Medicine II 6.5a LECTURER: Dr.

Panelo
DIABETES MELLITUS Part 1 DATE: February 6, 2015

OUTLINE DIABETES: WORLD AT A GLANCE

I. Standards of Medical Care in Diabetes
II. Classification and Diagnosis of Diabetes
III. Initial Evaluation and Diabetes Management Planning
IV. Foundations of Care
V. Prevention/Delay of Type 2 Diabetes
VI. Glycemic Targets
VII. Approaches to Glycemic Treatment
VIII. Cardiovascular Disease and Risk Management

REFERENCES
1. Lecture PPT
2. Recording
STANDARDS OF MEDICAL CARE IN DIABETES – 2015
 “Standards of Medical Care in Diabetes—2015” comprises all of
the current and key clinical practice recommendations of the
American Diabetes Association (ADA)
 These Standards of Care are revised annually by the
ADA’s multidisciplinary Professional Practice Committee (PPC)
o For the current revision, PPC members systematically searched
Medline for human studies related to each subsection and
published since 1 January 2014
o Recommendations were revised based on new evidence or, in
some cases, to clarify the prior recommendations or match the
strength of the word to the strength of the evident
 Standards of Care were reviewed and approved by the Executive
Committee of ADA’s Board of Directors, which includes health care
professionals, scientists, and lay people
 ADA funds development of the Standards of Care and all ADA
position statements out of its general revenues and does not use
industry support for these purposes
Fig. 3 Diabetes in the world (20-79 years) by year 2035
 Diabetes is an epidemic
 International Diabetes Federation’s (IDF) most recent estimates
indicate that 8.3% of adults – 382 million people – have diabetes, and
the number of people with the disease is set to rise beyond 592
million in less than 25 years.
 With 179 million of cases currently undiagnosed, a vast amount of
people with diabetes are progressing towards complications
unawares
 With 80% of the total number affected living in low- and middle-
income countries, the IDF Diabetes Atlas’ latest figures provide a
worrying indication of the future impact of diabetes as a major threat
to global development.
 Type 2 DM accounts for 85% to 95% of all diabetes in high-income
countries and may account for an even higher percentage in low- and
middle income countries.
 Type 2 diabetes is a common condition and a serious global health
problem. In most countries diabetes has increased alongside rapid
cultural and social changes: ageing populations, increasing
urbanisation, dietary changes, reduced physical activity and
unhealthy behavior.

Fig 1. Developing countries will bear the burden of the diabetes epidemic.
Percentage increase from the present day to 2025 in the number of people
expected to have diabetes, by region.
 Increasing rates of obesity and sedentary lifestyles against a
background of increasing lifespan will continue to push up the
prevalence of Type 2 diabetes in North America.
 However, developing countries in the Middle-East, Asia, Central and
South America, and Africa will bear the brunt of the global diabetes
epidemic.
Fig. 2 Diabetes on the rise
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Fig. 4 Increasing prevalence of Type 2 DM in adults according to the 8th Philippine
National Nutrition Survey
COMPLICATIONS ASSOCIATED WITH TYPE 2 DIABETES
 Serious microvascular and macrovascular complications of T2DM
have a devastating effect on quality of life and impose a heavy
burden on healthcare systems.
a. Diabetic retinopathy: present in 21% of people at the time
T2DM is diagnosed, diabetic retinopathy is the leading cause of
new blindness among adults aged 20–74 years.
b. Diabetic nephropathy: present in 18% of people diagnosed with
diabetes; diabetes is a leading cause of end-stage renal disease.4
c. Stroke: diabetes is associated with a 2- to 4-fold increase in
cardiovascular mortality and stroke.
d. Cardiovascular disease: 75% of individuals with T2DM die from
cardiovascular causes.
e. Diabetic neuropathy: present in 12% of people at diagnosis,
diabetic neuropathy affects approximately 70% of people with
diabetes and is a leading cause of non-traumatic lower extremity
amputations.
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 MED II 6.5a
 Early detection and treatment of diabetes is essential in order to
reduce the impact of its serious complications.
TYPE 2 DIABETES
 Caused by insulin resistance and relative insulin deficiency
 Patients may or may not need insulin treatment to survive
 May remain undiagnosed for many years, as hyperglycemia develops
slowly
 Associated with strong genetic predisposition; Heterogenous

Fig. 5 Associated complications with Type 2 DM

CLASSIFICATION AND DIAGNOSIS OF DIABETES

 The classification of diabetes includes four clinical categories
a. Type 1 diabetes - due to â-cell destruction, usually leading to
absolute insulin deficiency Fig. 7 Insulin resistance – a reduced response of target tissues to circulating insulin
b. Type 2 diabetes - due to a progressive insulin secretory defect
on the background of insulin resistance  Insulin resistance at tissue level → ↓ insulin-dependent glucose
c. Other specific types of diabetes due to other causes; e.g., uptake into liver, adipose tissue and muscle → excessive glucose
genetic defects in â-cell function, genetic defects in insulin production in the liver → hyperglycemia → compensatory ↑ in
action, diseases of the exocrine pancreas (such as cystic fibrosis), insulin secretion
and drug- or chemical-induced diabetes (such as in the  In addition, excessive triglyceride breakdown in the adipose tissue
treatment of HIV/AIDS or after organ transplantation) leads to increased circulating free fatty acids, which not only
d. Gestational diabetes mellitus (GDM) - diabetes diagnosed compete for glucose during metabolism, but also prove to be toxic to
during pregnancy that is not clearly overt diabetes the pancreas.
 Some patients cannot be clearly classified as having type 1 or type 2
diabetes
o Clinical presentation and disease progression vary considerably
in both types of diabetes
o Occasionally, patients who otherwise have type 2 diabetes may
present with ketoacidosis
o Children with type 1 diabetes typically present with the hallmark
symptoms of polyuria/polydipsia and occasionally with diabetic
ketoacidosis (DKA)
o However, difficulties in diagnosis may occur in children,
adolescents, and adults, with the true diagnosis becoming more
obvious over time

TYPE 1 DIABETES
Fig. 8 The UKPD demonstrated loss of glycemic control with time

Fig. 6 Hypothetical stages in the development of Type 1 Diabetes (from genetic

susceptibility to beta cell destruction)

 Occurs in individuals in whom genetic susceptibility outweighs

genetic protection Fig. 9 Natural History of Type 2 Diabetes
 Most likely initiated by environmental factors (usually a viral
 There is a temporal relationship between insulin resistance, insulin
infection) which triggers a host of immunologic response destroying
secretion and the development of diabetes.
the beta cells over a period of time and resulting in a progressive
o In the early stages, as insulin resistance rises, there is a
decline in beta cell function and presumably in mass leading to over
compensatory increase in insulin secretion and the individual
diabetes
remains normoglycemic.

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 MED II 6.5a
o In the long term, as the β-cells begin to fail, insulin secretion Random Plasma Glucose
falls, hyperglycemia becomes apparent and frank type 2  RPG ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms
diabetes develops. of hyperglycemia or hyperglycemic crisis
CRITERIA FOR THE DIAGNOSIS OF DIABETES  Unless there is a clear clinical diagnosis, it is preferable the same test
be repeated for confirmation, due to a greater likelihood of
 A1C > 6.5% OR
concurrence
 Fasting plasma glucose (FPG) > 126mg/dl (7.0 mmol/L) OR
o Ex: if A1C is 7.0% and repeat result is 6.8%, diabetes is confirmed
 2-hour plasma glucose > 200 mg/dl (11.1 mmol/L) during an OGTT OR o If two different tests (such as A1C and FPG) are both above the
 Random plasma glucose > 200 mg/dl (11.1 mmol/L) in patients with diagnostic threshold, this also confirms the diagnosis of diabetes
classic symptoms of hyperglycemia or hyperglycemic crisis  If with discordant results on two different tests, then the test result
above the diagnostic cut point should be repeated; the diagnosis is
Glycosilated Hemoglobin (HbA1c or A1C)
made on the basis of the confirmed test
 A1C > 6.5%
o Ex.: if a patient meets the diabetes criterion of the A1C (two
 In the absence of unequivocal hyperglycemia, result should be
results ≥6.5%) but not the FPG (<126 mg/dL or 7.0 mmol/L), or
confirmed by repeat testing.
vice versa, that person should be considered to have diabetes
 Should be performed in a laboratory using a method certified by the  Since there is preanalytic and analytic variability of all the tests, it is
National Glycohemoglobin Standardization Program (NGSP) and possible an abnormal result, when repeated, will produce a value
standardized or traceable to the Diabetes Control and Complications below the diagnostic cut point
Trial (DCCT) reference assay o This is least likely for A1C, somewhat more likely for FPG and
 Only recently added by an International Expert Committee as a third most likely for the 2-h PG
option to diagnose diabetes  In those whose test results are near the margins of the diagnostic
 Advantages over FPG and OGTT include: threshold, considering laboratory error, close monitoring is
o Greater convenience (fasting not required) warranted, with repetition of the test in 3-6 months
o Possibly greater preanalytical stability
CATEGORIES OF INCREASED RISK FOR DIABETES (PREDIABETES)
o Less day-to-day perturbations during periods of stress and
illness  In 1997 and 2003, the Expert Committee on the Diagnosis and
Classification of Diabetes Mellitus recognized a group of individuals
 Disadvantages include:
whose glucose levels did not meet the criteria for diabetes, but were
o Greater cost too high to be considered normal
o Limited availability of A1C testing in certain regions of the  “Prediabetes” is the term used for individuals with impaired fasting
developing world glucose (IFG) and/or impaired glucose tolerance (IGT), indicating the
o Incomplete correlation between A1C and average glucose in relatively high risk for the future development of diabetes
certain individuals o IFG: fasting plasma glucose (FPG) levels of 100–125 mg/dL (5.6–
 A1C levels may vary with patients’ race/ethnicity 6.9 mmol/L)
 Interpreting A1C levels in the presence of certain anemias and o IGT: 2-hour plasma glucose (2-h PG) in the 75-g oral glucose
hemoglobinopathies is particularly problematic tolerance test (OGTT) of 140–199 mg/dL (7.8–11.0 mmol/L)
o A1C 5.7-6.4%
Fasting Plasma Glucose (FPG)
 For all three tests, risk is continuous, extending below the lower
 FPG ≥126mg.dL (7.0 mmol/L)
limit of a range and becoming disproportionately greater at higher
 Fasting is defined as no caloric intake for at least 8 hours ends of the range.
 In the absence of unequivocal hyperglycemia, result should be  IFG and IGT should not be viewed as clinical entities in their own right
confirmed by repeat testing. but rather risk factors for diabetes as well as cardiovascular disease
 In addition to the A1C test, the FPG and 2-h PG may also be used to (CVD)
diagnose diabetes  IFG and IGT are associated with obesity (especially abdominal or
o Concordance between the FPG and 2-h PG tests is <100% visceral obesity), dyslipidemia with high triglycerides and/or low HDL
o The concordance between A1C and either glucose-based test is cholesterol, and hypertension
also imperfect  The World Health Organization (WHO) and a number of other
 National Health and Nutrition Examination Survey (NHANES) data diabetes organizations define the cutoff for IFG at 110 mg/dL (6.1
indicate that the A1C cut point of ≥6.5% identifies 1/3 fewer cases of mmol/L)
undiagnosed diabetes than a fasting glucose cut point of ≥126 mg/dL
(7.0 mmol/L) – FPG > A1C TESTING FOR DIABETES IN ASYMPTOMATIC PATIENTS
 Numerous studies have confirmed that, at these cut points, the 2-h  Consider testing overweight/obese adults (BMI ≥25 kg/m2 or ≥ 23
OGTT value diagnoses more screened people with diabetes kg/m2 in Asian Americans) with one or more additional risk factors
 Physical inactivity  HDL cholesterol level <35
 Of note, the lower sensitivity of A1C at the designated cut point may
 First-degree relative w/ mg/dL (0.90 mmol/L) and/or a
be offset by the test’s ability to facilitate the diagnosis diabetes triglyceride level >250 mg/dL
 High-risk race/ethnicity (e.g., (2.82 mmol/L)
2-hour Plasma Glucose (2-h PG) African American, Latino,  Women with polycystic ovarian
 2-h PG ≥ 200 mg/dL (11.1mmol/L) during an OGTT Native American, Asian syndrome (PCOS)
 The test should be performed as described by the WHO, using a American, Pacific Islander)  A1C ≥5.7%, IGT, or IFG on
glucose load containing the equivalent of 75 g anhydrous glucose  Women who delivered a baby previous testing
dissolved in water weighing >9 lb or were  Other clinical conditions
diagnosed with GDM associated with insulin
 In the absence of unequivocal hyperglycemia, result should be  Hypertension (≥140/90 mmHg resistance (e.g., severe obesity,
confirmed by repeat testing. or on therapy for acanthosis nigricans)
hypertension)  History of CVD

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 MED II 6.5a
o In addition to the listed risk factors, certain medications, such as
glucocorticoids and antipsychotics, are known to increase the
risk of T2DM
o There is compelling evidence that lower BMI cut-off points
suggest diabetes risk in some racial and ethnic groups
 In a large multiethnic cohort study, for an equivalent
incidence rate of diabetes conferred by a BMI of 30
kg/m2 in non-Hispanic whites, the BMI cutoff value was
24 kg/m2 in South Asians, 25 kg/m2 in Chinese persons,
and 26 kg/m2 in African Americans
 For all patients, particularly those who are overweight, testing should
begin at age 45 years
o Age is a major risk factor for diabetes
 If tests are normal, repeat testing at least at 3-year intervals is
reasonable
o The appropriate interval between tests is not known
o The rationale for the 3-year interval is that false negatives will be
repeated before substantial time elapses
o It is also unlikely that an individual will develop significant
complications of diabetes within 3 years of a negative test result
 To test for diabetes/prediabetes, the A1C, FPG, or 2-h 75-g OGTT are
appropriate
o However, it should be noted that the tests do not necessarily
detect diabetes in the same individuals
 In those with prediabetes, identify and, if appropriate, treat other
CVD risk factors
SCREENING FOR TYPE 2 DIABETES IN CHILDREN
 Testing to detect type 2 diabetes and prediabetes should be
considered in children and adolescents who are overweight and who
have two or more additional risk factors for diabetes
 In the last decade, the incidence of type 2 diabetes in adolescents has
increased dramatically, especially in minority populations
 ADA acknowledges the limited data supporting A1C for diagnosing
diabetes in children and adolescents. However, aside from rare
instances, such as cystic fibrosis and hemoglobinopathies, ADA
continues to recommend A1C in this cohort
DETECTION AND DIAGNOSIS OF GESTATIONAL DM
 Screen for undiagnosed type 2 diabetes at the first prenatal visit in
those with risk factors, using standard diagnostic criteria
 Screen for GDM at 24–28 weeks’ gestation in pregnant women not
previously known to have diabetes
 Screen women with GDM for persistent diabetes at 6–12 weeks
postpartum, using OGTT, nonpregnancy diagnostic criteria
 Women with a history of GDM should have lifelong screening for the
development of diabetes or prediabetes at least every 3 years
 Women with a history of GDM found to have prediabetes should
receive lifestyle interventions or metformin to prevent diabetes
 GDM was defined as any degree of glucose intolerance with onset or
first recognition during pregnancy, whether or not the condition
persisted after pregnancy, and not excluding the possibility that
unrecognized glucose intolerance may have antedated or begun
concomitantly with the pregnancy
 This definition facilitated a uniform strategy for detection and
classification of GDM, but its limitations were recognized for many
years
 Further research is needed to establish a uniform approach to
diagnosing GDM
 As the ongoing epidemic of obesity and diabetes has led to more
T2DM in women of childbearing age, the number of pregnant women
with undiagnosed type 2 diabetes has increased
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
Screening for and Diagnosis of GDM One-Step Strategy
 Perform a 75-g OGTT, with plasma glucose measurement fasting and
at 1 and 2 h, at 24–28 weeks of gestation in women not previously
diagnosed with overt diabetes
 Perform OGTT in the morning after an overnight fast of at least 8 h
 GDM diagnosis: when any of the following plasma glucose values are
exceeded
o Fasting: 92 mg/dL (5.1 mmol/L)
o 1 h: 180 mg/dL (10.0 mmol/L)
o 2 h: 153 mg/dL (8.5 mmol/L)
 The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study,
a large-scale (approximately 25,000 pregnant women) multinational
epidemiologic study, demonstrated that risk of adverse maternal,
fetal, and neonatal outcomes continuously increased as a function
of maternal glycemia at 24–28 weeks, even within ranges previously
considered normal for pregnancy. For most complications, there was
no threshold for risk. These results have led to careful
reconsideration of the diagnostic criteria for GDM
Screening for and Diagnosis of GDM Two-Step Strategy
 Step 1: Perform 50-g Glucose Load Screening Test (GLT) (nonfasting)
with plasma glucose measurement at 1 h at 24–28 weeks of gestation
in women not previously diagnosed with overt diabetes
o If plasma glucose level measured at 1 h after load is ≥140 mg/dL
(7.8 mmol/L), proceed to step 2, 100-g OGTT (Step 2)
o The American College of Obstetricians and Gynecologists (ACOG)
recommends a lower threshold of 135 mg/dL in high-risk ethnic
minorities with higher prevalence of GDM
 Step 2: The 100-g OGTT should be performed when the patient is
fasting. The diagnosis of GDM is made if 2 or more of the following
plasma glucose levels are met or exceeded:
Carpenter/Coustan NDDG
Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L)
1h 180 md/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L)
2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L)
3h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L)
 NIH consensus panel, which includes representatives from
OB/gynecology, maternal-fetal medicine, pediatrics, diabetes
research, biostatistics and other related fields, recommended
continuation of the two-step approach of screening
 Key factors reported in the decision-making process were:
o Lack of clinical trial interventions demonstrating the benefits of
the “one-step” strategy
o Potential negative consequences of identifying a large new
group of women with GDM
CYSTIC FIBROSIS-RELATED DIABETES (CFRD) (not discussed)
 CFRD is the most common comorbidity in persons with cystic
fibrosis, occurring in about 20% of adolescents, 40–50% of adults
 Diabetes is associated with worse nutritional status, more severe
inflammatory lung disease, and greater mortality from respiratory
failure
 Insulin insufficiency r/t partial fibrotic destruction of the islet mass is
the primary defect in CF
 Genetically determined function of the remaining β-cells and insulin
resistance associated with infection and inflammation may also play a
role
 Annual screening for CFRD with OGTT should begin by age 10 years
in all patients with cystic fibrosis who do not have CFRD
 A1C as a screening test for CFRD is not recommended
 During a period of stable health, diagnosis of CFRD can be made in
patients with cystic fibrosis according to usual diagnostic criteria
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 MED II 6.5a
 In patients with cystic fibrosis and IGT without confirmed diabetes,
prandial insulin therapy should be considered to maintain weight.
 Patients with CFRD should be treated with insulin to attain
individualized glycemic goals
o Recent trials comparing insulin with oral repaglinide showed no
significant difference between the groups
o Insulin remains the most widely used therapy for CFRD
 Annual monitoring for complications of diabetes is recommended,
beginning 5 years after the diagnosis of CFRD
 Encouraging data suggest that improved screening and aggressive
insulin therapy have narrowed the gap in mortality between cystic
fibrosis patients with and without diabetes, and have eliminated the
sex difference in mortality
INITIAL EVALUATION AND DIABETES MANAGEMENT PLANNING
INITIAL EVALUATION
 A complete medical evaluation should be performed to classify the
diabetes:
o Detect presence of diabetes complications
o Review previous treatment, risk factor control in patients with
established diabetes
o Assist in formulating a management plan
o Provide a basis for continuing care
 Perform laboratory tests necessary to evaluate each patient’s medical
condition
 Screening Recommendation
o Consider screening those with type 1 diabetes for other
autoimmune diseases (thyroid, vitamin B12 deficiency, celiac) as
appropriate
Components of the Comprehensive Diabetes Evaluation
A. Medical History
 Age and characteristics of onset of diabetes (e.g., DKA,
asymptomatic laboratory finding
 Eating patterns, physical activity habits, nutritional status, and
weight history; growth and development in children and
adolescents
 Diabetes education history
 Review of previous treatment regimens and response to therapy
(A1C records)
 Current treatment of diabetes, including medications, adherence
and barriers thereto, meal plan, physical activity patterns,
readiness for behavior change
 Results of glucose monitoring, patient’s use of data
 DKA frequency, severity, cause
 Hypoglycemic episodes
B. Physical Examination
 Height, weight, BMI
 BP determination, including orthostatic measurements when
indicated
 Fundoscopic examination
 Thyroid palpation
 Skin examination (for acanthosis nigricans and insulin injection
sites)
 Comprehensive foot examination
o Inspection
o Palpation of dorsalis pedis and posterior tibial pulses
o Presence/absence of patellar and Achilles reflexes
o Determination of proprioception, vibration, and
monofilament sensation
C. Laboratory evaluation
 A1C, if results not available within past 3 months
 If not performed/available within past year
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
o Fasting lipid profile, including total, LDL, and HDL
cholesterol and triglycerides
o Liver function tests
o Test for urine albumin excretion with spot urine albumin-
to-creatinine ratio
o Serum creatinine and calculated GFR
o TSH in type 1 diabetes, dyslipidemia, or women over age 50
years
D. Referrals
 Eye care professional for annual dilated eye exam
 Family planning for women of reproductive age
 Registered dietitian for Medical Nutrition Therapy (MNT)
 Diabetes self-management education/support (DSME) tools are
provided
 Dentist for comprehensive periodontal examination
 Mental health professional, if needed
MANAGEMENT
 People with diabetes should receive medical care from a team that
may include
o Physicians, nurse practitioners, physician’s assistants, nurses,
dietitians, pharmacists, mental health professionals
o In this collaborative and integrated team approach, essential
that individuals with diabetes assume an active role in their care
 Management plan should recognize Diabetes Self-Management
Education (DSME) and on-going diabetes support
o Consideration should be given to the patient’s age, school or
work schedule and conditions, physical activity, eating patterns,
social situation and cultural factors, and presence of diabetes
complications, health priorities, and other medical conditions
ASSESSMENT OF COMMON COMORBID CONDITIONS
 Consider assessing for and addressing common comorbid conditions
that may complicate management of diabetes
 Common comorbidities:
o Depression o Cognitive impairment
o Obstructive sleep apnea o Low testosterone in men
o Fatty liver disease o Periodontal disease
o Cancer o Hearing impairment
o Fractures
 These concurrent conditions present clinical challenges related to
polypharmacy, prevalent symptoms, and complexity of care
RECOMMENDATIONS FOR FOUNDATIONS OF CARE
SELF-MANAGEMENT EDUCATION AND SUPPORT
 People with diabetes should receive DSME/Diabetes Self-
Management Support (DSMS) according to National Standards for
Diabetes Self-Management Education and Support at diagnosis and
as needed thereafter
 Effective self-management, quality of life are key outcomes of
DSME/DSMS; should be measured, monitored as part of care
 DSME/DSMS should address psychosocial issues, since emotional
well-being is associated with positive outcomes
 DSME and DSMS are the ongoing processes of facilitating the
knowledge, skill, and ability necessary for diabetes self-care
o This process incorporates the needs, goals, and life experiences
of the person with diabetes
o The overall objectives of DSME and DSMS are to support
informed decision making, self-care behaviors, problem solving,
and active collaboration with the health-care team to improve
clinical outcomes, health status, and quality of life in a cost-
effective manner
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 MED II 6.5a
 DSME/DSMS programs are appropriate venues for people with
prediabetes to receive education and support to develop and
maintain behaviors that can prevent or delay the onset of diabetes
 Because DSME/DSMS can result in cost-savings and improved
outcomes, DSME/DSMS should be adequately reimbursed by third-
party payers
MEDICAL NUTRITION THERAPY (MNT)
 Nutrition therapy is recommended for all people with type 1 and
type 2 diabetes as an effective component of the overall treatment
plan
o Nutrition therapy is an integral component of diabetes
prevention, management, and self-management education
 Individuals who have prediabetes or diabetes should receive
individualized MNT as needed to achieve treatment goals, preferably
provided by a registered dietitian familiar with the components of
diabetes MNT
 Because diabetes nutrition therapy can result in cost savings and
improved outcomes such as reduction in A1C, nutrition therapy
should be adequately reimbursed by insurance and other payers
MACRONUTRIENT DISTRIBUTION
 Intensive lifestyle programs with frequent follow-up are required to
achieve significant reductions in excess body weight and improve
clinical indicators
 Evidence suggests there is no ideal percentage of calories from
carbohydrate, protein, and fat for all people with diabetes
o A recent systematic review found that there was no ideal
macronutrient distribution and that macronutrient proportions
should be individualized
 Macronutrient distribution should be based on individualized
assessment of current eating patterns, preferences, and metabolic
goals
PHYSICAL ACTIVITY
 Exercise is an important part of the diabetes management plan;
regular exercise has been shown to improve blood glucose control,
reduce cardiovascular risk factors, contribute to weight loss, and
improve well being
 Regular exercise may prevent type 2 diabetes in high-risk individuals
 Children with diabetes/prediabetes: engage in at least 60 min/day
physical activity
 Adults with diabetes: at least 150 min/wk of moderate-intensity
aerobic activity (50–70% of maximum heart rate),over at least 3
days/wk with no more than 2 consecutive days without exercise
 Evidence supports that all individuals, including those with diabetes,
should be encouraged to reduce sedentary time, particularly by
breaking up extended amount of time (>90 min) spent sitting
 If not contraindicated, adults with type 2 diabetes should perform
resistance training at least twice weekly
SMOKING CESSATION
 Studies provide convincing evidence to support the causal link
between cigarette smoking and health risks
 In newly diagnosed type 2 diabetes smokers, it was found that
smoking cessation was associated with amelioration of metabolic
parameters and reduced blood pressure and albuminuria at 1 year
 Addition of pharmacological therapy to brief counseling is more
effective than either treatment alone
 Assessment of level of nicotine dependence, which is associated with
difficulty in quitting and relapse
 Advise all patients not to smoke or use tobacco products
 Include smoking cessation counseling and other forms of treatment
as a routine component of diabetes care
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
PSYCHOSOCIAL ASSESSMENT AND CARE
 Emotional well-being is an important part of diabetes care and self-
management
 Psychological/social problems can impair the ability of the individual’s
or family’s ability to carry out diabetes care tasks and therefore
compromise health status
 Ongoing part of medical management of diabetes
 Psychosocial screening/follow-up: attitudes, medical
management/outcomes expectations, affect/mood, quality of life,
resources, psychiatric history
 Routinely screen for psychosocial problems: depression, diabetes-
related distress, anxiety, eating disorders, cognitive impairment
IMMUNIZATION
 Safe and effective vaccines that greatly reduce the risk of serious
complications from these diseases are available
 Influenza and pneumonia are common, associated with high
mortality and morbidity in the elderly and in people with chronic
diseases
 Provide routine vaccinations for children and adults with diabetes as
for the general population
 Provide influenza vaccine annually to all patients with diabetes ≥6
months of age
 Administer pneumococcal polysaccharide vaccine 23 (PPSV23) to all
patients with diabetes ≥2 years
 Adults ≥65 years of age, if not previously vaccinated, should receive
pneumococcal conjugate vaccine (PCV13), followed by PPSV23 6-12
months after initial vaccination
 Adults ≥65 years of age, if previously vaccinated with PPSV23, should
receive a follow-up ≥12 months with PCV13
 Administer hepatitis B vaccination to unvaccinated adults with
diabetes who are aged 19–59 years
 Consider administering hepatitis B vaccination to unvaccinated
adults with diabetes who are aged ≥60 years
o HBV is highly transmissible and stable for long periods of time
on surfaces such as lancing devices and blood glucose meters,
even when no blood is visible
o Blood sufficient to transmit the virus has also been found in the
reservoirs of insulin pens, resulting in warnings against sharing
such devices between patients
PREVENTION/DELAY OF TYPE 2 DIABETES
 Individuals at high risk for developing type 2 diabetes (IFG, IGT, or
both) can significantly decrease the rate of diabetes onset with
particular interventions
 Persons with an A1C of 5.7%–6.4%, IGT, or IFG should be counseled
on lifestyle changes: 7% weight loss and moderate physical activity
of at least 150 minutes/week
 Metformin has a strong evidence base and demonstrated long-term
safety, but is less effective than lifestyle modification in the Diabetes
Prevention Program (DPP) and Diabetes Prevention Program
Outcome Study (DPPOS), but may be cost-saving over a 10-year
period
 Metformin was as effective as lifestyle modification in participants
with a BMI ≥35 kg/m2, but not significantly better than placebo in
those over age 60 years
 In the DPP, for women with a history of GDM, metformin and
intensive lifestyle modification led to an equivalent 50% reduction in
diabetes risk
 Metformin therefore may reasonably be recommended for very
high-risk individuals (e.g., history of GDM, very obese, and/or those
with more severe or progressive hyperglycemia)
Page 6 of 15
 MED II 6.5a
 For other drugs, cost, side effects, and lack of a persistent effect
require consideration
 Consider Metformin for prevention of type 2 diabetes if IGT, IFG, or
A1C 5.7–6.4%
o Especially for those with BMI >35 kg/m2, age <60 years, and
women with prior GDM
 In those with prediabetes, monitor for development of diabetes
annually
 Screen for and treat modifiable risk factors for CVD
GLYCEMIC TARGETS
Fig 10. UK Prospective Diabetes Study (UKPDS) 35 was a prospective
observational study to determine the relation between exposure to
hyperglycemia over time and the risk of macrovascular or microvascular
complications in patients with type 2 diabetes who were participants in the
UKPDS.
 3,642 white, Asian Indian and Afro-Caribbean UKPDS patients who
had HbA1c measured three months after their diabetes diagnosis and
with complete data for potential confounders were included in the
sub-analysis of relative risk. Reductions in the risk of microvascular
and macrovascular complications that might be achieved by lowering
HbA1c by 1% were estimated.
 The incidence of clinical complications was found to be significantly
associated with hyperglycemia.
 The lowest risk for complication was observed in those with HbA1c
values in the normal range (< 6.0%). A 1% decrease in HbA1c was
estimated to correspond with significant reductions in any diabetes-
related endpoint, diabetes-related death, all causes mortality,
myocardial infarction, stroke, peripheral vascular disease,
microvascular disease and cataract extraction.
 The conversion factor for blood glucose mg/dl to mmol/l = x 0.0555.
GLYCEMIC CONTROL
 Two primary techniques available for health care providers and
patients to assess effectiveness of management plan on glycemic
control
o Patient self-monitoring of blood glucose (SMBG), or insterstitial
glucose
o A1C/HbA1c
 In addition to an initial evaluation and management, diabetes care
requires an assessment of glycemic control
Glucose Monitoring
 Patients on multiple-dose insulin (MDI) or insulin pump therapy
should do SMBG to monitor for and prevent asymptomatic
hypoglycemia and hyperglycemia
o Prior to meals and snacks
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
 Mostly for Type 1 diabetes
o Occasionally postprandially,
o At bedtime
 “Make sure that the patient will not be hypoglycemic at
night. Marameng hindi na gumagising at namamatay sa
hypoglycemia”[2]
o Prior to exercise
o When suspecting low blood glucose
o After treating low blood glucose until they are normoglycemic
o Prior to critical tasks such as driving
 SMBG frequency and timing should be dictated by the patient’s
specific needs and goals
 When prescribed as part of a broader educational context, SMBG
results may be helpful to guide treatment decisions and/or patient
self-management for patients using less frequent insulin injections or
noninsulin therapies
 When prescribing SMBG, ensure that patients receive ongoing
instruction and regular evaluation of SMBG technique and SMBG
results, as well as their ability to use SMBG data to adjust therapy
 The ongoing need for and frequency of SMBG should be reevaluated
at each routine visit
 When used properly, continuous glucose monitoring (CGM) in
conjunction with intensive insulin regimens is a useful tool to lower
A1C in selected adults (aged ≥25 years) with type 1 diabetes
o A 26-week randomized trial of 322 type 1 patients showed that
adults aged ≥25 years using intensive insulin therapy and CGM
experienced a 0.5% reduction in A1C (from ~7.6–7.1%)
compared with usual intensive insulin therapy with SMBG
o Overall, meta-analyses suggests that compared with SMBG,
CGM lowers A1C by ~0.26%
 Although the evidence for A1C lowering is less strong in children,
teens, and younger adults, CGM may be helpful in these groups, with
success correlating with adherence to ongoing use of the device
 CGM may be a supplemental tool to SMBG in those with
hypoglycemia unawareness and/or frequent hypoglycemic episodes
 When given variable adherence to CGM, assess individual readiness
for continuing use of CGM prior to prescribing.
 When prescribing CGM, robust diabetes education, training, and
support are required for optimal CGM implementation and ongoing
use.
A1C
 The A1C test is subject to certain limitations:
o Conditions that affect erythrocyte turnover (e.g., hemolysis,
blood loss) and hemoglobin variants must be considered,
particularly when the A1C result does not correlate with the
patient’s clinical situation
o Does not provide a measure of glycemic variability or
hypoglycemia
 For patients prone to glycemic variability (especially type 1 diabetic
patients, or type 2 diabetic patients with severe insulin deficiency),
glycemic control is best judged by the combination of result of self-
monitoring of blood glucose (SMBG) testing and A1C
 The A1C may also confirm the accuracy of a patient’s meter (or the
patient’s reported SMBG results) and the adequacy of the SMBG
testing schedule
 In patients whose therapy has changed or who are not meeting
glycemic goals, the A1C test should be performed quarterly; this
helps determine whether a patient’s glycemic targets are being
reached and maintained
 An A1C test should be performed at least two times a year in
patients who are meeting their treatment goals and have stable
glycemic control
 When needed for timely decisions on when to change therapy, point-
of-care testing (POC) for A1C may be used
Page 7 of 15
 MED II 6.5a
o The A1C machine may not be NGSP certified. Nowadays Point of
Care Testing (POCT) may be done in the office, wherein results
are available within 5 minutes.
Table 2. Mean glucose levels for specified A1C levels.
This table contains the correlation between A1C levels and mean plasma glucose
levels based on data from the international A1C-Derived Average Glucose (ADAG)
trial using frequent SMBG and continuous glucose monitoring (CGM) in 507 adults
(83% non-Hispanic whites) with type 1, type 2, and no diabetes
 The ADA and the American Association for Clinical Chemistry have
determined that the correlation (r = 0.92) is strong enough to justify
reporting both an A1C result and an estimated average glucose (eAG)
results when a clinician orders the A1C test
 For patients in whom A1C/eAG and measured blood glucose appear
discrepant, clinicians should consider the possibilities of
hemoglobinopathy or altered red cell turnover, and the options of
more frequent and/or different timing of SMBG or use of CGM
 Other measures of chronic glycemia such as fructosamine are
available, but their linkage to average glucose and their prognostic
significance are not as clear as is the case for A1C
GLYCEMIC GOALS IN ADULTS
 Lowering A1C to < 7% has been shown to reduce microvascular
complications of diabetes, and if implemented soon after the
diagnosis of diabetes, is associated with long-term reduction in
macrovascular disease; therefore, a reasonable A1C goal for many
nonpregnant adults is <7%
 The DCCT study showed definitively that improved glycemic control
is associated with significantly decreased rates of microvascular
(retinopathy and nephropathy) and neuropathic complications
 A1C goals <6.5%: those with short duration of diabetes, long life
expectancy, and no significant CVD; if can be achieved without
significant hypoglycemia or other adverse effects
 A1C goals <8%: general goal is difficult to attain despite diabetes
self-management education (DSME), appropriate glucose monitoring,
and effective doses of multiple glucose lowering agents including
insulin
o This would include those with a history of severe hypoglycemia,
limited life expectancy, advanced microvascular or
macrovascular complications, extensive comorbid conditions,
and those with longstanding diabetes
APPROACH TO THE MANAGEMENT OF HYPERGLYCEMIA
 Characteristics/predicaments toward the left justify more stringent
efforts to lower A1C, whereas those toward the right are compatible
with less stringent efforts
 Where possible, such decisions should be made in conjunction with
the patient, reflecting his or her preferences, needs, and values
 This “scale” is not designed to be applied rigidly but to be used as a
broad construct to help guide clinical decisions
 Providers should be vigilant in preventing severe hypoglycemia in
patients with advanced disease and should not aggressively attempt
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
to achieve near-normal A1C levels in patients in whom such targets
cannot be safely and reasonably achieved
 Severe or frequent hypoglycemia is an absolute indication for the
modification of treatment regimens, including setting higher glycemic
goals.
Fig 11. This depicts the elements of decision making used to determine appropriate
efforts to achieve glycemic targets
GLYCEMIC RECOMMENDATIONS FOR NONPREGNANT ADULTS WITH
DIABETES
Table 3. Recommended glycemic goals for many non-pregnant adults
A1C <7.0%
Preprandial capillary plasma glucose 80-130 mg/dl (4.4-7.2 mmol/L)
Peak postprandial capillary plasma <180 mg/dL (< 10 mmol/L)
glucose
Postprandial glucose measurements should be made 1-2h after beginning of the
meal, generally peak levels in patients with DM
 These recommendations are based on those for A1C values, with
listed blood glucose levels that appear to correlate with achievement
of an A1C of <7%
 Elevated postchallenge 2-h OGTT glucose values have been
associated with increased cardiovascular risk independent of fasting
plasma glucose (FPG) in some epidemiological studies
 In diabetic subjects, surrogate measures of vascular pathology, such
as endothelial dysfunction, are negatively affected by postprandial
hyperglycemia
 Glycemic goals should be individualized, based on:
o Duration of diabetes
o Age/life expectancy
o Comorbid conditions
o Known CVD or advanced microvascular complications
o Hypoglycemia unawareness
o Individual patient considerations
 If A1C goals are not met despite reaching preprandial glucose goals,
postprandial glucose may be targeted
 It is clear that postprandial hyperglycemia, like preprandial
hyperglycemia, contributes to elevated A1C levels, with its relative
contribution being higher at A1C levels that are closer to 7%
 Studies have shown A1C to be the primary predictor of
complications
 For individuals who have premeal glucose values within target but
have A1C values above target, monitoring postprandial plasma
glucose (PPG) 1–2 h after the start of the meal, and treatment aimed
at reducing PPG values to <180 mg/dL may help lower A1C
Page 8 of 15
 MED II 6.5a
HYPOGLYCEMIA  Despite better microvascular outcomes, intensive insulin therapy was
 This is important as well because this can kill the patient. associated with a high rate of severe hypoglycemia (62 episodes per
Differentiate between mild hypoglycemia (sweating, tachycardic) vs. 100 patient-years of therapy)
severe (loss of consciousness).[2]
THERAPY FOR TYPE 2 DIABETES
 Hypoglycemia is the leading limiting factor in the glycemic
management of patients with Type 1 and insulin-treated T2DM  Metformin, if not contraindicated and if tolerated, is the preferred
initial pharmacological agent for type 2 diabetes
 Individuals at risk for hypoglycemia should be asked about
o Metformin has a long-standing evidence base for efficacy and
symptomatic and asymptomatic hypoglycemia at each encounter
safety, is inexpensive, and may reduce risk of cardiovascular
 Glucose (15–20 g) is the preferred treatment for the conscious
events
individual with hypoglycemia, although any form of carbohydrate
 If noninsulin monotherapy (Metformin) at maximal tolerated dose
that contains glucose may be used
does not achieve or maintain the A1C target over 3 months, add a
 After 15 min of treatment, if SMBG shows continued hypoglycemia, second oral agent, a GLP-1 receptor agonist, or insulin
repeat treatment. Once normal, the individual should consume a
o Comparative effectiveness meta-analyses3 suggest that overall,
meal or snack to prevent recurrence of hypoglycemia
each new class of noninsulin agents added to initial therapy
 Glucagon should be prescribed for all individuals at significant risk of lowers A1C around 0.9–1.1%
severe hypoglycemia, and caregivers or family members of these  In newly diagnosed type 2 diabetic patients with markedly
individuals should be instructed in its administration symptomatic and/or elevated blood glucose levels or A1C, consider
 A glucagon kit requires a prescription; care should be taken to ensure insulin therapy, with or without additional agents, from the outset
that glucagon kits are not expired. o Due to the progressive nature of type 2 diabetes, insulin therapy
 Hypoglycemia unawareness or one or more episodes of severe is eventually indicated for many patients with type 2 diabetes
hypoglycemia should trigger re-evaluation of the treatment regimen  A patient-centered approach is stressed, taking into account patient
o Insulin-treated patients with hypoglycemia unawareness or an preferences, cost and potential side effects of each class, effects on
episode of severe hypoglycemia should be advised to raise their body weight, and hypoglycemia risk
glycemic targets to strictly avoid further hypoglycemia for at  Providers should avoid using insulin as a threat or describing it as a
least several weeks, to partially reverse hypoglycemia failure or punishment.
unawareness and reduce risk of future episodes  Equipping patients with an algorithm for self-titration of insulin
 Mild hypoglycemia may be inconvenient or frightening to patients doses based on SMBG results improves glycemic control in type 2
with diabetes diabetic patients initiating insulin
 Severe hypoglycemia can cause acute harm to the person with
diabetes or others, especially if it causes falls, motor vehicle accidents,
or other injury
 Ongoing assessment of cognitive function is suggested with
increased vigilance for hypoglycemia, if low cognition and/or
declining cognition is found
 Study suggested that among older adults with type 2 diabetes, a
history of severe hypoglycemia was associated with greater risk of
dementia
 Conversely, in a substudy of the ACCORD trial, cognitive impairment
at baseline or decline in cognitive function during the trial was
significantly associated with subsequent episodes of severe
hypoglycemia

APPROACHES TO GLYCEMIC TREATMENT

PHARMACOLOGICAL THERAPY FOR TYPE 1 DIABETES
 Most people with type 1 diabetes should use insulin analogs to Fig 12. Different sites of actions of various oral antidiabetic agents.
reduce hypoglycemia risk
PLEASE REFER TO APPENDIX FOR THE SUMMARY OF THE DIFFERENT
 Most people with type 1 diabetes should be treated with multiple
CLASSES OF ANTIDIABETIC AGENTS.
dose insulin (MDI) injections (3¡V4 injections/day of basal and
prandial insulin) or continuous subcutaneous insulin infusion (CSII)
Glucose Homeostasis
o Basal bolus insulin to cover for the time when patient is not
eating, in between meals, and overnight fast
o Prandial – short acting insulin before meals
o May give just 1 basal and 1 prandial insulin before the heaviest
meal of the day; other individuals will respond to premixed
insulin, composed to two types of insulin, 1 short acting and 1
intermediate acting, owing to less injections
o If requiring aggressive management, the best is 1 basal with 3
prandial insulin injections
 Educate patients in how to match prandial insulin dose to
carbohydrate intake, premeal blood glucose, and anticipated activity
 Intensive insulin therapy (> 3 injections per day of insulin, or CSII (or
insulin pump therapy) was a key part of improved glycemia and
Fig 13. Normal glucose homeostasis
better outcomes. The study was carried out with short- and
intermediate-acting human insulins
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante Page 9 of 15
 MED II 6.5a
Fig 14. In a normal individual, the kidneys filter and reabsorb 180g of
glucose/day in the nephrons
 Normally, virtually all the glucose filtered out is reabsorbed into the
blood via the proximal tubules by an active process.
 Secondary active transport of glucose also occurs in the intestines,
ensuring efficient uptake of dietary glucose and minimal urinary loss.
 Active transport is mediated via glucose co-transporters named
SGLT1, mostly at the intestinal level, and SGLT2, a low-affinity, high-
capacity co-transporter responsible for 90% of glucose reabsorption
in the proximal tubule.
 Any glucose remaining (~10%, based on animal data) is reabsorbed by
SGLT1 in the S3 segment of the proximal tubule.
TYPE 2 DM: COUNTERPRODUCTIVE INCREASE
 If the patient is obese and needs to lose weight, avoid sulfonylureas
as these cause weight gain and hypoglycemia. Hypoglycemia would
prompt the patient to eat more, hence weight gain. [2]
 Thiazolinedione is an insulin sensitizer that is good for obese patients,
but will also result in weight gain. But weight gain in this case is
caused by water retention and rechanneled fat mass from the
abdominal area to the subcutaneous compartment. Therefore, it
may be given.[2]
 DPP4 inhibitor is weight neutral and does not cause hypoglycemia,
and is therefore good for obese patients.[2]
 SGLT 2 inhibitor is the best for obese patients, but is very expensive.
It does not increase insulin secretion so it does not cause
hypoglycaemia, and it also causes weight loss[2]
 So if funds is an issue then go for GLP1, but if the patient does not
want to use injections and she wants to lose weight, go for SGLT.[2]
Fig 15. In Type 2 DM, counterproductive increases in SGLT2 up-regulation and
glucose reabsorption may occur.
 In a study by G Schernthaner, SGLT2 and GLUT 2 protein expression
was measured and isolated from healthy and type 2 DM volunteers’
fresh urine
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
 The level of glucose transporter protein expression was determined
from densitometry relative to glyceraldehyde-3-phosphate
dehydrogenase (GAPDH)
 SGLT2 level of protein expression in HEPTECs isolated from type 2
diabetes mellitus increased up to three times compared with healthy
volunteers
 GLUT2 level of protein expression in HEPTECs isolated from type 2
diabetes mellitus increased up to 10 times compared with healthy
volunteers
 The glucose analog methyl-D-[U-14C]-glucopyranoside (AMG) was
used to measure glucose uptake by the isolated HEPTECs.
 HEPTECs isolated from type 2 diabetic patients showed up to 3-fold
increase in the glucose uptake compared with those from healthy
volunteers
Fig 16. Dapagliflozin lowers tubular renal threshold for glucose excretion. Arrows
represent reduction in renal glucose threshold after dapagliflozin treatment.
ANTIHYPERGLYCEMIC THERAPY IN TYPE 2 DM
 CHECK APPENDIX FOR ANTIHYPERGLYCEMIC THERAPY ALGORITHM
 If choosing between DPP4 inhibitor, SGLT2, and sulfonylurea, and
economy is a factor, choose sulfonylurea. [2]
 Start slow, give the smallest dose that can be given, and increase the
dose slowly.[2]
 Most common reason for hypoglycemia is forgetting to eat.[2]
 If the patients are taught properly, hypoglycemia can be avoided.[2]
 If the patient is already on metformin and DPP4 inhibitor, and her
A1C went from 8 to 8.4, a GLP1 receptor antagonist or another drug
may be added. [2]
 Ideally if the patient is obese, do not give drugs that can cause further
weight gain. If the patient is thin, give sulfonylurea or insulin. [2]
 According to the American Diabetes Association, if the A1C is >9%,
combination of Metformin + sulfonylurea, Metformin + DPP4
inhibitor, or SGLT2 or GLP1 receptor agonist may be given. [2]
 CHECK APPENDIX FOR APPROACH TO STARTING AND ADJUSTING
INSULIN IN T2DM
BARIATRIC SURGERY
 Bariatric and metabolic surgeries include either gastric banding or
procedures that involve bypassing, transposing, or resecting sections
of the small intestine
 Can be an effective weight loss treatment for severe obesity
 May be considered for adults with BMI >35kg/m2 and type 2 DM,
especially if diabetes or associated comorbidities are difficult to
control with lifestyle and pharmacological therapy
 Patients with type 2 diabetes who have undergone bariatric surgery
need life-long lifestyle support and medical monitoring
 Insufficient evidence to recommend surgery in patients with BMI
<35kg/m2 outside of a research protocol
Page 10 of 15
 MED II 6.5a
 The long-term benefits, cost-effectiveness, and risks of bariatric
surgery in individuals with type 2 diabetes should be studied in well-
designed, controlled trials with optimal medical and lifestyle therapy
as the comparator
CARDIOVASCULAR DISEASE AND RISK MANAGEMENT
 Cardiovascular disease (CVD) is the major cause of morbidity and
mortality for individuals with diabetes, and is the largest contributor
to the direct and indirect costs of diabetes
 Common conditions coexisting with type 2 diabetes (e.g.,
hypertension and dyslipidemia), are clear risk factors for CVD, and
diabetes itself confers independent risk
 Benefits are observed when individual cardiovascular risk factors are
controlled to prevent/slow CVD in people with diabetes
 There is evidence that the measures of 10-year coronary heart
disease (CHD) risk among U.S. adults with diabetes have improved
significantly over the past decade
 20% of patients with cardiovascular diseases are diabetics, and CVD is
responsible for 75% of deaths in such patients
 19-31% of patients with coronary artery disease are known diabetics
o 31% in the National Registry of MI (NRMI)
o 20.3% in the Swedish registry
o 19% in Grace
STENO-2: EFFECT OF INTENSIVE VERUS CONVENTIONAL TREATMENT IN
CARDIOVASCULAR COMPLICATIONS
Fig 17. Effect of intensive versus conventional treatment on
cardiovascular complications
 Steno-2 is a randomized, open parallel trial at the Steno Diabetes
Center in Denmark, which aimed to compare the effect of a targeted,
intensified, multifactorial intervention with that of conventional
treatment on risk factors for CVD.
 Long-term targeted, intensive intervention involving multiple risk
factors reduces the risk of cardiovascular complications in patients
with T2DM and microalbuminuria
 Patients were randomly assigned to receive either conventional
treatment or intensive treatment, with a stepwise implementation
of behavior modification and pharmacological therapy that targeted
hyperglycemia, hypertension, dyslipidemia and microalbuminuria,
along with secondary prevention of CVD with aspirin.
 If patients in the intensive group were unable to maintain an A1C of <
6.5% by means of diet and increased physical activity alone after 3
months, an oral hypoglycemic agent was started.
 If the HbA1c > 7%, despite maximum doses of oral hypoglycemic
agents, the addition of insulin was recommended.
 Subjects receiving intensive therapy were much more likely to reach
their total cholesterol goal (< 175 mg/dl) (72% versus 22%, p < 0.001)
and systolic BP goal (< 130 mmHg) (46% versus 19%, p = 0.001).
 The difference between intensive and conventional therapy for
achieving HbA1c goal of < 6.5% was 15% versus 3%, p = 0.06.
 Intervention with intensive treatment reduced the risk of both
cardiovascular and microvascular complications by approximately
Group 20 & 21 | Serencio, Siquian, Singidas, Sinena, Sorsona, Sunga, Sunga, Sy, Tablante
50% compared with conventional treatment in patients with type 2
diabetes and microalbuminuria.
STENO-2: MULTIPLE RISK FACTOR INTERVENTION
Fig 18. Steno-2 studied the efficacy of multiple risk factor iterventioni in high-risk
subjects (T2DM and microalbuminuria)
 Results suggest that multiple risk factor intervention may also be
highly beneficial in subjects with the metabolic syndrome.
 Intensive therapy included:
o Reduced-fat diet
o Regular exercise
o Smoking cessation counselling
o ACE inhibitor or ARB regardless of blood pressure
o Vitamin supplementation and aspirin
o Stepwise antiglycemic and antihypertension medications
o Lipid-modifying therapy with a statin and/or fibrate
 Subjects receiving intensive therapy were much more likely to
routinely use ACE inhibitors or ARBs (data not shown). Note that it
was much more difficult to achieve systolic blood pressure goal than
diastolic blood pressure goal. The difference between intensive and
conventional therapy for HbA1c was only 0.6%.
HYPERTENSION/BLOOD PRESSURE CONTROL
Screening and Diagnosis
 Hypertension is a common comorbidity of diabetes that affects the
majority of patients, with prevalence depending on type of diabetes,
age, obesity, and ethnicity
 Hypertension is a major risk factor for both CVD and microvascular
complications
 In T1DM, hypertension is often the result of underlying nephropathy,
while in T2DM it usually coexists with other cardiometabolic risk
factors
 Blood pressure should be measured at every routine visit
 Patients found to have elevated blood pressure should have blood
pressure confirmed on a separate day
Goals
 People with diabetes and HTN: SBP <140mmHg, DBP <90mmHg
 Younger patients: SBP <130mmHg, DBP <80 mmHg if it can be
achieved without undue treatment burden
 Pregnant with DM and chronic HTN: 110-129/65-79 mmHg; in the
interest of long-term maternal health and minimizing impaired fetal
growth
Treatment
 Patients with BP >120/80 mmHg: lifestyle changes to reduce blood
pressure
 Patients with BP > 140/90 mmHg: lifestyle therapy and initiation and
titration of pharmacological therapy
Page 11 of 15
 MED II 6.5a
 Lifestyle therapy for elevated blood pressure consists of: Table 4. Recommendations for statin treatment in people with Diabetes
o Weight loss if overweight
o DASH-style dietary pattern (low salt, high potassium)
o Moderation of alcohol intake
o Increased physical activity
 Pharmacologic therapy should include:
o ACE inhibitor or an angiotensin II receptor blocker (ARB)
o If one class is not tolerated, the other should be substituted
 Multiple drug therapy (two or more agents at maximal doses) is
generally required to achieve blood pressure targets
 If ACE inhibitors, angiotensin II receptor blockers (ARBs), or diuretics
are used, monitor serum creatine/estimated glomerular filtration
rate (eGFR) and serum potassium levels
 ACE inhibitors and angiotensin II receptor blockers (ARBs) are
contraindicated during pregnancy
 The cause of death in T2 DM is MI and stroke. This stresses the
importance of screening for CVD (HTN), and appropriate  All ages with diabetes and overt CVD: high-intensity statin therapy
management. This is the goal. Remember this! and lifestyle therapy
DYSLIPIDEMIA/LIPID MANAGEMENT  40 years old with DM and CVD risk factors: moderate or high-
intensity statin and lifestyle therapy
 Patients with type 2 diabetes have an increased prevalence of lipid
abnormalities, contributing to their high risk of CVD  40-75 years with DM and no CVD risk factors: moderate-intensity
statin and lifestyle therapy
 Lipid profile is important: increased triglycerides, decreased HDL
 40–75 years with DM and CVD risk factors: high-intensity statin and
 In adults, a screening lipid profile is reasonable:
lifestyle therapy
o At first diagnosis
 75 years with DM and no CVD risk factors: moderate-intensity statin
o At initial medical evaluation
therapy and lifestyle therapy
o And/or at age 40 years and periodically (1-2yrs) thereafter
 75 years with DM and CVD risk factors: moderate- or high-intensity
Goals and Treatment Recommendations statin therapy and lifestyle therapy
 Recommend lifestyle modification focusing on:  Always recommend lifestyle therapy. If (+) CVD risk factors, give
o Reduction of saturated fat, trans fat, cholesterol intake high-intensity statins. If (-) CVD risk factors, give moderate-intensity
o Increase of n-3 fatty acids, viscous fiber, plant stanols/sterols statins.
o Weight loss (if indicated)
ANTIPLATELET AGENTS
o Increased physical activity
 Low-dose aspirin therapy (75–162 mg/day) as a primary prevention
 Intensity lifestyle therapy and optimize glycemic control for patients
strategy in those with type 1 or type 2 diabetes at increased
with:
cardiovascular risk (10-year risk >10%), and who are not at increased
o Triglyceride levels: <150 mg/dL (1.7 mmol/L) and/or
risk for bleeding
o HDL cholesterol: >40 mg/dL (1.0 mm/L) in men; >50 mg/dL (1.3
o Aspirin therapy is only for a specific group of patients. Before, all
mmol/L) in women
DM patients were given ASA, but it did not improve outcome. [2]
 For patients with fasting triglyceride levels > 500 mg/dL (5.7 mmol/L),
 This includes most men aged >50 years or women aged >60 years
evaluate for secondary causes and consider medical therapy to
who have at least one additional major risk factor:
reduce the risk of pancreatitis
o Family history of CVD
 Cholesterol laboratory testing may be helpful in monitoring
o Hypertension
adherence to therapy but may not be needed once the patient is
o Smoking
stable on therapy
o Dyslipidemia
 Combination therapy has been shown not to provide additional o Albuminuria
cardiovascular benefit above statin therapy alone and is not generally
 Aspirin should not be recommended for CVD prevention for adults
recommended
with diabetes at low CVD risk since the potential adverse effects
Recommendations for Statin Treatment in People with DM from bleeding offset the potential benefits
 For patients of all ages with diabetes and overt CVD, high-intensity o Low risk: 10-year CVD risk <5%, men <50 years, women <60
statin therapy should be added to lifestyle therapy. years with no major additional CVD risk factors
 In patients in these age groups with multiple other risk factors,
 Adjust intensity of statin therapy based on individual patient
clinical judgment is required
response to medication (e.g. side effects, tolerability, LDL cholesterol
levels)  Aspirin use in patients under the age of 21 years is contraindicated
due to the associated risk of Reye syndrome
 Statin therapy is contraindicated in pregnancy
 Aspirin therapy (75-162 mg/day) as a secondary prevention strategy
 Moderate intensity: Atorvastatin 10 mg and Rosuvastatin 10 mg [2]
in those with diabetes with a history of CVD
 High intensity: Atorvastatin 40 to 80 mg and Rosuvastatin >20 mg [2]  For patients with CVD and documented aspirin allergy, Clopidogrel
(75 mg/day) should be used
 Dual antiplatelet therapy is reasonable for up to a year after an
acute coronary syndrome

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 MED II 6.5a
 A P2Y12 receptor antagonist in combination with aspirin should be Ee0wWz p0whZ, s3cR3t 4dm!r3r! tH!z 1’z 4 ü! 
used for at least 1 year in patients following an acute coronary
syndrome.
o Evidence supports use of either ticagrelor or clopidogrel if no
percutaneous coronary intervention (PCI) was performed, and
the use of clopidogrel, ticagrelor, or prasugrel if PCI was
performed2

CARDIOVASCULAR DISEASE
Screening
 In asymptomatic patients, routine screening for coronary artery
disease (CAD) is not recommended, as it does not improve outcomes
as long as cardiovascular disease (CVD) risk factors are treated
 Perform CAD screening for all T2DM patients [2]
 Assess cardiovascular risk factors in all patients with DM annually:
o Dyslipidemia
o Hypertension
o Smoking
o Family history of premature coronary disease
o Albuminuria

Treatment
 To reduce risk of cardiovascular events in patients with known CVD,
consider:
o ACE inhibitor
o Aspirin
o Statin therapy
 With prior MI: β-blockers should be continued for at least 2 years
after the event
 Patients at increased CVD risk should receive aspirin and a statin, and
ACE inhibitor or ARB therapy if hypertensive, unless there are
contraindications to a particular drug class
 While clear benefit exists for ACE inhibitor and ARB therapy in
patients with nephropathy or hypertension, the benefits in patients
with CVD in the absence of these conditions are less clear, especially
when LDL cholesterol is concomitantly controlled2,3
 In patients with symptomatic heart failure, avoid thiazolidinedione
treatment
 In patients with stable CHF, metformin may be used if renal function
is normal but should be avoided in unstable or hospitalized patients
with CHF

Edited by: DJPabua

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 Medicine II 6.5a LECTURER: Dr. Panelo
DIABETES MELLITUS Part 1 - Appendix DATE: February 6, 2015

APPENDIX
Table 5. Properties of anti-hyperglycemic agents

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 MED II 6.5a

Fig 19. General recommendations for antihyperglycemic therapy in Type 2 Diabetes as outlined in the ADA-European Association for the Study of Diabetes (EASD). Definitions: DPP-
4-i,DPP-4 inhibitor; Fx’s, bone fractures; GI, gastrointestinal; GLP-1-RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea; TZD, thiazolidinedione

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