 2 diabetes
registered with participating general practices.
INTERVENTION AND COMPARATOR: Usual care plus either Healthy Living for People
with Diabetes (HeLP-Diabetes), an interactive, theoretically informed, web-based
self-management programme or a simple, text-based website containing basic
information only.
OUTCOMES AND DATA COLLECTION: Joint primary outcomes were glycated haemoglobin
(HbA1c) and diabetes-related distress, measured by the Problem Areas in Diabetes
(PAID) scale, collected at 3 and 12 months after randomisation, with 12 months
the primary outcome point. Research nurses, blind to allocation collected
clinical data; participants completed self-report questionnaires online.
ANALYSIS: The analysis compared groups as randomised (intention to treat) using a
linear mixed effects model, adjusted for baseline data with multiple imputation
of missing values.
RESULTS: Of the 374 participants randomised between September 2013 and December
2014, 185 were allocated to the intervention and 189 to the control. Final (12
month) follow-up data for HbA1c were available for 318 (85%) and for PAID 337
(90%) of participants. Of these, 291 (78%) and 321 (86%) responses were recorded
within the predefined window of 10-14 months. Participants in the intervention
group had lower HbA1c than those in the control (mean difference -0.24%; 95% CI
-0.44 to -0.049; p=0.014). There was no significant overall difference between
groups in the mean PAID score (p=0.21), but prespecified subgroup analysis of
participants who had been more recently diagnosed with diabetes showed a
beneficial impact of the intervention in this group (p = 0.004). There were no
reported harms.
CONCLUSIONS: Access to HeLP-Diabetes improved glycaemic control over 12 months.
TRIAL REGISTRATION NUMBER: ISRCTN02123133.
DOI: 10.1136/bmjopen-2017-016009
PMCID: PMC5623569
Conflict of interest statement: Competing interests: EM is the managing director
of a not-for-profit community interest company established to disseminate
HeLP-Diabetes across the NHS.
272. BMJ Open. 2017 Jun 8;7(5):e014684. doi: 10.1136/bmjopen-2016-014684.
Weight cycling and the subsequent onset of type 2 diabetes mellitus: 10-year
cohort studies in urban and rural Japan.
Yokomichi H(1), Ohde S(2), Takahashi O(2), Mochizuki M(3), Takahashi A(1), Yoda
Y(4), Tsuji M(4), Akiyama Y(1), Yamagata Z(1).
Author information:
(1)Department of Health Sciences, University of Yamanashi, Chuo City, Yamanashi,

Japan.
(2)Center for Clinical Epidemiology, St. Luke's International University, Chuo
Ward, Tokyo, Japan.
(3)Department of Pediatrics, University of Yamanashi, Chuo City, Yamanashi,
Japan.
(4)Yamanashi Koseiren Health Care Center, Kofu City, Yamanashi, Japan.
OBJECTIVE: To investigate how weight cycling (gaining and losing weight) affects
the risk of diabetes.
DESIGN: Cohort studies.
SETTING: Primary healthcare in urban and rural Japan.
PARTICIPANTS: 20 708 urban and 9670 rural residents.
PRIMARY OUTCOME MEASURES: ORs for diabetes in those with weight loss, weight
loss-gain, stable weight, weight gain-loss and weight gain over 10 years. Weight
gain and loss were defined as a change of more than ±4% from baseline weight.
RESULTS: In the urban region, the ORs relative to the stable group for the
loss-gain and gain-loss groups were 0.63 (95% CI 0.45 to 0.89) and 0.51 (95% CI
0.32 to 0.82) for men and 0.72 (95% CI 0.39 to 1.34) and 1.05 (95% CI 0.57 to
1.95) for women. In the rural region, they were 1.58 (95% CI 0.78 to 3.17) and
0.44 (95% CI 0.15 to 1.29) in men and 0.41 (95% CI 0.12 to 1.44) and 0.77 (95% CI
0.28 to 2.14) in women. The ORs for an increase in weight between 5 and 10 kg
from the age of 20 years were 1.54 (95% CI 1.03 to 2.30) in men and 0.96 (95% CI
0.55 to 1.65) in women.
CONCLUSIONS: In Japan, weight cycling was associated with a significant reduction
in the risk of diabetes for men from urban regions. The associations were unclear
for women from urban regions and both men and women from rural regions. These
results differ from those in Western studies, probably because of differences in
diet, insulin secretion and sensitivity and weight-consciousness.
DOI: 10.1136/bmjopen-2016-014684
PMCID: PMC5729995
273. Int J Telemed Appl. 2018 Feb 14;2018:3427389. doi: 10.1155/2018/3427389.
eCollection 2018.
What Kind of Information and Communication Technologies Do Patients with Type 2
Diabetes Mellitus Prefer? An Ecuadorian Cross-Sectional Study.
Chérrez-Ojeda I(1)(2), Vanegas E(1)(2), Calero E(2), Plaza K(2), Cano JA(1)(2),
Calderon JC(1)(2), Valdano J(1), Gutierrez JO(1), Guevara J(2).
Author information:
(1)Universidad Espíritu Santo, Samborondón, Ecuador.
(2)Respiralab Research Group, Respiralab, Guayaquil, Ecuador.
Purpose: The purpose of this study is to assess the frequency of use of
information and communication technologies and patterns of preference among
Ecuadorian patients with diabetes.
Methods: We conducted an anonymous cross-sectional survey on type 2 diabetes
mellitus. A chi-square test for association and adjusted regression analyses were
performed.
Results: 248 patients were enrolled, with a mean sample age of 57.7 years. SMS
was the most used ICT (66.0%). The Internet was used by 45.2% of patients to
obtain information about diabetes. SMS and email were rated as the most useful
ICTs for receiving information (64.5% and 28.1%, resp.) and asking physicians
about diabetes (63.8% and 26.1%, resp.). Patients were also interested in
receiving disease information (82.4%) and asking physicians about diabetes
(84.7%) through WhatsApp. Adjusted logistic regressions revealed that individuals
aged 55 years or younger, those with superior degree level, and those with long
diabetes history preferred email for receiving information and asking physicians
about diabetes compared to those above 55 years, those with low education level,
and those with short diabetes history, respectively.
Conclusion: Understanding preferences of ICTs among patients with diabetes could
facilitate application development targeted towards specific requirements from
patients.
DOI: 10.1155/2018/3427389
PMCID: PMC5832117
PMID: 29666639
274. BMC Public Health. 2017 Jan 31;17(1):133. doi: 10.1186/s12889-016-3999-4.
White rice intake and incidence of type-2 diabetes: analysis of two prospective
cohort studies from Iran.
Golozar A(1)(2), Khalili D(3), Etemadi A(1)(4), Poustchi H(1), Fazeltabar A(1),
Hosseini F(5), Kamangar F(6), Khoshnia M(7), Islami F(8), Hadaegh F(3), Brennan
P(9), Boffetta P(10), Abnet CC(4), Dawsey SM(4), Azizi F(11), Malekzadeh R(1),
Danaei G(12)(13)(14).
Author information:
(1)Digestive Disease Research Institute, Shariati Hospital, Tehran University of
Medical Sciences, Tehran, 14117, Iran.

Baltimore, MD, 21205, USA.
Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran,
17413, Iran.
(4)Division of Cancer Epidemiology and Genetics, National Cancer Institute,
Bethesda, MD, 20850, USA.
(5)Nutrition and Endocrine Research Center/Obesity Research Center,Research
Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science,
Tehran, 17413, Iran.
(6)School of Community Health and Policy, Morgan State University, Baltimore,
21251, MD, USA.
(7)Golestan Research Center of Gastroenterology and Hepatology, Golestan
University of Medical Sciences, Gorgan, Golestan, 0619, Iran.
(8)Surveillance and Health Services Research, American Cancer Society, Atlanta,
30303, Georgia, USA.
(9)International Agency for Research on Cancer, Lyon, 69008, France.
(10)The Tisch Cancer Institute and Institute for Translational Epidemiology,
Mount Sinai School of Medicine, New York, 10029, New York, USA.
Beheshti University of Medical Sciences, Tehran, 17413, Tehran, Iran.
677 Huntington Avenue, Bldg 1, Boston, 02115, MA, USA. gdanaei@hsph.harvard.edu.
(13)Department of Epidemiology, Harvard School of Public Health, 677 Huntington
Avenue, Bldg 1, Boston, MA, 02115, USA. gdanaei@hsph.harvard.edu.
(14)SAPHIR, the Scientific Association for Public Health in Iran , Boston, 02132,
USA. gdanaei@hsph.harvard.edu.
BACKGROUND: Refined grains and white rice have been associated with elevated risk
of type 2 diabetes mellitus (T2DM). In this study, we sought to quantify the
effect of white rice intake on incident T2DM in two prospective population-based
cohort studies from Iran, where white rice is one of the main staple.
METHODS: We used follow-up data from 9,182 participants from Golestan Cohort
Study (GCS, 2004-2007, conducted mainly in rural areas) and 2,173 from Tehran
Lipid and Glucose Study (TLGS, 2004-2006) who did not have T2DM and other chronic
diseases at baseline. Diet was assessed using validated food frequency
questionnaires. Multivariable logistic regression models were used to estimate
adjusted odds ratios (ORs) for incident T2DM.
RESULTS: We documented 902 new cases of T2DM in GCS and 81 in TLGS.
Age-standardized cumulative incidence of T2DM was 9.9% in Golestan and 8.0% in
Tehran. Daily white rice intake was significantly higher among residents of
Tehran compared to Golestan (median daily intake: 250 vs. 120 grams;
P-value < 0.001). After adjustment for potential confounders, there was no
significant association between daily white rice intake and incident T2DM in GCS.
In TLGS, the adjusted OR (95% confidence interval (CI)) was 2.1 (1.1, 3.9)
comparing participants with daily white rice intake of >250 grams/day to those
with <250.
CONCLUSIONS: We observed an increased lieklihood of T2DM associated with high
white rice intake among residents of Tehran and no association in Golestan. Our
findings, if further supported by other studies, have important public health
implications especially for countries where white rice is a major staple and
diabetes is increasing rapidly incidence is high. Further research is needed to
investigate lack of an association between lower levels of white rice intake and
T2DM.
DOI: 10.1186/s12889-016-3999-4
PMCID: PMC5282785
275. Pan Afr Med J. 2017 Aug 3;27:246. doi: 10.11604/pamj.2017.27.246.11647.
eCollection 2017.
The WHO global reference list of 100 core health indicators: the example of
Sierra Leone.
Kaiser R(1), Johnson N(1), Jalloh MF(2), Dafae F(3), Redd JT(2), Hersey S(1),
Jambai A(3).
Author information:
(1)Centers for Disease Control and Prevention (CDC) Country Office, Freetown,
Sierra Leone.
(2)Division of Global Health Protection, Center for Global Health, Centers for
Disease Control and Prevention, Atlanta, USA.
(3)Ministry of Health and Sanitation, Freetown, Sierra Leone.
The global reference list of 100 core health indicators is a standard set of
indicators published by the World Health Organization in 2015. We reviewed core
health indicators in the public domain and in-country for Sierra Leone, the
African continent and globally. Review objectives included assessing available
sources, accessibility and feasibility of obtaining data and informing efforts to
monitor program progress. Our search strategy was guided by feasibility
considerations targeting mainly national household surveys in Sierra Leone and
topic-specific and health statistics reports published annually by WHO. We also
included national, regional and worldwide health indicator estimates published
with open access in the literature and compared them with cumulative annual
indicators from the weekly national epidemiological bulletin distributed by the
Sierra Leone Ministry of Health and Sanitation. We obtained 70 indicators for
Sierra Leone from Internet sources and 2 (maternal mortality and malaria
incidence) from the national bulletin. Of the 70 indicators, 14 (20%) were
modified versions of WHO indicators and provided uncertainty intervals. Maternal
mortality showed considerable differences between 2 international sources for
2015 and the most recent national bulletin. We were able to obtain the majority
of core indicators for Sierra Leone. Some indicators were similar but not
identical, uncertainty intervals were limited and estimates differed for the same
year between sources. Current efforts to improve health and mortality
surveillance in Sierra Leone will improve availability and quality of reporting
in the future. A centralized core indicator reporting website should be
considered.
DOI: 10.11604/pamj.2017.27.246.11647
PMCID: PMC5622828
276. Lancet Diabetes Endocrinol. 2018 Jun;6(6):e6-e15. doi:
10.1016/S2213-8587(18)30150-5.
Worldwide burden of cancer attributable to diabetes and high body-mass index: a
comparative risk assessment.
Pearson-Stuttard J(1), Zhou B(2), Kontis V(2), Bentham J(3), Gunter MJ(4), Ezzati
M(5).
Author information:
(1)School of Public Health, MRC-PHE Centre for Environment and Health, Imperial
College London, London, UK; Department of Epidemiology and Biostatistics, School
of Public Health, Imperial College London, London, UK. Electronic address:
j.pearson-stuttard@imperial.ac.uk.
of Public Health, Imperial College London, London, UK.
Imperial College London, London, UK; School of Public Health, MRC-PHE Centre for
Environment and Health, Imperial College London, London, UK; School of

Mathematics, Statistics and Actuarial Science (SMSAS), University of Kent,
Canterbury, UK.
(4)Nutrition and Metabolism Section, International Agency for Research on Cancer,
World Health Organization, Lyon, France.
of Public Health, Imperial College London, London, UK; WHO Collaborating Centre
on NCD Surveillance and Epidemiology, Imperial College London, London, UK.
Corrected and republished from
Lancet Diabetes Endocrinol. 2018 Feb;6(2):95-104.
BACKGROUND: Diabetes and high body-mass index (BMI) are associated with increased
risk of several cancers, and are increasing in prevalence in most countries. We
estimated the cancer incidence attributable to diabetes and high BMI as
individual risk factors and in combination, by country and sex.
METHODS: We estimated population attributable fractions for 12 cancers by age and
sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal
to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI
categories in 2002, assuming a 10-year lag between exposure to diabetes or high
BMI and incidence of cancer, combined with relative risks from published
estimates, to quantify contribution of diabetes and high BMI to site-specific
cancers, individually and combined as independent risk factors and in a
conservative scenario in which we assumed full overlap of risk of diabetes and
high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of
cancer cases attributable to the two risk factors. We also estimated the number
of cancer cases in 2012 that were attributable to increases in the prevalence of
diabetes and high BMI from 1980 to 2002. All analyses were done at individual
country level and grouped by region for reporting.
FINDINGS: We estimated that 5·7% of all incident cancers in 2012 were
attributable to the combined effects of diabetes and high BMI as independent risk
factors, corresponding to 804 100 new cases. 187 600 (24·5%) of 766 000 cases of
liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were
attributable to these risk factors. In the conservative scenario, about 4·5%
(629 000 new cases) of all incident cancers assessed were attributable to
diabetes and high BMI combined. Individually, high BMI (544 300 cases) was
responsible for almost twice as many cancer cases as diabetes (293 300 cases).
25·8% of diabetes-related cancers (equating to 75 600 new cases) and 31·9% of
high BMI-related cancers (174 040 new cases) were attributable to increases in
the prevalence of these risk factors from 1980 to 2002.
INTERPRETATION: A substantial number of cancer cases are attributable to diabetes
and high BMI. As the prevalence of these cancer risk factors increases, clinical
and public health efforts should focus on identifying optimal preventive and
screening measures for whole populations and individual patients.
FUNDING: NIHR and Wellcome Trust.
reserved.
DOI: 10.1016/S2213-8587(18)30150-5
PMCID: PMC5982644
PMID: 29803268
277. RETRACTED ARTICLE
Lancet Diabetes Endocrinol. 2018 Feb;6(2):95-104. doi:
10.1016/S2213-8587(17)30366-2. Epub 2017 Nov 28.
Worldwide burden of cancer attributable to diabetes and high body-mass index: a
comparative risk assessment.

Pearson-Stuttard J(1), Zhou B(2), Kontis V(2), Bentham J(3), Gunter MJ(4), Ezzati
M(5).
Author information:
of Public Health, Imperial College London, London, UK. Electronic address:
j.pearson-stuttard@imperial.ac.uk.
of Public Health, Imperial College London, London, UK.
of Public Health, Imperial College London, London, UK; School of Mathematics,
Statistics and Actuarial Science (SMSAS), University of Kent, Canterbury, UK.
(4)Nutrition and Metabolism Section, International Agency for Research on Cancer,
World Health Organization, Lyon, France.
of Public Health, Imperial College London, London, UK; WHO Collaborating Centre
on NCD Surveillance and Epidemiology, Imperial College London, London, UK.
Retraction in
Lancet Diabetes Endocrinol. 2018 Jun;6(6):437.
Comment in
Lancet Diabetes Endocrinol. 2018 Feb;6(2):82-83.
Corrected and republished in
Lancet Diabetes Endocrinol. 2018 Jun;6(6):e6-e15.

BACKGROUND: Diabetes and high body-mass index (BMI) are associated with increased
risk of several cancers, and are increasing in prevalence in most countries. We
estimated the cancer incidence attributable to diabetes and high BMI as
individual risk factors and in combination, by country and sex.
METHODS: We estimated population attributable fractions for 12 cancers by age and
sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal
to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI
categories in 2002, assuming a 10-year lag between exposure to diabetes or high
BMI and incidence of cancer, combined with relative risks from published
estimates, to quantify contribution of diabetes and high BMI to site-specific
cancers, individually and combined as independent risk factors and in a
conservative scenario in which we assumed full overlap of risk of diabetes and
high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of
cancer cases attributable to the two risk factors. We also estimated the number
of cancer cases in 2012 that were attributable to increases in the prevalence of
diabetes and high BMI from 1980 to 2002. All analyses were done at individual
country level and grouped by region for reporting.
FINDINGS: We estimated that 5·6% of all incident cancers in 2012 were
attributable to the combined effects of diabetes and high BMI as independent risk
factors, corresponding to 792 600 new cases. 187 600 (24·5%) of 766 000 cases of
liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were
attributable to these risk factors. In the conservative scenario, about 4·5%
(626 900 new cases) of all incident cancers assessed were attributable to
diabetes and high BMI combined. Individually, high BMI (544 300 cases) was
responsible for twice as many cancer cases as diabetes (280 100 cases). 26·1% of
diabetes-related cancers (equating to 77 000 new cases) and 31·9% of high
BMI-related cancers (174 040 new cases) were attributable to increases in the
prevalence of these risk factors from 1980 to 2002.
INTERPRETATION: A substantial number of cancer cases are attributable to diabetes
and high BMI. As the prevalence of these cancer risk factors increases, clinical
and public health efforts should focus on identifying optimal preventive and
screening measures for whole populations and individual patients.
FUNDING: NIHR and Wellcome Trust.
reserved.
DOI: 10.1016/S2213-8587(17)30366-2
PMCID: PMC5805864
PMID: 29195904
278. Lancet. 2017 Jan 7;389(10064):37-55. doi: 10.1016/S0140-6736(16)31919-5. Epub
2016 Nov 16.
Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479
population-based measurement studies with 19·1 million participants.
Collaborators: Zhou B, Bentham J, Di Cesare M, Bixby H, Danaei G, Cowan MJ,
Paciorek CJ, Singh G, Hajifathalian K, Bennett JE, Taddei C, Bilano V,
Carrillo-Larco RM, Djalalinia S, Khatibzadeh S, Lugero C, Peykari N, Zhang WZ, Lu
Y, Stevens GA, Riley LM, Bovet P, Elliott P, Gu D, Ikeda N, Jackson RT, Joffres
M, Kengne AP, Laatikainen T, Lam TH, Laxmaiah A, Liu J, Miranda JJ, Mondo CK,
Neuhauser HK, Sundström J, Smeeth L, Soric M, Woodward M, Ezzati M, Abarca-Gómez
L, Abdeen ZA, Rahim HA, Abu-Rmeileh NM, Acosta-Cazares B, Adams R, Aekplakorn W,
Afsana K, Aguilar-Salinas CA, Agyemang C, Ahmadvand A, Ahrens W, Al Raddadi R, Al
Woyatan R, Ali MM, Alkerwi A, Aly E, Amouyel P, Amuzu A, Andersen LB, Anderssen
SA, Ängquist L, Anjana RM, Ansong D, Aounallah-Skhiri H, Araújo J, Ariansen I,

Aris T, Arlappa N, Aryal K, Arveiler D, Assah FK, Assunção MCF, Avdicová M,
Azevedo A, Azizi F, Babu BV, Bahijri S, Balakrishna N, Bandosz P, Banegas JR,
Barbagallo CM, Barceló A, Barkat A, Barros AJD, Barros MV, Bata I, Batieha AM,
Baur LA, Beaglehole R, Romdhane HB, Benet M, Benson LS, Bernabe-Ortiz A,
Bernotiene G, Bettiol H, Bhagyalaxmi A, Bharadwaj S, Bhargava SK, Bi Y, Bikbov M,
Bjerregaard P, Bjertness E, Björkelund C, Blokstra A, Bo S, Bobak M, Boeing H,
Boggia JG, Boissonnet CP, Bongard V, Braeckman L, Brajkovich I, Branca F,
Breckenkamp J, Brenner H, Brewster LM, Bruno G, Bueno-de-Mesquita HBA, Bugge A,
Burns C, Bursztyn M, de León AC, Cacciottolo J, Cameron C, Can G, Cândido APC,
Capuano V, Cardoso VC, Carlsson AC, Carvalho MJ, Casanueva FF, Casas JP, Caserta
CA, Chamukuttan S, Chan AW, Chan Q, Chaturvedi HK, Chaturvedi N, Chen CJ, Chen F,
Chen H, Chen S, Chen Z, Cheng CY, Dekkaki IC, Chetrit A, Chiolero A, Chiou ST,
Chirita-Emandi A, Cho B, Cho Y, Chudek J, Cifkova R, Claessens F, Clays E, Concin
H, Cooper C, Cooper R, Coppinger TC, Costanzo S, Cottel D, Cowell C, Craig CL,
Crujeiras AB, Cruz JJ, D'Arrigo G, d'Orsi E, Dallongeville J, Damasceno A,
Dankner R, Dantoft TM, Dauchet L, De Backer G, De Bacquer D, de Gaetano G, De
Henauw S, De Smedt D, Deepa M, Dehghan A, Delisle H, Deschamps V, Dhana K, Di
Castelnuovo AF, Dias-da-Costa JS, Diaz A, Dickerson TT, Do HTP, Dobson AJ,
Donfrancesco C, Donoso SP, Döring A, Doua K, Drygas W, Dulskiene V, Džakula A,
Dzerve V, Dziankowska-Zaborszczyk E, Eggertsen R, Ekelund U, El Ati J, Ellert U,
Elliott P, Elosua R, Erasmus RT, Erem C, Eriksen L, de la Peña JE, Evans A, Faeh
D, Fall CH, Farzadfar F, Felix-Redondo FJ, Ferguson TS, Fernández-Bergés D,
Ferrante D, Ferrari M, Ferreccio C, Ferrieres J, Finn JD, Fischer K, Föger B, Foo
LH, Forslund AS, Forsner M, Fortmann SP, Fouad HM, Francis DK, Franco MDC, Franco
OH, Frontera G, Fuchs FD, Fuchs SC, Fujita Y, Furusawa T, Gaciong Z, Gareta D,
Garnett SP, Gaspoz JM, Gasull M, Gates L, Gavrila D, Geleijnse JM, Ghasemian A,
Ghimire A, Giampaoli S, Gianfagna F, Giovannelli J, Goldsmith RA, Gonçalves H,
Gross MG, Rivas JPG, Gottrand F, Graff-Iversen S, Grafnetter D, Grajda A, Gregor
RD, Grodzicki T, Grøntved A, Gruden G, Grujic V, Gu D, Guan OP, Gudnason V,
Guerrero R, Guessous I, Guimaraes AL, Gulliford MC, Gunnlaugsdottir J, Gunter M,
Gupta PC, Gureje O, Gurzkowska B, Gutierrez L, Gutzwiller F, Hadaegh F, Halkjær

J, Hambleton IR, Hardy R, Harikumar R, Hata J, Hayes AJ, He J, Hendriks ME,
Henriques A, Cadena LH, Herrala S, Heshmat R, Hihtaniemi IT, Ho SY, Ho SC, Hobbs
M, Hofman A, Dinc GH, Hormiga CM, Horta BL, Houti L, Howitt C, Htay TT, Htet AS,
Hu Y, Huerta JM, Husseini AS, Huybrechts I, Hwalla N, Iacoviello L, Iannone AG,
Ibrahim MM, Ikram MA, Irazola VE, Islam M, Ivkovic V, Iwasaki M, Jackson RT,
Jacobs JM, Jafar T, Jamrozik K, Janszky I, Jasienska G, Jelakovic B, Jiang CQ,
Joffres M, Johansson M, Jonas JB, Jørgensen T, Joshi P, Juolevi A, Jurak G,
Jureša V, Kaaks R, Kafatos A, Kalter-Leibovici O, Kamaruddin NA, Kasaeian A, Katz
J, Kauhanen J, Kaur P, Kavousi M, Kazakbaeva G, Keil U, Boker LK,
Keinänen-Kiukaanniemi S, Kelishadi R, Kemper HCG, Kengne AP, Kersting M, Key T,
Khader YS, Khalili D, Khang YH, Khaw KT, Kiechl S, Killewo J, Kim J, Klumbiene J,
Kolle E, Kolsteren P, Korrovits P, Koskinen S, Kouda K, Koziel S, Kristensen PL,
Krokstad S, Kromhout D, Kruger HS, Kubinova R, Kuciene R, Kuh D, Kujala UM, Kula
K, Kulaga Z, Kumar RK, Kurjata P, Kusuma YS, Kuulasmaa K, Kyobutungi C,
Laatikainen T, Lachat C, Lam TH, Landrove O, Lanska V, Lappas G, Larijani B,
Laugsand LE, Laxmaiah A, Bao KLN, Le TD, Leclercq C, Lee J, Lee J, Lehtimäki T,
Lekhraj R, León-Muñoz LM, Levitt NS, Li Y, Lilly CL, Lim WY, Lima-Costa MF, Lin
HH, Lin X, Linneberg A, Lissner L, Litwin M, Lorbeer R, Lotufo PA, Lozano JE,
Luksiene D, Lundqvist A, Lunet N, Lytsy P, Ma G, Ma J, Machado-Coelho GLL, Machi
S, Maggi S, Magliano DJ, Majer M, Makdisse M, Malekzadeh R, Malhotra R, Rao KM,
Malyutina S, Manios Y, Mann JI, Manzato E, Margozzini P, Marques-Vidal P,
Marrugat J, Martorell R, Mathiesen EB, Matijasevich A, Matsha TE, Mbanya JCN,
Posso AJMD, McFarlane SR, McGarvey ST, McLachlan S, McLean RM, McNulty BA, Khir
ASM, Mediene-Benchekor S, Medzioniene J, Meirhaeghe A, Meisinger C, Menezes AMB,
Menon GR, Meshram II, Metspalu A, Mi J, Mikkel K, Miller JC, Miquel JF,
Mišigoj-Durakovic M, Mohamed MK, Mohammad K, Mohammadifard N, Mohan V, Yusoff
MFM, Møller NC, Molnár D, Momenan A, Mondo CK, Monyeki KDK, Moreira LB, Morejon
A, Moreno LA, Morgan K, Moschonis G, Mossakowska M, Mostafa A, Mota J, Motlagh
ME, Motta J, Muiesan ML, Müller-Nurasyid M, Murphy N, Mursu J, Musil V, Nagel G,
Naidu BM, Nakamura H, Námešná J, Nang EEK, Nangia VB, Narake S, Navarrete-Muñoz
EM, Ndiaye NC, Neal WA, Nenko I, Nervi F, Nguyen ND, Nguyen QN, Nieto-Martínez
RE, Niiranen TJ, Ning G, Ninomiya T, Nishtar S, Noale M, Noboa OA, Noorbala AA,
Noorbala T, Noto D, Al Nsour M, O'Reilly D, Oh K, Olinto MTA, Oliveira IO, Omar
MA, Onat A, Ordunez P, Osmond C, Ostojic SM, Otero JA, Overvad K, Owusu-Dabo E,
Paccaud FM, Padez C, Pahomova E, Pajak A, Palli D, Palmieri L, Panda-Jonas S,
Panza F, Papandreou D, Parnell WR, Parsaeian M, Pecin I, Pednekar MS, Peer N,
Peeters PH, Peixoto SV, Pelletier C, Peltonen M, Pereira AC, Pérez RM, Peters A,
Petkeviciene J, Pham ST, Pigeot I, Pikhart H, Pilav A, Pilotto L, Pitakaka F,
Plans-Rubió P, Polakowska M, Polašek O, Porta M, Portegies ML, Pourshams A,
Pradeepa R, Prashant M, Price JF, Puiu M, Punab M, Qasrawi RF, Qorbani M, Radic
I, Radisauskas R, Rahman M, Raitakari O, Raj M, Rao SR, Ramachandran A, Ramos E,
Rampal S, Reina DAR, Rasmussen F, Redon J, Reganit PFM, Ribeiro R, Riboli E, Rigo
F, de Wit TFR, Ritti-Dias RM, Robinson SM, Robitaille C, Rodríguez-Artalejo F,
Rodriguez-Perez Del Cristo M, Rodríguez-Villamizar LA, Rojas-Martinez R,
Rosengren A, Rubinstein A, Rui O, Ruiz-Betancourt BS, Horimoto ARVR, Rutkowski M,
Sabanayagam C, Sachdev HS, Saidi O, Sakarya S, Salanave B, Salazar Martinez E,
Salmerón D, Salomaa V, Salonen JT, Salvetti M, Sánchez-Abanto J, Sans S, Santos
D, Santos IS, Dos Santos RN, Santos R, Saramies JL, Sardinha LB, Margolis GS,
Sarrafzadegan N, Saum KU, Savva SC, Scazufca M, Schargrodsky H, Schneider IJ,
Schultsz C, Schutte AE, Sen A, Senbanjo IO, Sepanlou SG, Sharma SK, Shaw JE,
Shibuya K, Shin DW, Shin Y, Siantar R, Sibai AM, Silva DAS, Simon M, Simons J,
Simons LA, Sjöström M, Skovbjerg S, Slowikowska-Hilczer J, Slusarczyk P, Smeeth
L, Smith MC, Snijder MB, So HK, Sobngwi E, Söderberg S, Solfrizzi V, Sonestedt E,
Song Y, Sørensen TI, Jérome CS, Soumare A, Staessen JA, Starc G, Stathopoulou MG,
Stavreski B, Steene-Johannessen J, Stehle P, Stein AD, Stergiou GS, Stessman J,
Stieber J, Stöckl D, Stocks T, Stokwiszewski J, Stronks K, Strufaldi MW, Sun CA,
Sundström J, Sung YT, Suriyawongpaisal P, Sy RG, Tai ES, Tammesoo ML, Tamosiunas
A, Tang L, Tang X, Tanser F, Tao Y, Tarawneh MR, Tarqui-Mamani CB, Taylor A,
Theobald H, Thijs L, Thuesen BH, Tjonneland A, Tolonen HK, Tolstrup JS, Topbas M,
Topór-Madry R, Tormo MJ, Torrent M, Traissac P, Trichopoulos D, Trichopoulou A,
Trinh OTH, Trivedi A, Tshepo L, Tulloch-Reid MK, Tuomainen TP, Tuomilehto J,
Turley ML, Tynelius P, Tzourio C, Ueda P, Ugel E, Ulmer H, Uusitalo HMT, Valdivia
G, Valvi D, van der Schouw YT, Van Herck K, van Rossem L, van Valkengoed IG,
Vanderschueren D, Vanuzzo D, Vatten L, Vega T, Velasquez-Melendez G, Veronesi G,
Verschuren WMM, Verstraeten R, Victora CG, Viet L, Viikari-Juntura E, Vineis P,
Vioque J, Virtanen JK, Visvikis-Siest S, Viswanathan B, Vollenweider P,
Voutilainen S, Vrdoljak A, Vrijheid M, Wade AN, Wagner A, Walton J, Mohamud WNW,
Wang MD, Wang Q, Wang YX, Wannamethee SG, Wareham N, Wederkopp N, Weerasekera D,
Whincup PH, Widhalm K, Widyahening IS, Wiecek A, Wijga AH, Wilks RJ, Willeit J,
Willeit P, Williams EA, Wilsgaard T, Wojtyniak B, Wong TY, Wong-McClure RA, Woo
J, Woodward M, Wu AG, Wu FC, Wu SL, Xu H, Yan W, Yang X, Ye X, Yiallouros PK,
Yoshihara A, Younger-Coleman NO, Yusoff AF, Yusoff MFM, Zambon S, Zdrojewski T,
Zeng Y, Zhao D, Zhao W, Zheng Y, Zhu D, Zimmermann E, Zuñiga Cisneros J.
Comment in
Lancet. 2017 Jan 7;389(10064):3-4.
Comment on
Lancet. 2011 Feb 12;377(9765):568-77.
Lancet. 2005 Jan 15-21;365(9455):217-23.
Circulation. 2016 Aug 9;134(6):441-50.
J Hypertens. 2006 Mar;24(3):413-22.
BACKGROUND: Raised blood pressure is an important risk factor for cardiovascular
diseases and chronic kidney disease. We estimated worldwide trends in mean
systolic and mean diastolic blood pressure, and the prevalence of, and number of
people with, raised blood pressure, defined as systolic blood pressure of 140 mm
Hg or higher or diastolic blood pressure of 90 mm Hg or higher.
METHODS: For this analysis, we pooled national, subnational, or community
population-based studies that had measured blood pressure in adults aged 18 years
and older. We used a Bayesian hierarchical model to estimate trends from 1975 to
2015 in mean systolic and mean diastolic blood pressure, and the prevalence of
raised blood pressure for 200 countries. We calculated the contributions of

changes in prevalence versus population growth and ageing to the increase in the
number of adults with raised blood pressure.
FINDINGS: We pooled 1479 studies that had measured the blood pressures of 19·1
million adults. Global age-standardised mean systolic blood pressure in 2015 was
127·0 mm Hg (95% credible interval 125·7-128·3) in men and 122·3 mm Hg
(121·0-123·6) in women; age-standardised mean diastolic blood pressure was 78·7
mm Hg (77·9-79·5) for men and 76·7 mm Hg (75·9-77·6) for women. Global
age-standardised prevalence of raised blood pressure was 24·1% (21·4-27·1) in men
and 20·1% (17·8-22·5) in women in 2015. Mean systolic and mean diastolic blood
pressure decreased substantially from 1975 to 2015 in high-income western and
Asia Pacific countries, moving these countries from having some of the highest
worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also
decreased in women in central and eastern Europe, Latin America and the
Caribbean, and, more recently, central Asia, Middle East, and north Africa, but
the estimated trends in these super-regions had larger uncertainty than in
high-income super-regions. By contrast, mean blood pressure might have increased
in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015,
central and eastern Europe, sub-Saharan Africa, and south Asia had the highest
blood pressure levels. Prevalence of raised blood pressure decreased in
high-income and some middle-income countries; it remained unchanged elsewhere.
The number of adults with raised blood pressure increased from 594 million in
1975 to 1·13 billion in 2015, with the increase largely in low-income and
middle-income countries. The global increase in the number of adults with raised
blood pressure is a net effect of increase due to population growth and ageing,
and decrease due to declining age-specific prevalence.
INTERPRETATION: During the past four decades, the highest worldwide blood
pressure levels have shifted from high-income countries to low-income countries
in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure
has been persistently high in central and eastern Europe.
FUNDING: Wellcome Trust.

article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.
DOI: 10.1016/S0140-6736(16)31919-5
PMCID: PMC5220163
279. Lancet. 2017 Dec 16;390(10113):2627-2642. doi: 10.1016/S0140-6736(17)32129-3.
Epub 2017 Oct 10.
Worldwide trends in body-mass index, underweight, overweight, and obesity from
1975 to 2016: a pooled analysis of 2416 population-based measurement studies in
128·9 million children, adolescents, and adults.
Collaborators: Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM,
Acosta-Cazares B, Acuin C, Adams RJ, Aekplakorn W, Afsana K, Aguilar-Salinas CA,
Agyemang C, Ahmadvand A, Ahrens W, Ajlouni K, Akhtaeva N, Al-Hazzaa HM, Al-Othman
AR, Al-Raddadi R, Al Buhairan F, Al Dhukair S, Ali MM, Ali O, Alkerwi A,
Alvarez-Pedrerol M, Aly E, Amarapurkar DN, Amouyel P, Amuzu A, Andersen LB,
Anderssen SA, Andrade DS, Ängquist LH, Anjana RM, Aounallah-Skhiri H, Araújo J,
Ariansen I, Aris T, Arlappa N, Arveiler D, Aryal KK, Aspelund T, Assah FK,
Assunção MCF, Aung MS, Avdicová M, Azevedo A, Azizi F, Babu BV, Bahijri S, Baker
JL, Balakrishna N, Bamoshmoosh M, Banach M, Bandosz P, Banegas JR, Barbagallo CM,
Barceló A, Barkat A, Barros AJ, Barros MV, Bata I, Batieha AM, Batista RL,
Batyrbek A, Baur LA, Beaglehole R, Romdhane HB, Benedics J, Benet M, Bennett JE,
Bernabe-Ortiz A, Bernotiene G, Bettiol H, Bhagyalaxmi A, Bharadwaj S, Bhargava
SK, Bhatti Z, Bhutta ZA, Bi H, Bi Y, Biehl A, Bikbov M, Bista B, Bjelica DJ,
Bjerregaard P, Bjertness E, Bjertness MB, Björkelund C, Blokstra A, Bo S, Bobak

M, Boddy LM, Boehm BO, Boeing H, Boggia JG, Boissonnet CP, Bonaccio M, Bongard V,
Bovet P, Braeckevelt L, Braeckman L, Bragt MC, Brajkovich I, Branca F,
Breckenkamp J, Breda J, Brenner H, Brewster LM, Brian GR, Brinduse L, Bruno G,
Bueno-de-Mesquita HBA, Bugge A, Buoncristiano M, Burazeri G, Burns C, de León AC,
Cacciottolo J, Cai H, Cama T, Cameron C, Camolas J, Can G, Cândido APC, Capanzana
M, Capuano V, Cardoso VC, Carlsson AC, Carvalho MJ, Casanueva FF, Casas JP,
Caserta CA, Chamukuttan S, Chan AW, Chan Q, Chaturvedi HK, Chaturvedi N, Chen CJ,
Chen F, Chen H, Chen S, Chen Z, Cheng CY, Chetrit A, Chikova-Iscener E, Chiolero
A, Chiou ST, Chirita-Emandi A, Chirlaque MD, Cho B, Cho Y, Christensen K,
Christofaro DG, Chudek J, Cifkova R, Cinteza E, Claessens F, Clays E, Concin H,
Confortin SC, Cooper C, Cooper R, Coppinger TC, Costanzo S, Cottel D, Cowell C,
Craig CL, Crujeiras AB, Cucu A, D'Arrigo G, d'Orsi E, Dallongeville J, Damasceno
A, Damsgaard CT, Danaei G, Dankner R, Dantoft TM, Dastgiri S, Dauchet L, Davletov
K, De Backer G, De Bacquer D, De Curtis A, de Gaetano G, De Henauw S, de Oliveira
PD, De Ridder K, De Smedt D, Deepa M, Deev AD, Dehghan A, Delisle H, Delpeuch F,
Deschamps V, Dhana K, Di Castelnuovo AF, Dias-da-Costa JS, Diaz A, Dika Z,
Djalalinia S, Do HT, Dobson AJ, Donati MB, Donfrancesco C, Donoso SP, Döring A,
Dorobantu M, Dorosty AR, Doua K, Drygas W, Duan JL, Duante C, Duleva V, Dulskiene
V, Dzerve V, Dziankowska-Zaborszczyk E, Egbagbe EE, Eggertsen R, Eiben G, Ekelund
U, El Ati J, Elliott P, Engle-Stone R, Erasmus RT, Erem C, Eriksen L, Eriksson
JG, la Peña JE, Evans A, Faeh D, Fall CH, Sant'Angelo VF, Farzadfar F,
Felix-Redondo FJ, Ferguson TS, Fernandes RA, Fernández-Bergés D, Ferrante D,
Ferrari M, Ferreccio C, Ferrieres J, Finn JD, Fischer K, Flores EM, Föger B, Foo
LH, Forslund AS, Forsner M, Fouad HM, Francis DK, Franco MDC, Franco OH, Frontera
G, Fuchs FD, Fuchs SC, Fujita Y, Furusawa T, Gaciong Z, Gafencu M, Galeone D,
Galvano F, Garcia-de-la-Hera M, Gareta D, Garnett SP, Gaspoz JM, Gasull M, Gates
L, Geiger H, Geleijnse JM, Ghasemian A, Giampaoli S, Gianfagna F, Gill TK,
Giovannelli J, Giwercman A, Godos J, Gogen S, Goldsmith RA, Goltzman D, Gonçalves
H, González-Leon M, González-Rivas JP, Gonzalez-Gross M, Gottrand F, Graça AP,
Graff-Iversen S, Grafnetter D, Grajda A, Grammatikopoulou MG, Gregor RD,
Grodzicki T, Grøntved A, Grosso G, Gruden G, Grujic V, Gu D, Gualdi-Russo E,

Guallar-Castillón P, Guan OP, Gudmundsson EF, Gudnason V, Guerrero R, Guessous I,
Guimaraes AL, Gulliford MC, Gunnlaugsdottir J, Gunter M, Guo X, Guo Y, Gupta PC,
Gupta R, Gureje O, Gurzkowska B, Gutierrez L, Gutzwiller F, Hadaegh F,
Hadjigeorgiou CA, Si-Ramlee K, Halkjær J, Hambleton IR, Hardy R, Kumar RH,
Hassapidou M, Hata J, Hayes AJ, He J, Heidinger-Felso R, Heinen M, Hendriks ME,
Henriques A, Cadena LH, Herrala S, Herrera VM, Herter-Aeberli I, Heshmat R,
Hihtaniemi IT, Ho SY, Ho SC, Hobbs M, Hofman A, Hopman WM, Horimoto AR, Hormiga
CM, Horta BL, Houti L, Howitt C, Htay TT, Htet AS, Htike MMT, Hu Y, Huerta JM,
Petrescu CH, Huisman M, Husseini A, Huu CN, Huybrechts I, Hwalla N, Hyska J,
Iacoviello L, Iannone AG, Ibarluzea JM, Ibrahim MM, Ikeda N, Ikram MA, Irazola
VE, Islam M, Ismail AA, Ivkovic V, Iwasaki M, Jackson RT, Jacobs JM, Jaddou H,
Jafar T, Jamil KM, Jamrozik K, Janszky I, Jarani J, Jasienska G, Jelakovic A,
Jelakovic B, Jennings G, Jeong SL, Jiang CQ, Jiménez-Acosta SM, Joffres M,
Johansson M, Jonas JB, Jørgensen T, Joshi P, Jovic DP, Józwiak J, Juolevi A,
Jurak G, Jureša V, Kaaks R, Kafatos A, Kajantie EO, Kalter-Leibovici O,
Kamaruddin NA, Kapantais E, Karki KB, Kasaeian A, Katz J, Kauhanen J, Kaur P,
Kavousi M, Kazakbaeva G, Keil U, Boker LK, Keinänen-Kiukaanniemi S, Kelishadi R,
Kelleher C, Kemper HC, Kengne AP, Kerimkulova A, Kersting M, Key T, Khader YS,
Khalili D, Khang YH, Khateeb M, Khaw KT, Khouw IM, Kiechl-Kohlendorfer U, Kiechl
S, Killewo J, Kim J, Kim YY, Klimont J, Klumbiene J, Knoflach M, Koirala B, Kolle
E, Kolsteren P, Korrovits P, Kos J, Koskinen S, Kouda K, Kovacs VA, Kowlessur S,
Koziel S, Kratzer W, Kriemler S, Kristensen PL, Krokstad S, Kromhout D, Kruger
HS, Kubinova R, Kuciene R, Kuh D, Kujala UM, Kulaga Z, Kumar RK, Kunešová M,
Kurjata P, Kusuma YS, Kuulasmaa K, Kyobutungi C, La QN, Laamiri FZ, Laatikainen
T, Lachat C, Laid Y, Lam TH, Landrove O, Lanska V, Lappas G, Larijani B, Laugsand
LE, Lauria L, Laxmaiah A, Bao KLN, Le TD, Lebanan MAO, Leclercq C, Lee J, Lee J,
Lehtimäki T, León-Muñoz LM, Levitt NS, Li Y, Lilly CL, Lim WY, Lima-Costa MF, Lin
HH, Lin X, Lind L, Linneberg A, Lissner L, Litwin M, Liu J, Loit HM, Lopes L,
Lorbeer R, Lotufo PA, Lozano JE, Luksiene D, Lundqvist A, Lunet N, Lytsy P, Ma G,
Ma J, Machado-Coelho GL, Machado-Rodrigues AM, Machi S, Maggi S, Magliano DJ,
Magriplis E, Mahaletchumy A, Maire B, Majer M, Makdisse M, Malekzadeh R, Malhotra

R, Rao KM, Malyutina S, Manios Y, Mann JI, Manzato E, Margozzini P, Markaki A,
Markey O, Marques LP, Marques-Vidal P, Marrugat J, Martin-Prevel Y, Martin R,
Martorell R, Martos E, Marventano S, Masoodi SR, Mathiesen EB, Matijasevich A,
Matsha TE, Mazur A, Mbanya JCN, McFarlane SR, McGarvey ST, McKee M, McLachlan S,
McLean RM, McLean SB, McNulty BA, Yusof SM, Mediene-Benchekor S, Medzioniene J,
Meirhaeghe A, Meisfjord J, Meisinger C, Menezes AMB, Menon GR, Mensink GB,
Meshram II, Metspalu A, Meyer HE, Mi J, Michaelsen KF, Michels N, Mikkel K,
Miller JC, Minderico CS, Miquel JF, Miranda JJ, Mirkopoulou D, Mirrakhimov E,
Mišigoj-Durakovic M, Mistretta A, Mocanu V, Modesti PA, Mohamed MK, Mohammad K,
Mohammadifard N, Mohan V, Mohanna S, Yusoff MFM, Molbo D, Møllehave LT, Møller
NC, Molnár D, Momenan A, Mondo CK, Monterrubio EA, Monyeki KDK, Moon JS, Moreira
LB, Morejon A, Moreno LA, Morgan K, Mortensen EL, Moschonis G, Mossakowska M,
Mostafa A, Mota J, Mota-Pinto A, Motlagh ME, Motta J, Mu TT, Muc M, Muiesan ML,
Müller-Nurasyid M, Murphy N, Mursu J, Murtagh EM, Musil V, Nabipour I, Nagel G,
Naidu BM, Nakamura H, Námešná J, Nang EEK, Nangia VB, Nankap M, Narake S, Nardone
P, Navarrete-Muñoz EM, Neal WA, Nenko I, Neovius M, Nervi F, Nguyen CT, Nguyen
ND, Nguyen QN, Nieto-Martínez RE, Ning G, Ninomiya T, Nishtar S, Noale M, Noboa
OA, Norat T, Norie S, Noto D, Nsour MA, O'Reilly D, Obreja G, Oda E, Oehlers G,
Oh K, Ohara K, Olafsson Ö, Olinto MTA, Oliveira IO, Oltarzewski M, Omar MA, Onat
A, Ong SK, Ono LM, Ordunez P, Ornelas R, Ortiz AP, Osler M, Osmond C, Ostojic SM,
Ostovar A, Otero JA, Overvad K, Owusu-Dabo E, Paccaud FM, Padez C, Pahomova E,
Pajak A, Palli D, Palloni A, Palmieri L, Pan WH, Panda-Jonas S, Pandey A, Panza
F, Papandreou D, Park SW, Parnell WR, Parsaeian M, Pascanu IM, Patel ND, Pecin I,
Pednekar MS, Peer N, Peeters PH, Peixoto SV, Peltonen M, Pereira AC,
Perez-Farinos N, Pérez CM, Peters A, Petkeviciene J, Petrauskiene A, Peykari N,
Pham ST, Pierannunzio D, Pigeot I, Pikhart H, Pilav A, Pilotto L, Pistelli F,
Pitakaka F, Piwonska A, Plans-Rubió P, Poh BK, Pohlabeln H, Pop RM, Popovic SR,
Porta M, Portegies ML, Posch G, Poulimeneas D, Pouraram H, Pourshams A, Poustchi
H, Pradeepa R, Prashant M, Price JF, Puder JJ, Pudule I, Puiu M, Punab M, Qasrawi
RF, Qorbani M, Bao TQ, Radic I, Radisauskas R, Rahman M, Rahman M, Raitakari O,
Raj M, Rao SR, Ramachandran A, Ramke J, Ramos E, Ramos R, Rampal L, Rampal S,

Rascon-Pacheco RA, Redon J, Reganit PFM, Ribas-Barba L, Ribeiro R, Riboli E, Rigo
F, de Wit TFR, Rito A, Ritti-Dias RM, Rivera JA, Robinson SM, Robitaille C,
Rodrigues D, Rodríguez-Artalejo F, Del Cristo Rodriguez-Perez M,
Rodríguez-Villamizar LA, Rojas-Martinez R, Rojroongwasinkul N, Romaguera D,
Ronkainen K, Rosengren A, Rouse I, Roy JG, Rubinstein A, Rühli FJ,
Ruiz-Betancourt BS, Russo P, Rutkowski M, Sabanayagam C, Sachdev HS, Saidi O,
Salanave B, Martinez ES, Salmerón D, Salomaa V, Salonen JT, Salvetti M,
Sánchez-Abanto J, Sandjaja, Sans S, Marina LS, Santos DA, Santos IS, Santos O,
Dos Santos RN, Santos R, Saramies JL, Sardinha LB, Sarrafzadegan N, Saum KU,
Savva S, Savy M, Scazufca M, Rosario AS, Schargrodsky H, Schienkiewitz A, Schipf
S, Schmidt CO, Schmidt IM, Schultsz C, Schutte AE, Sein AA, Sen A, Senbanjo IO,
Sepanlou SG, Serra-Majem L, Shalnova SA, Sharma SK, Shaw JE, Shibuya K, Shin DW,
Shin Y, Shiri R, Siani A, Siantar R, Sibai AM, Silva AM, Silva DAS, Simon M,
Simons J, Simons LA, Sjöberg A, Sjöström M, Skovbjerg S, Slowikowska-Hilczer J,
Slusarczyk P, Smeeth L, Smith MC, Snijder MB, So HK, Sobngwi E, Söderberg S,
Soekatri MY, Solfrizzi V, Sonestedt E, Song Y, Sørensen TI, Soric M, Jérome CS,
Soumare A, Spinelli A, Spiroski I, Staessen JA, Stamm H, Starc G, Stathopoulou
MG, Staub K, Stavreski B, Steene-Johannessen J, Stehle P, Stein AD, Stergiou GS,
Stessman J, Stieber J, Stöckl D, Stocks T, Stokwiszewski J, Stratton G, Stronks
K, Strufaldi MW, Suárez-Medina R, Sun CA, Sundström J, Sung YT, Sunyer J,
Suriyawongpaisal P, Swinburn BA, Sy RG, Szponar L, Tai ES, Tammesoo ML,
Tamosiunas A, Tan EJ, Tang X, Tanser F, Tao Y, Tarawneh MR, Tarp J, Tarqui-Mamani
CB, Tautu OF, Braunerová RT, Taylor A, Tchibindat F, Theobald H, Theodoridis X,
Thijs L, Thuesen BH, Tjonneland A, Tolonen HK, Tolstrup JS, Topbas M, Topór-Madry
R, Tormo MJ, Tornaritis MJ, Torrent M, Toselli S, Traissac P, Trichopoulos D,
Trichopoulou A, Trinh OT, Trivedi A, Tshepo L, Tsigga M, Tsugane S, Tulloch-Reid
MK, Tullu F, Tuomainen TP, Tuomilehto J, Turley ML, Tynelius P, Tzotzas T,
Tzourio C, Ueda P, Ugel EE, Ukoli FA, Ulmer H, Unal B, Uusitalo HM, Valdivia G,
Vale S, Valvi D, van der Schouw YT, Van Herck K, Van Minh H, van Rossem L, Van
Schoor NM, van Valkengoed IG, Vanderschueren D, Vanuzzo D, Vatten L, Vega T,
Veidebaum T, Velasquez-Melendez G, Velika B, Veronesi G, Verschuren WM, Victora

CG, Viegi G, Viet L, Viikari-Juntura E, Vineis P, Vioque J, Virtanen JK,
Visvikis-Siest S, Viswanathan B, Vlasoff T, Vollenweider P, Völzke H, Voutilainen
S, Vrijheid M, Wade AN, Wagner A, Waldhör T, Walton J, Bebakar WMW, Mohamud WNW,
Wanderley RS Jr., Wang MD, Wang Q, Wang YX, Wang YW, Wannamethee SG, Wareham N,
Weber A, Wedderkopp N, Weerasekera D, Whincup PH, Widhalm K, Widyahening IS,
Wiecek A, Wijga AH, Wilks RJ, Willeit J, Willeit P, Wilsgaard T, Wojtyniak B,
Wong-McClure RA, Wong JY, Wong JE, Wong TY, Woo J, Woodward M, Wu FC, Wu J, Wu S,
Xu H, Xu L, Yamborisut U, Yan W, Yang X, Yardim N, Ye X, Yiallouros PK, Yngve A,
Yoshihara A, You QS, Younger-Coleman NO, Yusoff F, Yusoff MFM, Zaccagni L,
Zafiropulos V, Zainuddin AA, Zambon S, Zampelas A, Zamrazilová H, Zdrojewski T,
Zeng Y, Zhao D, Zhao W, Zheng W, Zheng Y, Zholdin B, Zhou M, Zhu D, Zhussupov B,
Zimmermann E, Cisneros JZ, Bentham J, Di Cesare M, Bilano V, Bixby H, Zhou B,
Stevens GA, Riley LM, Taddei C, Hajifathalian K, Lu Y, Savin S, Cowan MJ,
Paciorek CJ, Chirita-Emandi A, Hayes AJ, Katz J, Kelishadi R, Kengne AP, Khang
YH, Laxmaiah A, Li Y, Ma J, Miranda JJ, Mostafa A, Neovius M, Padez C, Rampal L,
Zhu A, Bennett JE, Danaei G, Bhutta ZA, Ezzati M.
Comment in
Lancet. 2018 May 5;391(10132):1773-1774.
BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are
associated with adverse health consequences throughout the life-course. Our aim
was to estimate worldwide trends in mean body-mass index (BMI) and a
comprehensive set of BMI categories that cover underweight to obesity in children
and adolescents, and to compare trends with those of adults.
METHODS: We pooled 2416 population-based studies with measurements of height and
weight on 128·9 million participants aged 5 years and older, including 31·5
million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends
from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the
following categories for children and adolescents aged 5-19 years: more than 2 SD
below the median of the WHO growth reference for children and adolescents
(referred to as moderate and severe underweight hereafter), 2 SD to more than 1
SD below the median (mild underweight), 1 SD below the median to 1 SD above the
median (healthy weight), more than 1 SD to 2 SD above the median (overweight but
not obese), and more than 2 SD above the median (obesity).
FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016
ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval
-0·42 to 0·39, posterior probability [PP] of the observed decrease being a true
decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade
(0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per
decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was
from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49,
PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06,
PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently
flattened in northwestern Europe and the high-income English-speaking and
Asia-Pacific regions for both sexes, southwestern Europe for boys, and central
and Andean Latin America for girls. By contrast, the rise in BMI has accelerated
in east and south Asia for both sexes, and southeast Asia for boys. Global
age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to
5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8%
(6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight
decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and
from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence
of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6)
among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than
30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands,
Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about
20% or more in several countries in Polynesia and Micronesia, the Middle East and
north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and
117 (70-178) million boys worldwide were moderately or severely underweight. In
the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide
were obese.
INTERPRETATION: The rising trends in children's and adolescents' BMI have
plateaued in many high-income countries, albeit at high levels, but have
accelerated in parts of Asia, with trends no longer correlated with those of
adults.
FUNDING: Wellcome Trust, AstraZeneca Young Health Programme.
reserved.
DOI: 10.1016/S0140-6736(17)32129-3
PMCID: PMC5735219
280. In Vivo. 2017 Jan 2;31(1):55-60.
Wound Healing Delay in the ZDSD Rat.
Suckow MA(1), Gobbett TA(2), Peterson RG(2).
Author information:
(1)Department of Veterinary Population Medicine, University of Minnesota, St.
Paul, MN, U.S.A. msuckowd@umn.edu.
(2)PreClinOmics, Inc., Indianapolis, IN, U.S.A.
Animal models of diabetic delayed wound healing are essential to the development
of strategies to improve clinical approaches for human patients. The Zucker
diabetic Sprague Dawley (ZDSD) rat has proved to be an accurate model of
diet-induced obesity and diabetes and we evaluated the utility of the ZDSD rat as
a model for delayed wound healing associated with diabetes and obesity. Groups of
ZDSD and Sprague Dawley (SD) rats were placed on a diabetogenic diet and
evaluated two weeks later for hyperglycemia, as a sign of diabetes. Rats with
blood glucose levels of >300 mg/dl were considered diabetic and those with blood
glucose of <180 mg/dl were considered non-diabetic. All SD rats were
non-diabetic. A full-thickness excisional skin wound was created in anesthetized
rats using a punch biopsy and wound diameter measured on days 1, 4, 7, 9 and 11.
Blood glucose levels and body weights were measured periodically before and after
wounding. Diabetic ZDSD rats had significantly greater blood glucose levels than
non-diabetic ZDSD and SD rats within 10 days of being placed on the diabetogenic
diet. Furthermore, diabetic ZDSD rats initially weighed more than non-diabetic
ZDSD and SD rats, however, by the end of the study there was no significant
difference in body weight between the ZDSD groups. By day nine, wounds in ZDSD
rats were significantly larger than those in SD rats and this persisted until the
end of the study at day fourteen. Wounds from all groups were characterized
histologically by abundant fibroblast cells, collagen deposition and macrophages.
These results demonstrate delayed wound healing in both diabetic and non-diabetic
ZDSD rats and suggest that obesity or metabolic syndrome are important factors in
wound healing delay.
Copyright© 2017, International Institute of Anticancer Research (Dr. George J.
Delinasios), All rights reserved.
DOI: 10.21873/invivo.11025
PMCID: PMC5354148
281. JMIR Res Protoc. 2017 Mar 14;6(3):e42. doi: 10.2196/resprot.7151.
Writing for Health: Rationale and Protocol for a Randomized Controlled Trial of
Internet-Based Benefit-Finding Writing for Adults With Type 1 or Type 2 Diabetes.

Crawford J(1)(2), Wilhelm K(1)(2)(3), Robins L(1)(3), Proudfoot J(2)(4).
Author information:
(1)Faces in the Street, Urban Mental Health Research Institute, St. Vincent's
Health Australia, Sydney, Australia.
(2)School of Psychiatry, Faculty of Medicine, University of New South Wales,
Sydney, Australia.
(3)Consultation Liaison Psychiatry, St. Vincent's Health Australia, Sydney,
Australia.
(4)Black Dog Institute, Sydney, Australia.
BACKGROUND: Diabetes mellitus is Australia's fastest growing chronic disease, and
has high comorbidity with depression. Both subthreshold depression and diabetes
distress are common amongst people with type 1 or type 2 diabetes, and are
associated with poorer diabetes self-care. A need exists for low-intensity
self-help interventions for large numbers of people with diabetes and diabetes
distress or subthreshold depression, as part of a stepped-care approach to
meeting the psychological needs of people with diabetes. Benefit-finding writing
is a very brief intervention that involves writing about any positive thoughts
and feelings about a stressful experience, such as an illness. Benefit-finding
writing has been associated with increases in positive affect and positive
growth, and has demonstrated promising results in trials amongst other clinical
populations. However, benefit-finding writing has not yet been examined in people
with diabetes.
OBJECTIVE: The aim of this randomized controlled trial (RCT) is to evaluate the
efficacy of an Internet-based benefit-finding writing (iBFW) intervention for
adults with type 1 or type 2 diabetes (compared to a control writing condition)
for reducing diabetes distress and increasing benefit-finding in diabetes, and
also improving a range of secondary outcomes.
METHODS: A two-arm RCT will be conducted, using the online program Writing for
Health. Adults with type 1 or type 2 diabetes living in Australia will be
recruited using diabetes-related publications and websites, and through
advertisements in diabetes services and general practitioners' offices. Potential
participants will be referred to the study-specific website for participant
information and screening. All data will be collected online. Participants will
be randomized to either iBFW about diabetes, or a control writing condition of
writing about use-of-time. Both conditions involve three daily sessions (once per
day for three consecutive days) of 15-minute online writing exercises. Outcome
measures will be administered online at baseline, one-month, and three-month
follow-ups.
RESULTS: This trial is currently underway. The primary outcomes will be diabetes
distress and benefit-finding in diabetes. Secondary outcomes will be depression,
anxiety, diabetes self-care, perceived health, and health care utilization. We
aim to recruit 104 participants. All stages of the study will be conducted online
using the Writing for Health program. Group differences will be analyzed on an
intention-to-treat basis using mixed models repeated measures. Linguistic
analyses of the writing exercise scripts, and examinations of the immediate
emotional responses to the writing exercises, will also be undertaken.
CONCLUSIONS: This RCT will be the first study to examine iBFW for adults with
type 1 or type 2 diabetes. If iBFW is found to be efficacious in reducing
diabetes distress and improving diabetes self-care and other outcomes, iBFW may
offer the potential to be a low-cost, easily accessible self-help intervention to
improve the wellbeing of adults with diabetes.
TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry
(ACTRN12615000241538).
©Joanna Crawford, Kay Wilhelm, Lisa Robins, Judy Proudfoot. Originally published
in JMIR Research Protocols (http://www.researchprotocols.org), 14.03.2017.
DOI: 10.2196/resprot.7151
PMCID: PMC5373675
PMID: 28292741

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1. PLoS One. 2018 May 16;13(5):e0195543. doi: 10.1371/journal.pone.0195543.

12-year trends in cardiovascular risk factors (2002-2005 through 2011-2014) in

patients with cardiovascular diseases: Tehran lipid and glucose study.

(1)Prevention of Metabolic Disorders Research Center, Research Institute for

Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

(2)Department of Epidemiology and Biostatistics, School of Public Health, Tehran

University of Medical Sciences, Tehran, Iran.

(3)Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid

Beheshti University of Medical Sciences, Tehran, Iran.

BACKGROUND: To examine the trend of cardiovascular diseases (CVD) risk factors

study), 2002-2005, 2005-2008, 2008-2011, and 2011-2014. Trends of CVD risk

factors were estimated using generalized estimation equation (GEE) models, by

adjusting for gender, age and propensity scores.

blood pressure, decreased from 134.88 to 129.86 mmHg, the prevalence of

low high density lipoprotein cholesterol (HDL-C), hypertriglyceridemia and high

increasing trends were observed in the consumption of anti-hypertensive, lipid

51.65%, p value = 0.054) increased during follow up.

implementation of multicomponent interventions to control CVD risk factors among

PMID: 29768511 [Indexed for MEDLINE]

2. J Endocr Soc. 2017 Jun 5;1(7):965-979. doi: 10.1210/js.2016-1073. eCollection

17β-Estradiol Promotes Islet Cell Proliferation in a Partial Pancreatectomy Mouse

Wu T(1)(2), Xu J(1)(2), Xu S(2), Wu L(2), Zhu Y(2), Li G(1)(2), Ren Z(1)(2)(3).

(1)Department of Neurobiology, School of Basic Medicine, Anhui Medical

University, Hefei, Anhui 230032, China.

Hefei, Anhui 230032, China.

(3)Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing

17β-Estradiol (E2) is a multifunctional steroid hormone in modulating metabolism

E2 plus estrogen antagonist (E2 plus ICI) groups. In the E2 group,

5-bromo-2'-deoxyuridine- and Ki67-positive cells significantly increased after

messenger RNA expression of cyclin A2 and cyclin B2 increased in E2 treatment

estrogen antagonist ICI182,780. The results indicated that E2 significantly

expression of cell cycle genes. In conclusion, E2 treatment is beneficial for

islet cell proliferation in adult mice after PPx. A partial pancreatectomy in

3. Cardiovasc Diabetol. 2018 Jun 26;17(1):93. doi: 10.1186/s12933-018-0734-8.

Abdominal subcutaneous adipose tissue: a favorable adipose depot for diabetes?

Wang H(6), Chen S(1)(2)(3)(4), Wu J(1)(2)(3)(4), Bao Y(1)(2)(3)(4), Jia

(1)Department of Endocrinology and Metabolism, Shanghai Jiao Tong University

(2)Shanghai Diabetes Institute, Shanghai, China.

(3)Shanghai Clinical Center for Diabetes, Shanghai, China.

(4)Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.

(5)Pennington Biomedical Research Center, Baton Rouge, LA, USA.

(6)Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth

People's Hospital, Shanghai, China.

(7)Department of Endocrinology and Metabolism, Shanghai Jiao Tong University

(8)Shanghai Diabetes Institute, Shanghai, China. wpjia@sjtu.edu.cn.

(9)Shanghai Clinical Center for Diabetes, Shanghai, China. wpjia@sjtu.edu.cn.

(10)Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.

BACKGROUND: Previous studies have documented that visceral adipose tissue is

positively associated with the risk of diabetes. However, the association of

subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to

newly diagnosed diabetes in Chinese adults.

resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose

(1.45-1.67) in women, respectively. However, the association between SFA and

the receiver operating characteristic curve of newly diagnosed diabetes predicted

women) were significantly larger than by the other adiposity indicators.

4. Eye (Lond). 2017 May;31(S1):S1-S20. doi: 10.1038/eye.2017.53.

Action on diabetic macular oedema: achieving optimal patient management in

treating visual impairment due to diabetic eye disease.

Silvestri G(1)(7), Freeman M(1)(8), Maisey A(1)(9), Napier J(1)(10).

(1)The Action on DMO group, UK.

(3)Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.

(4)University Hospital, Llandough, Cardiff, UK.

(5)Bradford Teaching Hospitals, Bradford, UK.

(6)The Royal Wolverhampton NHS Trust, Wolverhampton, UK.