Obesity in Adults

19/6/2016 DynaMed Plus: Obesity in adults
Obesity in adults
Overview and Recommendations
Background
Obesity is most often defined as a body mass index (BMI) ≥ 30 kg/m2 and is subclassified as:
class 1 obesity is BMI 3034.9 kg/m2
class 3 obesity (also called morbid obesity) is BMI > 40 kg/m2
Risk factors for obesity include:
older age
lower socioeconomic status in developed countries
genetic predisposition
fast food intake and consumption of sugary beverages
physical inactivity
stress and other mental illnesses
disordered sleep
medications
childhood obesity
Obesity is associated with increased morbidity and mortality, including increased risk of cardiovascular events and increased risk of certain cancers.
A positive energy balance (increased energy intake and/or decreased energy expenditure in relation to each other) of 5060 calories/day sustained over a year may
lead to an increase weight of > 5.3 lbs (2.4 kg).
Evaluation
Screen all patients ≥ 18 years old for obesity and offer intensive counseling and behavioral interventions to patients with body mass index (BMI) ≥ 30 kg/m2
(Strong recommendation).
Body mass index should be measured for assessment of obesity classification but it does not directly measure adiposity and in muscular patients the implications of
elevated BMI are less clear.
In patients with a BMI < 35 kg/m2, the addition of waist circumference (measured at the iliac crest of the pelvis) should be considered for obesity risk classification
with:
low risk defined as a waist circumference < 37 inches (94 cm) for men, < 31.5 inches (80 cm) for women
high risk defined as a waist circumference ≥ 37 inches (94 cm) for men, ≥ 31.5 inches (80 cm) for women
very high risk defined as a waist circumference ≥ 40.2 inches (102 cm) for men, ≥ 34.6 inches (88 cm) for women
A waisttohip circumference ratio of > 1 in men and > 0.85 in women is associated with increased health risk.
Tests that may be useful for identifying complications of obesity or associated conditions include a fasting glucose, glucose tolerance test, or HbA1C, lipid panel,
liver enzymes, complete blood count, and thyroidstimulating hormone.
Blood pressure should also be assessed to evaluate for comorbid hypertension.
Management
Diet and exercise are the preferred methods for weight loss.
Adults can lose 12 lbs/week (0.450.91 kg/week) by consuming 5001,000 fewer kilocalories/day.
Effective diets include a portion control plate, low fat diet, Mediterranean diet, low carbohydrate diet, low glycemic index diet, and commercial weight loss
diets. However, most patients return to their baseline weight after 1224 months.
Moderateintensity exercise is recommended for adults with obesity (Strong recommendation). More than 150 minutes/week can achieve significant weight
loss.
Consider addition of medications to diet, physical activity, and behavior therapy to augment weight loss, but they may have adverse effects which often lead to
discontinuation.
Orlistat blocks intestinal fat absorption, is available without prescription, is modestly effective (2.9 kg [6.4 lbs]), but has gastrointestinal side effects including
oily spotting, flatus with discharge, fecal urgency, and fecal incontinence.
Lorcaserin (Belviq) is a serotonin receptor agonist which may promote weight loss but can have gastrointestinal side effects and can cause serotonin
syndrome if combined with other medications that have serotonergic properties including many psychiatric medications.
Phentermine is a sympathomimetic medication which is available as monotherapy or in combination with topiramate (Qsymia) but can cause or worsen
hypertension.
Metformin can promote weight loss in patients with comorbid prediabetes or diabetes mellitus. It can also promote weight loss in patients without comorbid
conditions but is not FDA approved in this cohort of patients.
Offer bariatric surgery to patients with a BMI ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with comorbidities (Strong recommendation). Compared with nonsurgical
management, bariatric surgery associated with reduced mortality, better longterm weight loss (maintained up to 10 years), higher reductions in comorbidities such
as diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea, and improved fertility in women.
Obese patients should participate in a comprehensive behavioral intervention which is highintensity (such as ≥ 14 sessions over 6 months), onsite, and delivered
by a trained professional in a group or individual setting (Strong recommendation).
A 5%15% weight loss may greatly reduce complications and improve metabolic parameters in obese or overweight persons.
Related Summaries
Obesity (list of topics)
Obesity in children and adolescents
Diets for weight loss
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Physical activity for weight loss
Weightloss medications for obesity in adults
Weightloss nonprescription medications and supplements
Bariatric surgery
General Information
Description
obesity is usually defined as body mass index (BMI) ≥ 30 kg/m2(1, 4)
BMI defined as weight in kg divided by square of height in meters, or use BMI calculator
overweight defined as BMI 2529.9 kg/m2
obesity categorized into 3 classes
class 3 obesity (also called severe obesity) is BMI > 40 kg/m2
Epidemiology
Incidence/Prevalence
worldwide prevalence of overweight or obesity 36.9% in men and 38% in women in 2013
based on systematic review of observational studies
systematic review of 543 observational studies and 1,769 health surveys and reports from 183 countries evaluating prevalence of overweight or obesity
between 1980 and 2013
agestandardized global prevalence of overweight or obesity (body mass index ≥ 25 kg/m2) in adults ≥ 20 years old in 2013
36.9% (36.3%37.4%) in men
38% (37.5%38.5%) in women
prevalence of overweight or obesity significantly higher in developed countries compared to developing countries
global prevalence of overweight or obesity significantly increased in 2013 vs. 1980
Reference Lancet 2014 Aug 30;384(9945):766, editorial can be found in Lancet 2014 Aug 30;384(9945):728
prevalence of obesity in Western countries
in United States
obesity in 35% of men and 37% of women among adults ≥ 25 years old in United States from 2007 to 2012
based on aggregate data from crosssectional study
15,208 adults ≥ 25 years old from National Health and Nutrition Examination Survey (NHANES) 20072008, 20092010, and 20112012
evaluated
prevalence of overweight in 40% of men and 30% of women
prevalence of obesity in 35% of men and 37% of women
Reference JAMA Intern Med 2015 Aug 1;175(8):1412
obesity in 36% (overweight in 34%) of adults in United States in 20112012 in crosssectional study of 5,181 adults (NHANES) (JAMA 2014 Feb
26;311(8):806 fulltext), commentary can be found in JAMA 2014 Jul;312(2):188
obesity in 52% of black adults and 38% of white adults in United States in 2005
based on crosssectional study
29,818 adults in United States had inperson assessment regarding sociodemographic information, physiciandiagnosed conditions, sleep
duration, moods, and activity limitations (2005 National Health Interview Survey)
prevalence of obesity 52% in black and 38% in white adults (odds ratio 1.80, 95% CI: 1.66–1.95, p < 0.001)
Reference Clin Pract (Lond) 2013 Sep;10(5): fulltext
obesity developed in about 30% of adults in United States with healthy body mass index at baseline over 30year period
based on longitudinal study
4,117 white adults (aged 3060 years) from Massachusetts, United States had ≥ 2 exams between 1971 and 2001 as part of the Framingham Heart
Study
among adults with healthy body mass index at baseline, about 25%35% of men and 30% of women were obese within 30 years (estimated from
figure)
Reference Ann Intern Med 2005 Oct 4;143(7):473, summary for patients can be found in Ann Intern Med 2005 Oct 4;143(7):I12
in England(1)
obesity in 24% of men and 26% of women in 2011
overweight/obesity in about 66% of adults in 2004
morbid obesity (body mass index > 40 kg/m2) in 0.9% of men and 2.6% of women in 2004
overweight or obesity in 63% of adults in Scotland in 2003 in crosssectional study of 6,574 adults (2003 Scottish Health Survey) (BMC Public Health 2010
Jun 11;10:330 fulltext)
obesity in 18.3% (overweight in 33.6%) of adults in Canada in 2011 in crosssectional study of about 12,000 adults (National Population Health Survey)
(CMAJ Open 2014 Jan;2(1):E18 fulltext)
obesity in 28.3% (overweight in 35%) of adults in Australia in 20112012 in crosssectional study of about 33,500 persons in Australia (Australian Health
Survey) (Australian Bureau of Statistics Australian Health Survey: First Results, 201112 PDF)
in countries in which obesity is not defined as body mass index ≥ 30 kg/m2
obesity in 7.1% (overweight in 17.6%) adults in China in 2002
209,849 persons (67% adult) in China were surveyed in 2002
obesity among Chinese adults defined as body mass index ≥ 28 kg/m2 (overweight as 2427.9 kg/m2)
obesity in 7.1% (overweight in 17.6%) of adults
Reference BMJ 2006 Aug 19;333(7564):362 fulltext
obesity in 10.3% of adults (≥ 15 years old) in Pakistan
8,972 adults (≥ 15 years old) in Pakistan were surveyed (National Health Survey of Pakistan)
obesity among IndoAsian adults defined as body mass index ≥ 27 kg/m2 (overweight as 2326.9 kg/m2)
obesity in 10.3% (overweight in 14.7%) of adults
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Reference CMAJ 2006 Oct 24;175(9):1071 fulltext, editorial can be found in CMAJ 2006 Oct 24;175(9):1081 fulltext
in United States, increased prevalence in African American women(2)
in the United Kingdom, increased prevalence in(1)
black Caribbean adults
black African women
Pakistani women
Obesity risk in ethnic groups
Likely risk factors
increased age(1)
in developed countries, lower socioeconomic status and education level (especially in women)(1)
positive energy balance (increased energy intake and/or decreased energy expenditure in relation to each other) may be due to(1)
modern environment
genetic predisposition
psychological factors such as stress
medication adverse effects
life stage (such as pregnancy or menopause)
life events (such as smoking cessation, marriage, or vacation)
factors associated with increased visceral/abdominal adipose tissue include
increased age
male gender
family history
Asian and Indian Asian ethnicity
dysregulation of endocannabinoid system
decreased growth hormone levels
fructose consumption
sedentary lifestyle
Reference Physiol Rev 2013 Jan;93(1):359 fulltext
Genetic predisposition
increased risk of obesity if parents are overweight or obese(1)
correlation in body mass index appears to be stronger in monozygotic than dizygotic twins, including in twins reared apart (level 2 [midlevel] evidence)
based on retrospective cohort study
673 pairs of twins (born in Sweden between 1886 and 1958) selfreported height and weight through questionnaires
46% were reared apart from each other, and 37% were monozygotic (zygosity determined through physical similarity)
sample from Swedish Twin Registry, twins reared together were chosen to be agematched to twins reared apart
body mass index correlation coefficient (1.0 would indicate a perfect positive correlation) in monozygotic vs. dizygotic twins (no p value reported)
in men reared together 0.74 vs. 0.33
in men reared apart 0.7 vs. 0.15
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in women reared together 0.66 vs. 0.27
in women reared apart 0.66 vs. 0.25
Reference N Engl J Med 1990 May 24;322(21):1483 fulltext, editorial can be found in N Engl J Med 1990 May 24;322(21):1522 fulltext and N Engl J
Med 1990 May 24;322(21):1530 fulltext, commentary can be found in N Engl J Med 1990 Oct 11;323(15):1067 fulltext
concordance rates for being overweight may be greater for monozygotic than dizygotic twins (level 2 [midlevel] evidence)
based on cohort study
4,071 male twins (United States military veterans born between 1917 and 1927, 48% monozygotic) were assessed for height and weight via physical exam at
mean age 20 years and again via questionnaire at 25year followup
concordance rates for monozygotic vs. dizygotic twins
for being ≥ 20% overweight
at first assessment, 57% vs. 27% (p < 0.005)
at 25year followup, 60% vs. 40% (p < 0.005)
for being ≥ 35% overweight
at first assessment 44% vs. 12% (p < 0.005)
at 25year followup, 43% vs. 9% (p < 0.005)
authors note that prevalence of overweight/obese at first assessment was low due to military requirements
Reference JAMA 1986 Jul 4;256(1):51
parental obesity during childhood and patient obesity at ≥ 3 years old are associated with increased risk of obesity during young adulthood (level 2 [mid
level] evidence)
854 adults' and their parents' heights and weights were assessed from medical records in Washington state, United States
all adults were born 19651971 and were aged 2129 years at time of study
adults excluded if they had a chronic condition that may affect height or weight or were born at < 36 weeks gestational age
adult obesity defined as mean body mass index in adulthood > 27.8 kg/m2 for men and 27.3 kg/m2 for women
obesity in 16% of adults
Risk of Obesity in Adulthood in Multivariate Analysis:
1 Parent Obese During 2 Parents Obese During Childhood
Childhood Age Obesity During Childhood Age*
Childhood Age** Age**
12 years No increased risk OR 3.2 (95% CI 1.85.7) OR 13.6 (95% CI 3.750.4)
35 years OR 4.7 (95% CI 2.58.8) OR 3.0 (95% CI 1.75.3) OR 15.3 (95% CI 5.741.3)
1014 years OR 22.3 (95% CI 10.547.1) OR 2.2 (95% CI 1.23.8) No increased risk
Abbreviation: OR, odds ratio.
* Odds ratio in comparison to no obesity during childhood age.
** Odds ratio in comparison to 0 parents obese during childhood age.
Reference N Engl J Med 1997 Sep 25;337(13):869 fulltext, editorial can be found in N Engl J Med 1997 Sep 25;337(13):926 fulltext
identification of alleles associated with obesity appear to have limited value in predicting obesity (level 2 [midlevel] evidence)
based on diagnostic cohort study without independent validation cohort
249,796 persons from 80 studies were assessed for associations between single nucleotide polymorphisms and obesity
geneticsusceptibility score calculated by summing the number of body mass indexrelated alleles weighted by effect size of allele
32 alleles associated with increased body mass index (p < 5 × 108) were identified by genomewide association studies
effect size determined from Atherosclerosis Risk in Communities study of 8,120 persons of European descent
predictive value assessed by area under receiver operating characteristic (ROC) curve (range 0.5 [no predictive value] to 1 [perfect predictive value])
0.574 using genetic susceptibility score only (p < 0.001 compared to area of 0.5)
0.575 using genetic susceptibility score combined with factors based on age and gender (p < 0.001 compared to area of 0.5)
0.515 using factors based on age and gender only (p = 0.023 compared to area of 0.5)
Reference Nat Genet 2010 Nov;42(11):937 fulltext, commentary can be found in Circ Cardiovasc Genet 2014 Jun;7(3):395
Dietary behavior
increased risk of obesity with high intake of caloriedense foods(1)
fast food consumption associated with increased body mass index in adults (level 2 [midlevel] evidence)
based on systematic review of mostly observational studies
review of 16 studies (3 trials, 13 observational studies) assessing effect of fast food consumption on body weight or energy intake in adults, adolescents,
and/or children
fast food consumption associated with
increased body mass index (BMI) in all 3 prospective cohort studies that included only adults (13,619 adults)
increased weight in prospective cohort analysis of 1 randomized trial with 891 adult women
conflicting evidence associating fast food consumption with BMI in 3 crosssectional studies with adults
Reference Obes Rev 2008 Nov;9(6):535
restaurant hamburger consumption associated with increased risk for obesity in African American women (level 2 [midlevel] evidence)
based on prospective cohort study
19,479 nonobese African American women aged 2139 years were assessed with questionnaire in 1995 and every 2 years for 14 years (Black Women's
Health Study [BWHS])
development of obesity during 14 year study in 36%
restaurant (including fastfood) foods associated with increased risk for obesity in adjusted analysis include
hamburgers
13 times/month (hazard ratio [HR] 1.11, 95% CI 1.041.19)
4 times/month (HR 1.14, 95% CI 1.051.24)
≥ 8 times/month (HR 1.27, 95% CI 1.141.41)
Chinese food ≥ 8 times/month (HR 1.2, 95% CI 1.051.37)
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fried chicken 4 times/month (HR 1.1, 95% CI 1.011.2) (but ≥ 8 times/month is not associated with increased risk)
dietary behaviors not associated with increased risk of obesity include intake of sugary drinks, restaurant fried fish, restaurant pizza, and restaurant Mexican
food
Reference Ethn Dis 2013 Autumn;23(4):445 fulltext
increased exposure to takeaway food outlets associated with higher obesity rates in employed adults in United Kingdom
based on crosssectional study of 5,442 working adults aged 2962 years in United Kingdom who completed food frequency questionnaire
takeaway food outlet exposure assessed at home, work, and along commuting routes
compared to lowest quartile of takeaway food outlet exposure, highest quartile associated with significantly increased rates of obesity and higher body mass
index
Reference BMJ 2014 Mar 13;348:g1464 fulltext
poor dietary behaviors and exercise beliefs are associated with greater likelihood of obesity in adults in rural western United States
1,817 adults from rural western United States were assessed with questionnaires
obesity in 25%
factors associated with increased likelihood of obesity in multivariate analysis include
decreased belief that participant gets as much exercise as needed
increased likelihood of eating while doing other activities
increased frequency of watching television
increased likelihood of ordering supersized portions of food
increased frequency of drinking sweetened beverages
decreased belief that physical activity improves participant's enjoyment (based on several questions)
Reference Int J Obes Relat Metab Disord 2003 Jun;27(6):684
eating ≥ 33% of daily energy intake at midday associated with slight decrease in likelihood of obesity in adults in United States
239 African American and nonHispanic white adults were assessed with questionnaires and clinic examination (University of California Los Angeles
Energetic Study)
true energy intake assessed via 2point doublylabeled water
overweight or obesity in 51% and moderatetovigorous exercise for ≤ 150 minutes/week in 74%
proportion energy intake in overweight/obese vs. healthyweight adults
in morning 25% vs. 23% (not significant)
at midday 35% vs. 39% (p < 0.01)
in evening 40% vs. 38% (not significant)
among 99 adults whose reported energy intake was within 25% of true energy intake
decreased likelihood of obesity if ≥ 33% of daily energy intake was at midday in adjusted analysis (odds ratio 0.34, 95% CI 0.120.95)
no association with likelihood of obesity if ≥ 33% of daily energy intake was in morning or in evening in adjusted analysis
Reference J Hum Nutr Diet 2014 Apr;27 Suppl 2:255
Lifestyle
inactive lifestyle(1)
history of being overweight (including adults who have lost weight)(1)
cessation from smoking (risk may decrease with increased physical activity)(1)
increased television watching
sitting while watching television associated with increased risk of obesity in adult women (level 2 [midlevel] evidence)
50,277 female nurses in United States aged 3055 years without obese body mass index, cardiovascular disease, cancer, or diabetes in 1992 were
assessed via questionnaire for lifestyle behavior and body composition and followedup at 6 years (part of Nurses' Health Study)
obese body mass index at followup in 7.5%
compared to 01 hours/week
sitting while watching television for > 1 hour/week associated with increased risk of obesity in adjusted multivariate analysis
25 hours/week (risk ratio [RR] 1.22, 95% CI 1.061.42)
620 hours/week (RR 1.42, 95% CI 1.241.63)
2140 hours/week (RR 1.65, 95% CI 1.411.93)
> 40 hours/week (RR 1.94, 95% CI 1.512.49)
sitting away from home (such as at work or driving) for > 40 hours/week (but not ≤ 40 hours/week) associated with increased risk of obesity (RR
1.25, 95% CI 1.021.54) in adjusted multivariate analysis
standing or walking around at home for > 20 hours/week (but not ≤ 20 hours/week) associated with reduced risk of obesity in adjusted
multivariate analysis
2140 hours/week (RR 0.78, 95% CI 0.630.97)
> 40 hours/week (RR 0.77, 95% CI 0.610.97)
standing or walking around at home for > 1 hour/week not associated with reduced risk of obesity in adjusted multivariate analysis
Reference JAMA 2003 Apr 9;289(14):1785 fulltext, commentary can be found in JAMA 2003 Jul 16;290(3):332
watching television for ≥ 3 hours/day associated with increased likelihood of obesity in young Australian adults
based on crosssectional analysis of prospective cohort study
2,439 adolescents in Brisbane, Australia were assessed with questionnaires and physical exam at ages 14 and 21 years (MaterUniversity of
Queensland Study of Pregnancy and Its Outcomes [MUSP])
obesity in 12% at age 21 followup
television watching ≥ 3 hours/day associated with increased likelihood of obesity (body mass index ≥ 30 kg/m2) at age 21 in multivariate analysis
watching television ≥ 3 hours/day at age 21 and
≥ 3 hours/day at age 14 (odds ratio [OR] 2.31, 95% CI 1.523.51)
< 3 hours/day at age 14 (OR 2.33, 95% CI 1.413.85)
watching television < 3 hours/day at age 21 and ≥ 3 hours/day at age 14 (OR 1.52, 95% CI 0.992.35)
consistent results for obesity defined by waist circumference and waisttohip ratio
Reference Public Health Nutr 2013 Jan;16(1):54
watching television ≥ 8 hours/week associated with increased likelihood of obesity in young white women in United States
6,049 women (mean age 22 years) in Unites States who were not pregnant or disabled and who selfidentified as nonHispanic white, nonHispanic
black, or Hispanic were assessed with questionnaires (Wave III of the National Longitudinal Study of Adolescent Health [Add Health])
comparing white, black, and Hispanic women
BMI 26 kg/m2 vs. 28.5 kg/m2 vs. 27.3 kg/m2 (p < 0.05 for black or Hispanic women compared to white women, not significant between black
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and Hispanic women)
hours/week watching television 11.2 vs. 14.7 vs. 10.6 (p < 0.05 for white or Hispanic women compared to back women, not significant between
white and Hispanic women)
watching television ≥ 8 hours/week associated with increased BMI in white but not black or Hispanic women in subgroup analysis
other factors associated with increased BMI in adjusted analysis
black, MexicanAmerican, or Puerto Rican ethnicity
increasing age
high school or less education level
not employed or in school
parental obesity
Reference Obesity (Silver Spring) 2010 May;18(5):1015 fulltext
watching television ≤ 840 minutes/week associated with reduced likelihood of obesity in older Japanese adults, regardless of physical activity level
1,806 adults in Japan aged 6574 years were assessed with questionnaires
20% were overweight or obese
watching television ≤ 840 minutes/week and moderatetovigorous physical activity ≥ 150 minutes/week associated with reduced likelihood of obesity
in multivariate analysis (odds ratio 0.67, 95% CI 0.470.97)
consistent results for watching television ≤ 840 minutes/week and moderatetovigorous physical activity < 150 minutes/week
no significant difference between watching television > 840 minutes/week and moderatetovigorous physical activity < vs. ≥ 150 minutes/week
Reference J Epidemiol 2012;22(1):50 fulltext, commentary can be found in J Epidemiol 2013 Sep 5;23(5):396 fulltext and J Epidemiol 2013 Sep
5;23(5):398 fulltext
obese friend, obese spouse, and obese sibling associated with increased risk of obesity in adults in social network analysis of 12,067 adults in United States
(Framingham Heart Study) (N Engl J Med 2007 Jul 26;357(4):370 fulltext)
commuting to work by public or active transportation each associated with slightly decreased body mass index compared to private transportation (level
2 [midlevel] evidence)
7,534 adults (mean age 43 years) in United Kingdom who provided health assessment data in national survey were analyzed
74% commuted to work by private transportation, 11% by public transportation, and 15% by active transportation (walking or cycling)
mean body mass index 28 kg/m2 in men and 27 kg/m2 in women
compared to private transportation, decreased body mass index with active transportation in men (adjusted mean difference 0.97 kg/m2, 95% CI 0.4 to 1.55
kg/m2)
consistent results with public transportation in men and active or public transportation in women
Reference BMJ 2014 Aug 19;349:g4887 fulltext, editorial can be found in BMJ 2014 Aug 19;349:g5020, extended commentary can be found in BMJ 2014
Sep 30;349:g5915, BMJ 2014 Sep 30;349:g5919, BMJ 2014 Sep 30;349:g5921
Stress
conflicting evidence for association between stress and increased likelihood of obesity in adults
stress associated with increased likelihood of obesity in adults in Canada
obesity in 18.1% in men and 16% in women
compared to adults who reported being "not at all" stressed, likelihood of obesity increased in adults who reported being
"extremely" stressed (adjusted odds ratio 1.23, 95% CI 1.131.35)
"quite a bit" stressed (adjusted odds ratio 1.08, 95% CI 1.021.15)
Reference Prev Med 2012 Nov;55(5):464
stress associated with increased likelihood of obesity in Australian women living in socioeconomically disadvantaged areas (level 2 [midlevel]
evidence)
1,382 women (aged 1846 years) from socioeconomically disadvantaged areas of Victoria, Australia were surveyed in 20072008 and at 3year follow
up (Resilience for Eating and Activity Despite Inequality study)
perceived stress assessed with 4item Perceived Stress Scale (PSS) (total score range in this study 4 [not stressed] to 20 [very stressed])
obesity in 20.9% at baseline and 23.6% at followup (no p value reported)
increase of 1 unit in baseline perceived stress associated in multivariate analysis with
increased likelihood at followup of obesity (odds ratio [OR] 1.11, 95% CI 11.23)
decreased likelihood at followup of leisure time physical activity
for 53 minutes to 4 hours weekly (OR 0.93, 95% CI 0.880.98)
for ≥ 5 hours weekly (OR 0.89, 95% CI 0.840.94)
no associations found between baseline perceived stress and followup measures of likelihood of being overweight, sitting time, drinking nondiet soft
drinks, or eating salty snacks, candy, cakes, pastries, or pizza
Reference BMC Public Health 2013 Sep 11;13:828 fulltext
increased stress associated with behaviors that may lead to obesity in employed adults in Seattle, Washington, United States
based on crosssectional analysis of randomized trial
621 employed adults in Seattle, Washington, United States were assessed via questionnaire (as part of Promoting Activity and Changes in Eating
[PACE] trial)
mean body mass index 29.2 kg/m2
mean perceived stress score 12.7 (assessed with 10item PSS, total score range 0 [not stressed] to 40 [very stressed])
perceived stress not associated with body mass index
increase of perceived stress by 9 points in PSS score associated in adjusted multivariate analysis with
7.1% increased likelihood of eating while doing other activities most of the time (p = 0.01)
0.44 fewer fruits or vegetables eaten/day among adults who usually eat while doing other activities most of the time (p = 0.001)
0.13 more fast food meals eaten/day among adults who usually eat while doing other activities most of the time (p = 0.001)
decreased physical activity
49.8 fewer minutes/week of walking (p = 0.02)
5.3% decreased likelihood of regularly engaging in sweatinducing exercise (p = 0.02)
authors report that stress levels were average relative to United States population and suggest that association between stress and body mass index may
be significant in sample of adults with greater stress levels
Reference Prev Chronic Dis 2012;9:E152 fulltext
financial stress and baseline obesity associated with increased likelihood of obesity 12 years later in adults in Australia (level 2 [midlevel] evidence)
7,787 adults in Australia were assessed with inperson interviews and questionnaires in 2008, 2009, and 2010 (as part of the Household Income and Labor
Dynamics in Australia [HILDA])
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obesity in 2010 in 33% of adults with and 22% of adults without financial stress in both 2008 and 2009 (no p value reported)
factors associated with increased likelihood of obesity in 2010 in multivariate analysis adjusted for covariates including obesity in 2008
obesity in 2008 (adjusted risk ratio [RR] 11.88, 95% CI 10.7613.12)
financial stress in both (compared to neither) 2008 and 2009 (adjusted RR 1.2, 95% CI 1.11.3)
university degree in 2008 associated with decreased likelihood of obesity in 2010 (adjusted RR 0.89, 95% CI 0.830.95)
Reference Obesity (Silver Spring) 2014 Feb;22(2):616
exhaustion and little satisfaction with social network associated with increased likelihood of obesity in adult women in Denmark (level 2 [midlevel]
evidence)
4,753 adults in Copenhagen, Denmark were assessed with physical examination and questionnaire in 19911994 and followup in 20012003 (part of
Copenhagen City Heart Study)
mean baseline body mass index 25 kg/m2
vital exhaustion score range 0 (no exhaustion) to 17 (high exhaustion)
baseline factors in women associated with increased likelihood of obesity at followup in adjusted multivariate analysis
2 major life events in childhood (adjusted odds ratio [OR] 2.2, 95% CI 1.323.72) (but no association with < 2 or ≥ 3 major life events)
vital exhaustion score 1017 (compared to 0) (adjusted OR 2.4, 95% CI 1.135.09) (significant association also for score 14 but not score 59)
only somewhat or no satisfaction with social network (adjusted OR 1.62, 95% CI 1.082.43)
baseline factors not associated with likelihood of obesity at followup include major adult or work life events, cohabitation, regular contact with family or
friends, economic hardship, or daily use of sleep medication
no baseline factors in men associated with obesity at followup
Reference Eur J Epidemiol 2012 Feb;27(2):119
work stress with little coworker support associated with increased likelihood of obesity (level 2 [midlevel] evidence)
10,308 adults (aged 3555 years) from civil service departments in London, United Kingdom were assessed via questionnaire in 19851988 (baseline) and 3
more times during 19year followup (Whitehall II cohort study)
reported work stress with little coworker support
at ≥ 3 of 4 assessments over 19 years associated with increased risk for obesity at 19year followup in adjusted analysis (odds ratio 1.7, 95% CI 1.07
2.71)
not associated with obesity at 19year followup among subgroup of adults who were not obese at baseline
Reference Am J Epidemiol 2007 Apr 1;165(7):828 fulltext
Sleep behavior
short sleep duration
short sleep duration associated with increased likelihood of obesity in North American and European adults (level 2 [midlevel] evidence)
based on systematic review of prospective cohort studies
review of 11 studies with 197,906 adults assessing association between selfreported sleep duration and future obesity
short sleep duration defined as ≤ 5 hours in 9 studies and ≤ 6 hours in 2 studies
long sleep duration defined as ≥ 9 hours in 5 studies, ≥ 8 hours in 3 studies, and ≥ 7 hours in 1 study
obesity defined as BMI ≥ 30 kg/m2 for European and American cohorts (5 studies) and BMI ≥ 25 kg/m2 for Japanese cohorts (5 studies) and 1
Canadian cohort (which did not distinguish between overweight and obese)
short sleep duration associated with increased risk of future obesity analysis of 9 studies
odds ratio 1.48 (95% CI 1.241.78)
consistent results for subgroups based on male gender, female gender, North American cohort, European cohort, followup > 5 years, and follow
up ≤ 5 years
association not significant for Japanese cohorts
long sleep duration not associated with likelihood of future obesity in analysis of 8 studies
Reference Sleep Med 2014 Dec;15(12):1456
sleeping ≤ 6 hours/night associated with increased likelihood of obesity in black and white adults in United States
29,818 adults in United States had inperson assessment regarding sociodemographic information, physiciandiagnosed conditions, sleep duration,
moods, and activity limitations (2005 National Health Interview Survey)
prevalence of obesity 52% in black and 38% in white adults (odds ratio [OR] 1.80, 95% CI 1.66–1.95)
likelihood of obesity in adults who slept ≤ 6 hours/night compared to adults sleeping 78 hours/night
increased for black adults (OR 1.98, 95% CI 1.692.3) in adjusted analysis
increased for white adults (OR 1.2, 95% CI 1.11.31) in adjusted analysis
likelihood of obesity in adults who slept ≥ 9 hours/night compared to adults sleeping 78 hours/night
increased for black adults (OR 1.48, 95% CI 1.141.93) in adjusted analysis
decreased for white adults (OR 0.77, 95% CI 0.670.89) in adjusted analysis
Reference Clin Pract (Lond) 2013 Sep;10(5): fulltext
sleeping < 5 hours/night or > 10 hours/night associated with increased likelihood of obesity in adults in France
24,671 adults (aged 1585 years) in France had telephone interviews from 2009 to 2010 (Institut National de Prévention et d'Education pour la Santé
[INPES] Baromètre Santé)
adults with obesity compared to normalweight adults
are more likely to sleep < 5 hours/night (adjusted odds ratio 1.2, 95% CI 1.11.4) in multivariate analysis
may be more likely to sleep > 10 hours/night (adjusted odds ratio 1.3, 95% CI 11.7) in multivariate analysis
Reference PLoS One 2014;9(9):e106950 fulltext
disruption of circadian rhythm
rotating shift work associated with increased likelihood of obesity and increased body mass index in Italian adults
339 adult employees of the Italian railway service were assessed with questionnaire and physical examination
rotating shift workers worked 2 morning shifts, 2 evening shifts, 2 night shifts, and then 3 days off
daytime workers worked 8 hours/day (starting 7:00 AM 8:00 AM) for 5 days/week
body mass index 27.6 kg/m2 for rotating shift workers and 26.7 kg/m2 for daytime workers (p < 0.05)
factors associated with increased likelihood for overweight or obesity in multivariate analysis
family history of obesity (odds ratio [OR] 9.79, 95% CI 1.2874.74)
age 3554 years (relative to < 35 years old) (OR 2.38, 95% CI 1.135)
rotating shift (OR 1.93, 95% CI 1.013.71)
factors not associated with likelihood of overweight or obesity included age ≥ 55 years (relative to < 35 years old), alcohol consumption, dietary
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behavior, or physical activity (occupational or leisuretime)
later midpoint of sleep on nonwork days relative to work days associated with increased likelihood of obesity in adults in Europe
about 65,000 persons, mostly from central Europe, took online survey
data excluded if "extreme" sleep times or biometric information, no regular weekly work schedule with weekly nonwork days, or use of alarm clocks
on nonwork days
factors associated with increased likelihood of being overweight or obese in multivariate analysis include
increased age (odds ratio [OR] 69.9, 95% CI 59.682)
later midpoint of sleep on nonwork days relative to work days (OR 3.3, 95% CI 2.54.3)
factors associated with decreased likelihood of being overweight or obese in multivariate analysis include
increased sleep duration (OR 0.008, 95% CI 0.0050.013)
earlier midpoint of sleep on nonwork days (OR 0.268, 95% CI 0.1940.371)
Reference Curr Biol 2012 May 22;22(10):939, editorial can be found in Curr Biol 2012 May 22;22(10):R405
increased light while sleeping associated with increased likelihood of obesity in women
113,343 women in the United Kingdom ≥ 16 years old were assessed with questionnaire (Breakthrough Generations Study)
light level in sleeping room classified as
lightest if light enough to read or see across the room
middle if light enough to see hand but not across the room
darkest if too dark to see your hand or if participant wears sleeping mask
compared to women who slept in lightest level, lower likelihood of obesity in adjusted multivariate analysis for women who slept in
middle level (odds ratio 0.9, 95% CI 0.870.94)
darkest level (odds ratio 0.83, 95% CI 0.790.88)
Reference Am J Epidemiol 2014 Aug 1;180(3):245, editorial can be found in Am J Epidemiol 2014 Aug 1;180(3):251
Mental disorders
serious mental health problems (due in part to side effects of medication)(1)
numerous psychiatric medications associated with increased risk of obesity(1)
learning disabilities(1)
depression associated with increased risk for developing longterm obesity (level 2 [midlevel] evidence)
based on systematic review of prospective cohort studies
review of 15 studies assessing association between depression and overweight and/or obesity
depression among patients with healthy body mass index at baseline
associated with increased risk of obesity at ≥ 5year followup in adjusted analysis of 9 studies with 6,436 patients (odds ratio 1.4, 95% CI 1.151.71)
not associated with increased or decreased risk of being overweight (body mass index ≥ 25 kg/m2and < 30 kg/m2) in analysis of 7 studies with 4,382
patients
possible publication bias
Reference Arch Gen Psychiatry 2010 Mar;67(3):220
increased risk of obesity in patients with common mental disorders
based on followup of Whitehall II study
Whitehall II study collected data on 10,308 government employees aged 3555 years at baseline in 19851988
data available from 4,363 adults at 19year followup
odds ratios for obesity at fourth screening (p for trend < 0.001)
1.33 (95% CI 11.77) for adults with common mental disorder at 1 previous screening
1.64 (95% CI 1.132.36) for adults with common mental disorder at 2 previous screenings
2.01 (95% CI 1.213.34) for adults with common mental disorder at 3 previous screenings
Reference BMJ 2009 Oct 6;339:b3765 fulltext, editorial can be found in BMJ 2009 Oct 6;339:b3868
bingeeating disorder associated with increased likelihood of class III obesity in adults with history of some mental disorder
9,282 Englishspeaking adults in United States had inperson diagnostic assessments in 20012003 (National Comorbidity Survey Replication [NCSR]
survey)
interviews based on the World Health Organization Composite International Diagnostic Interview
2,980 adults randomly selected from 5,692 adults who had a history of anxiety, mood, substance, or impulsecontrol disorders were further assessed for an
eating disorder
prevalence of bingeeating disorder was 2.8% lifetime (1.2% 12month)
increased likelihood of class III obesity (body mass index > 40 kg/m2) in adults with bingeeating disorder compared to adults without any eating disorder
(odds ratio 4.9, 95% CI 2.211)
Reference Biol Psychiatry 2007 Feb 1;61(3):348 fulltext
food addiction
food addiction in 7.7% of overweight or obese adults and 1.6% of normal weight or underweight adults
652 adults (64% women) from Newfoundland and Labrador, Canada without serious metabolic, cardiovascular or endocrine conditions were assessed
for BMI and food addiction (with Yale Food Addiction Scale)
62% were overweight or obese, and 38% were normal weight or underweight
food addiction in 7.7% of overweight or obese adults and 1.6% of normal weight or underweight adults (p < 0.05)
consistent results with body fat percentagedetermined overweight/obese status
effect greater in women
of 35 adults with food addiction, 89% were overweight or obese
food addiction is not associated with increased body mass index in mostly obese adults seeking weightloss treatment
178 adults (92% were obese) seeking weightloss treatment were assessed for BMI, food addiction (with Yale Food Addiction Scale), and depression
(with Beck Depression Inventory)
adults were excluded if diagnoses of nonfood substance abuse, serious medical conditions, bingeeating disorder, or severe depression
food addiction in 15%
comparing adults with vs. without food addiction
BMI 36 vs. 36.1 (not significant)
Beck Depression Inventory 17.1 vs. 9.2 (p < 0.001) (total score range 0 [no depression] to 63 [severe depression])
8/35
Reference Appetite 2013 Aug;67:22 fulltext
Childhood factors
childhood mental disorders and possible neurological deficits
poor childhood motor coordination associated with increased likelihood of obesity in adults (level 2 [midlevel] evidence)
7,990 persons born in 1958 in United Kingdom were assessed for motor coordination at age 7 and/or at age 11 (in 6,875 children), and for body mass
index by trained interviewer at age 33 (part of National Child Development Study)
age 7 assessment classroom teacher indicated poor ability in hand control, coordination, and overall clumsiness, scored as "certainly,"
"somewhat," "no," and "unsure"
age 11 assessment medical officer measured height and weight and administered functional assessments
factors during childhood associated with increased likelihood of obesity at age 33 in adjusted multivariate analysis
at age 7 as assessed by school teacher
"certainly" clumsy (odds ratio [OR] compared to "no" clumsiness 2.04, 95% CI 1.313.2) (consistent results for "somewhat" clumsy)
"certainly" poor hand control (OR compared to good hand control 1.48, 95% CI 1.042.1) (consistent results for "somewhat" poor hand
control)
"certainly" poor coordination (OR compared to good coordination 1.57, 95% CI 1.012.45) (not significant for "somewhat" poor
coordination)
at age 11 as assessed during medical exam, poor performances at
marking squares (OR for each increment in improvement [maximum 200] 0.82, 95% CI 0.750.89)
copying designs (OR for each increment in improvement [maximum 12] 0.88, 95% CI 0.810.97)
picking up matches (OR for each additional second it took to pick up 20 matches 1.09, 95% CI 11.18)
Reference BMJ 2008 Aug 12;337:a699 fulltext
being clumsy at age 7 associated with increased risk of obesity at age 50 (OR 1.6, 95% CI 1.182.18) in followup of 5,921 adults (PLoS One
2013;8(11):e79586 fulltext)
childhood ADHD in males associated with increased risk of obesity in adulthood
111 men with childhood attention deficit hyperactivity disorder (ADHD) and 111 men without childhood ADHD selfreported weight and height at
mean age 41 years
obesity in 41.4% with childhood ADHD vs. 21.6% without childhood ADHD (p = 0.002)
Reference Pediatrics 2013 Jun;131(6):e1731 fulltext
lower IQ at age 11 associated with obesity at age 42 in prospective cohort study of 17,414 persons in United Kingdom (Int J Obes (Lond) 2006
Sep;30(9):1422)
childhood abuse
childhood sexual and physical abuse associated with increased risk of development of severe obesity in adulthood
10,774 adolescents and young adults (aged 1222 years) without severely obese (≥ 40 kg/m2) body mass index were assessed via examination in 1996
and at 13year followup (cohort from United States National Longitudinal Study of Adolescent Health [Add Health])
childhood sexual and physical abuse associated with increased risk of development of severe obesity in adulthood
in nonminority women, hazard ratio 2.5 (95% CI 1.34.8)
in nonminority men, hazard ratio 3.6 (95% CI 1.58.5)
Reference Pediatr Obes 2014 Oct;9(5):351
child and adolescent physical and sexual abuse associated with slight increased risk of obesity in adulthood in black women
33,298 black women aged 2169 years from Black Women's Health Study completed selfadministered questionnaires regarding current physical
measurements and early life experience of physical and sexual abuse
compared to no abuse, highest severity of exposure to child and adolescent physical and sexual abuse associated with increased risk of
body mass index ≥ 30 kg/m2 (adjusted risk ratio [RR] 1.14, 95% CI 1.081.21)
waist circumference > 35 inches (88.9 cm) (adjusted RR 1.18, 95% CI 1.11.27)
Reference Pediatrics 2012 Aug;130(2):245
childhood physical abuse associated with increased BMI scores in adulthood (level 2 [midlevel] evidence)
410 children aged 011 years with history of maltreatment matched on age, sex, race/ethnicity, and social class with 303 children without history
of abuse or neglect and followed up to mean age 41 years
childhood physical abuse (but not sexual abuse or neglect) associated with significantly higher body mass index (BMI) scores in adulthood (p <
0.05)
Reference Obesity (Silver Spring) 2009 Oct;17(10):1900
women who had childhood sexual abuse significantly more likely to be obese by age 2027 years
based on prospective case series of 84 women with substantiated childhood sexual abuse and 89 demographically similar controls
42% women who were abused and 28% controls were obese by age 2027 years
Reference Pediatrics 2007 Jul;120(1):e61
Possible risk factors
Dietary behaviors
certain beverages
possible increased risk for obesity with sugary drinks(1)
sugary drink consumption may be associated with increased likelihood of obesity, weight gain, and energy intake in adults (level 2 [midlevel]
evidence)
based on systematic review without assessment of trial quality
review of 88 trials and observational studies assessing association between sugary drink consumption and nutrition and health outcomes
sugary drink consumption associated with
small but significant (p < 0.05) increased weight in adults in analyses of
5 trials
3 longitudinal studies
5 crosssectional studies
small but significant (p < 0.05) increased energy intake in adults in analyses of
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11 trials
3 longitudinal studies
2 crosssectional studies
Reference Am J Public Health 2007 Apr;97(4):667 fulltext, commentary can be found in Evid Based Nurs 2007 Oct;10(4):120 fulltext
conflicting evidence associating sugary drink consumption with increased likelihood of obesity or weight gain in adults after adjusting for total
energy intake
review of 14 observational studies assessing association between sugary drink intake and likelihood of obesity or weight gain after adjusting for
total energy intake
in 6 studies assessing association in adults
significant association in 1 prospective cohort and 2 crosssectional studies
significant association in women but not men in 1 crosssectional study
no significant association in 2 crosssectional studies
significant association in 1 prospective cohort study and 1 crosssectional study that adjusted for energy intake from nonsugary drinks
Reference Nutr Rev 2014 Sep;72(9):566
increase in sugary drink intake from childhood to adulthood associated with increased risk of being overweight or obese in Finnish women but
not men (level 2 [midlevel] evidence)
2139 (55% women) persons in Finland were assessed with physical exams and questionnaires as children or adolescents in 1980 and at 21year
followup (Cardiovascular Risk in Young Finns Study)
prevalence of being overweight or obese
at first assessment, 7.8% of males and 7.8% of females
at 21year followup, 52% of males and 36.2% of females
increase in consumption of sugary drinks from childhood to adulthood associated with increased risk of being overweight or obese in women in
multivariate analyses (odds ratio 1.9, 95% CI 1.382.61)
no association between risk of being overweight or obese in adulthood and
increase in consumption of sugary drinks from childhood to adulthood in men
increase in consumption of sweets from childhood to adulthood in women or men
frequency of childhood consumption of sweets or sugary drinks in women or men
Reference Public Health Nutr 2009 Nov;12(11):2018
alcohol consumption appears not to affect body composition in adults (level 2 [midlevel] evidence)
based on systematic review of trials with incomplete assessment of trial quality and of observational studies
review of 31 studies (4 trials, 27 observational studies) assessing effect of alcohol consumption on body composition
method of randomization, blinding, or allocation concealment in trials not assessed
no effect of alcohol consumption on weight change found in 4 randomized trials of 812 weeks with 124 adults
conflicting results in associating alcohol consumption with
body mass index in 9 prospective cohort studies
waist circumference or waisttohip ratio in 4 prospective cohort studies
body mass index or weight gain in 14 crosssectional studies
Reference Nutr Rev 2011 Aug;69(8):419
eating behavior
eating until full and eating quickly may be associated with being overweight
based on crosssectional study in Japan
3,287 adults aged 3069 years completed surveys on cardiovascular risk in 20032006
selfreported eating until full in 50.9% men and 58.4% women
selfreported eating quickly in 45.6% men and 36.3% women
highest mean values for height, weight, body mass index, and total energy intake associated with eating until full and eating quickly compared to those
not reporting these behaviors
Reference BMJ 2008 Oct 21;337:a2002 fulltext, editorial can be found in BMJ 2008 Oct 21;337:a1926
large portion size(1)
exposure to large portion size meals reported to result in sustained increases in intake
based on cohort study of 19 patients exposed to small vs. large portion size meals each for 1 month
Reference Int J Behav Nutr Phys Act 2007 Jun 27;4:27 fulltext
Socioeconomic factors
risk of overweight associated with certain aspects of socioeconomic status in France
based on analysis of 2,413 adults aged 1874 years from crosssectional national French survey in 20062007
socioeconomic status based on occupation, education, and frequency of holiday trips (as indicator of family income)
overweight in 49.3% and obesity in 16.9%
risk of overall overweight or obesity significantly associated with
in men
occupation of selfemployed farmer
no holiday trip in past year lasting ≥ 4 nights (previously shown to be marker for higher income)
in women
less than a high school education
no holiday trip in past year lasting ≥ 4 nights
Reference BMC Public Health 2009 Jul 2;9:215 fulltext
overweight associated with lower socioeconomic position in United Kingdom but higher socioeconomic position in Brazil
based on 2 large cohorts from Brazil and United Kingdom
Reference BMC Public Health 2009 Apr 15;9:105 fulltext
Childhood obesity
obesity at 7 years old associated with increased risk of obesity in adulthood (level 2 [midlevel] evidence)
systematic review of 95 prospective cohort studies evaluating obesity in childhood or adolescence and association with obesity and/or development of
obesityrelated diseases in adulthood
23 studies evaluated association between obesity in childhood/adolescence and obesity in adulthood
obesity (≥ 95th centile or > 30 kg/m2 body mass index [BMI]) at ≥ 7 years old associated with increased obesity in adulthood (relative risk 5.21, 95% CI 4.5
10/35
6.02) in analysis of 7 studies
Reference Health Technol Assess 2015 Jun;19(43):1 PDF
adolescent obesity associated with increased risk of severe obesity in adulthood
8,834 persons aged 1221 years were followed into adulthood (aged 2433 years)
79 (1%) adolescents severely obese (body mass index ≥ 30) at baseline (60 [70.5%] remained severely obese in adulthood)
703 (7.9%) nonseverely obese adolescents at baseline became severely obese in adulthood
adolescent obesity associated with increased risk of severe obesity in young adulthood (hazard ratio 16 [95% CI 12.420.5] vs. normal weight or overweight
[BMI < 30])
Reference JAMA 2010 Nov 10;304(18):2042 fulltext
obesity in childhood and adolescence may be associated with obesity in adulthood
birth cohort of 1,142 infants with 412 evaluated at all followup points (aged 9, 13, and 50 years)
increasing BMI percentile associated with greater incidence of adult obesity
Effect of Childhood Body Mass Index on Adult Obesity:
9 Years Old 13 Years Old
BMI < 25th 25th75th
75th90th percentile > 90th percentile < 25th percentile 25th75th percentile 75th90th percentile > 90th percentile
group percentile percentile
Incidence
of adult 8% 12% 28% 42% 5% 14% 22% 45%
obesity
P value
< 0.001 (pairwise comparisons not reported) < 0.001 (pairwise comparisons not reported)
for trend
Abbreviation: BMI, body mass index.
no significant correlation between
childhood obesity and adult body fat percentage
childhood overweight and adult obesity
Reference BMJ 2001 Dec 1;323(7324):1280 fulltext, commentary can be found in BMJ 2002 Mar 16;324(7338):676
52% of children with obesity had obesity in adulthood
birth cohort of 16,567 infants with 8,490 (51%) having BMI data at ages 10 and 30 years
prevalence of obesity 4.3% at age 10 years and 16.3% at age 30 years
52% of children obese at age 10 years were obese at age 30 years
Reference BMJ 2005 Jun 11;330(7504):1354 fulltext, editorial can be found in BMJ 2005 Jun 11;330(7504):1339 fulltext
parental obesity during childhood and patient obesity at age ≥ 3 years are associated with increased risk of obesity during young adulthood (level 2 [mid
level] evidence)
854 adults' and their parents' heights and weights were assessed from medical records in Washington state, United States
all adults were born 19651971 and were aged 2129 years at time of study
adults excluded if they had a chronic condition that may affect height or weight or were born at < 36 weeks gestational age
adult obesity defined as mean body mass index in adulthood ≥ 27.8 kg/m2 for men and 27.3 kg/m2 for women
obesity in 16% of adults
Risk of Obesity in Adulthood in Multivariate Analysis:
1 Parent Obese During 2 Parents Obese During Childhood
Childhood Age Obesity During Childhood Age*
Childhood Age** Age**
12 years No increased risk OR 3.2 (95% CI 1.85.7) OR 13.6 (95% CI 3.750.4)
1014 years OR 22.3 (95% CI 10.547.1) OR 2.2 (95% CI 1.23.8) No increased risk
Abbreviation: OR, odds ratio.
* Odds ratio in comparison to no obesity during childhood age.
** Odds ratio in comparison to 0 parents obese during childhood age.
Reference N Engl J Med 1997 Sep 25;337(13):869 fulltext, editorial can be found in N Engl J Med 1997 Sep 25;337(13):926 fulltext
conflicting evidence associating infant size with obesity in adulthood
review of 24 observational studies (22 cohort, 2 case control) assessing association between infant size or growth and subsequent obesity
significant heterogeneity between studies, particularly in how infant size was assessed
larger infant size associated with obesity in adulthood in 3 of 7 studies that assessed infant size and obesity in adulthood
Reference BMJ 2005 Oct 22;331(7522):929 fulltext, commentary can be found in BMJ 2005 Nov 12;331(7525):1145 fulltext
Birth delivery mode
cesarean section associated with overweight and obesity in offspring (level 2 [midlevel] evidence)
systematic review of 7 prospective cohort studies and 2 casecontrol studies evaluating association of cesarean section delivery with offspring obesity in
245,477 patients ≥ 3 years old
compared to vaginal birth, cesarean section associated with increased overweight/obesity in
overall patient population (odds ratio [OR] 1.33, 95% CI 1.191.48) in analysis of 9 studies, results limited by significant heterogeneity
children aged 38 years (OR 1.32, 95% CI 1.151.51) in analysis of 8 studies
11/35
adolescents aged 918 years (OR 1.24, 95% CI 11.54) in analysis of 2 studies
adults (OR 1.5, 95% CI 1.022.2) in analysis of 3 studies
Reference Int J Obes (Lond) 2013 Jul;37(7):893
mode of delivery not associated with likelihood of obesity at age 21 in cohort study of 2,625 adults in Australia (Obstet Gynecol 2013 Dec;122(6):1176)
Gut microbiota
gut microbiota influences energy and nutrient extraction through multiple pathways
certain microbes ferment some nonabsorbable complex nutrients into absorbable shortchain fatty acids
energy balance of host with less diverse microbiota may be less resilient to changes in microbiota
factors that may influence microbiota composition include
antibiotic exposure (particularly in early life)
dietary changes including diet composition and caloric intake
anatomical rearrangements of gastrointestinal tract
gastrointestinal illness
mother's microbiota (which influences founding microbiota)
delivery method (vaginal vs. Caesarian section) (which influences founding microbiota)
Reference Cell Metab 2013 Jun 4;17(6):883 fulltext
apparent differences in gut microbiota in persons with obesity compared to healthy body mass index, but specific characteristics are not consistent between studies
obesity associated with greater proportions of gut microbiota that are Bacteroidetes and lower proportions that are Firmicutes, and greater total
shortchain fatty acid concentration in gut, in adults in Germany
based on case control study
98 persons ≥ 14 years old (mean age 47 years) in Germany had gut microbiota characterized with 16S ribosomal RNA polymerase chain reaction
sequencing of fecal samples
33 with obese, 35 with overweight (but not obese), and 30 with healthy body mass index
persons did not take antibiotics during prior 6 months
Firmicutes (Clostridium leptum and Clostridium coccoides) and Bacteroidetes (Bacteroides) comprised median 96.3% of gut microbiota
in adults with obese vs. healthy body mass index
bacteria concentrations
median percentage of microbiota that are Bacteroidetes 45% vs. 22.9% (p < 0.05)
median percentage of microbiota that are Firmicutes 51% vs. 73.1% (p < 0.05)
lower median concentrations of C. leptum, Ruminococcus flavefaciens, Bifidobacterium, and Methanobrevibacter (p < 0.05 for each)
no significant differences in median concentrations of C. coccoides, Lactobacillus , Enterococcus, Eubacterium cylindroids, Veillonella,
Bacteroides, Prevotella
shortchain fatty acid concentrations
total shortchain fatty acid concentration 103.9 vs. 84.6 mmol/L (p < 0.05)
propionate fatty acid concentration 19.3 vs. 13.6 mmol/L (p < 0.05)
no significant differences in
concentration of nonpropionate fatty acids including acetate, isobutyrate, butyrate, isovalerate, and valerate
gross energy content of fecal sample
Reference Obesity (Silver Spring) 2010 Jan;18(1):190
obesity associated with less diverse gut microbiota, and lower proportion of microbiota that are Bacteroidetes and greater proportion that are
Actinobacteria, in adult women in United States
54 female twin pairs (31 monozygotic, 23 dizygotic) 2532 years old in United States with European and African ancestry had gut microbiota
characterized with 16S ribosomal RNA polymerase chain reaction sequencing and multiplex pyrosequencing of fecal samples
all but 1 twin pair were concordant for overweight/obese vs. healthy BMI
twins did not take antibiotics for mean 5.5 months
compared to women with obesity, women with healthy BMI had
less phylogenetic diversity (p < 0.05)
lower proportion of microbiota that were Bacteroidetes (p = 0.003 in analysis combining data from 4 sequencing methods)
greater proportion of microbiota that were Actinobacteria (p = 0.002 in analysis combining data from 4 sequencing methods)
similar amount of Firmicutes (in analysis combining data from 4 sequencing methods)
Reference Nature 2009 Jan 22;457(7228):480 fulltext, commentary can be found in Nat Biotechnol 2009 Apr;27(4):344
obesity associated with lower gut Bacteroidete concentrations and possibly higher Lactobacillus in persons in France
49 persons in France had gut microbiota characterized with 16S ribosomal RNA polymerase chain reaction sequencing of fecal samples
20 (aged 1772 years) had obese BMI, 20 (aged 1368 years) had healthy BMI, and 9 (aged 1936 years) were diagnosed with anorexia nervosa
mean Bacteroidetes concentration 0.4 × 1010 copy number in adults with obese BMI and 1.3 × 1010 in adults with healthy BMI (estimated from figure)
(p < 0.01)
no significant differences between adults with obese and healthy BMI in mean concentration of
Lactobacillus, but ≥ 106 copy numbers in 40% of persons with obese and 5% of persons with healthy BMI (p = 0.0197)
Methanobrevibacter smithii
Reference PLoS One 2009 Sep 23;4(9):e7125 fulltext
obesity associated with greater likelihood of gut Lactobacillus reuteri and healthy body mass index associated with gut Methanobrevibacter smithii in
adults in France
115 adults (68 with obese BMI) in France had gut microbiota characterized with polymerase chain reaction sequencing of fecal samples and cultures
(with Lactobacillusspecific medium)
adults did not take antibiotics or have diarrhea during prior month or have history of gastric bypass, colon cancer, or inflammatory bowel disease
adults with overweight but not obese BMI were excluded
in analyses based on polymer chain reaction results
factors associated with likelihood of obesity in multivariate analysis include
presence of L. reuteri (odds ratio [OR], 95% CI 1.033.1)
presence of M. smithii (OR 0.76, 95% CI 0.590.97)
increasing age (OR 1.05, 95% CI 1.011.08)
presence of Bifidobacterium animalis might be less likely in adults with obesity (OR 0.63, 95% CI 0.391.01)
presence of Lactobacillus casei/paracasei and Lactobacillus gasseri not associated with likelihood of obesity in multivariate analysis
in analyses based on culture (with Lactobacillusspecific medium)
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presence of L. paracasei less likely in adults with obese BMI in ageadjusted multivariate analysis (OR 0.79, 95% CI 0.640.97)
L. reuteri, Lactobacillus plantarum, Lactobacillus brevis, and Lactobacillus fermentum not associated with likelihood of obesity in multivariate
analysis
Reference Int J Obes (Lond) 2012 Jun;36(6):817 fulltext
Infection
adenovirus 36 infection associated with increased likelihood of obesity, but association might be limited to children
based on 2 systematic reviews of case control and crosssectional studies
review of 11 case control or crosssectional studies with 5,513 persons assessing association between adenovirus 36 (Ad36) infection and obesity
Ad36 infection
associated with increased likelihood of obesity in children in analysis of 4 studies with 913 children
odds ratio (OR) 1.95 (95% CI 1.342.85)
NNH 522 with Ad36 infection in 16.3% of nonobese children
not associated with likelihood of obesity in adults (OR 1.44, 95% CI 0.952.18) in analysis of 7 studies with 4,600 adults (results limited by
heterogeneity)
Reference Obesity (Silver Spring) 2014 Mar;22(3):895
review of 10 case control or crosssectional studies with 2,870 persons assessing association between Ad36 infection and BMI and/or obesity
Ad36 infection
associated with increased likelihood of obesity in analysis of 7 studies with 2,489 persons (including 2 studies with 442 children) (odds ratio
[OR] 1.9, 95% CI 1.013.56)
associated with increased BMI in adults in analysis of 7 studies with 2,051 adults (mean difference 3.18, 95% CI 0.785.57)
Toxoplasma gondii associated with obesity in adults
999 adults in Munich, Germany without history of psychiatric disorders were assessed for T. gondii seropositivity and body composition
seropositive T. gondii determined if T. gondii immunoglobulin G antibody titer ≥ 0.8
obesity in 10.7% with and 4.2% without seropositive T. gondii (no p value reported)
seropositive T. gondii associated with increased likelihood of obesity (odds ratio 1.97, 95% CI 1.153.39, in ageadjusted analysis)
Reference Front Public Health 2013;1:73 fulltext
Brown adipose tissue and coldinduced thermogenesis
brown adipose tissue (BAT) may increase resting energy expenditure, especially through nonshivering coldinduced thermogenesis (Ann N Y Acad Sci 2013
Oct;1302:1 fulltext)
high body mass index associated with low coldinduced brown adipose tissue activity (level 2 [midlevel] evidence)
based on 2 cohort studies
brown adipose tissue activity assessed with 18Ffluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT)
24 men without health problems were assessed during thermoneutral conditions (22 degrees C [72 degrees F]) for 1 hour and mild cold conditions (16
degrees C [61 degrees F]) for 2 hours
14 men had overweight or obese BMI
coldinduced BAT activity was 102 kilobecquerels in men with overweight or obese BMI and 428 kilobecquerels in men with healthy BMI (p = 0.007)
Reference N Engl J Med 2009 Apr 9;360(15):1500 fulltext, correction can be found in N Engl J Med. 2009 Apr 30;360(18):1917, editorial can be
found in N Engl J Med 2009 Apr 9;360(15):1553 fulltext, extensive commentary can be found in N Engl J Med 2009 Jul 23;361(4):415
15 adults (3 women) with morbidly obese BMI but without diabetes or betablocker use were assessed during thermoneutral conditions (mean 22.3 degrees C
[72.1 degrees F]) for 1 hour and mild cold conditions (just above shivering, individualized for each person, mean temperature < 15 degrees C [59 degrees F])
for 2 hours
resting metabolic rate measured with indirect calorimetry
detectable coldinduced BAT activity in 3 adults
in analyses combining data from current study with 24 men from previous study (N Engl J Med 2009 Apr 9;360(15):1500)
high BMI associated with low BAT activity in correlational analyses
resting metabolic rate after cold exposure 51.5 joules/second for adults with and 44 joules/second for adults without detectable BAT activity (p =
0.001)
Reference PLoS One 2011 Feb 24;6(2):e17247 fulltext
possible increased likelihood of low body mass index among adults with brown adipose tissue, but low body mass index is not an independent predictor of
brown adipose tissue
1,972 adults who had 18Ffluorodeoxyglucose PET/CT from 2003 to 2006 were assessed for BAT
in 106 (5.4%) patients with detectable BAT, 40% had BMI < 23.5 kg/m2, 34% had BMI 23.527.8 kg/m2, and 28% had BMI > 27.8 kg/m2 (p < 0.04, pairwise
statistical comparisons not reported)
factors associated with increased likelihood of BAT in multivariate analysis include
female gender
age > 60 years old compared with age < 50 years old
no use of betablockers
factors not associated with increased likelihood of BAT in multivariate analysis include BMI < 23.5 kg/m2, fasting glucose levels, presence of cancer, history
of smoking, and benzodiazepine use
Reference N Engl J Med 2009 Apr 9;360(15):1509 fulltext, editorial can be found in N Engl J Med 2009 Apr 9;360(15):1553 fulltext, extensive
commentary can be found in N Engl J Med 2009 Jul 23;361(4):415
Associated conditions
prediabetes
metabolic syndrome
28% prevalence of polycystic ovary syndrome reported in 113 overweight or obese women in Spain referred to endocrinology department for dietary treatment
(Arch Intern Med 2006 Oct 23;166(19):2081)
genetic syndromes associated with obesity include
PraderWilli syndrome
Laurence Moon Bardet Biedl syndrome (Mymensingh Med J 2009 Jan;18(1 Suppl):S124, JNMA J Nepal Med Assoc 2008 OctDec;47(172):235)
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Etiology and Pathogenesis
Causes
positive energy imbalance increased energy intake and/or decreased energy expenditure in relation to each other(1)
5060 calories per day in excess (due to increased intake and/or decreased expenditure) for 1 year reported to result in > 5.3 lbs (2.4 kg) increase in weight(1)
increased risk of obesity with decreased socioeconomic status in developed countries may be due in part to(1)
lower consumption of healthy foods
lack of access to sports facilities and lower participation in sports
lower physical activity outside of work
Pathogenesis
positive energy imbalance results in weight gain(1)
possible causes of positive energy imbalance are not wellunderstood and are likely different for different people(1)
much information is from preclinical studies involving animals as well as humans(3)
homeostatic mechanisms adjust feeding behavior based on energy and nutritional needs of body, communicated in part through hormones (Nat Rev
Endocrinol 2014 Sep;10(9):540)
hedonic mechanisms adjust feeding behavior based on hedonic effects of food intake (Nat Rev Endocrinol 2014 Sep;10(9):540)
"setpoint theory" of body weight regulation and obesity theoretical framework sometimes used to explain how different factors influence feeding behavior
difference between predetermined constant "preferred" body weight and current weight modifies eating behavior and/or physical activity through
several feedback control systems including
response of gastrointestinal satiety signalproducing organs to food and nutrient levels
response of brain areas such as hypothalamus to gastrointestinal satiety signals and environmental stimuli
genetics partly determines response of gastrointestinal organs and related brain areas
modern (especially Western) diet and lifestyle may overly activate signals promoting orexigenic behavior but not anorectic behavior
References
F1000 Med Rep 2010 Aug 9;2:59 fulltext
FASEB J 1990 Dec;4(15):3310 PDF, commentaries can be found in FASEB J 1992 Jan 6;6(2):794 PDF, FASEB J 1991 Apr;5(7):2105 PDF
Metab Syndr Relat Disord 2011 Apr;9(2):85
leptin may have anoretic effects in part through influence on arcuate nucleus of hypothalamus and other brain areas(3)
leptin secreted by white adipose tissue in proportion to triglyceride volume
serum levels associated with decreased food intake and increased energy expenditure
encoded by ob gene
leptin interaction with arcuate nucleus of hypothalamus associated with decreased food intake
leptin excites proopiomelanocortin (POMC) and cocaine and amphetamineregulated transcript (CART) neurons (which inhibit food intake and
increase energy expenditure through downstream excitation of melanocortin receptors)
leptin inhibits neuropeptide Y (NPY) neurons (which stimulate food intake)
leptin inhibits agoutirelated peptide (AgRP) neurons (which stimulate food intake through downstream inhibition of melanocortin4 receptors)
other areas of the brain in which leptin exposure is associated with decreased food intake or increased energy expenditure include
other areas of hypothalamus
ventromedial nucleus of hypothalamus
lateral hypothalamic area
ventral tegmental area
nucleus of the solitary tract (leptin excites POMC neurons)
dorsal motor nucleus of vagus
third and fourth ventricles
leptin may also increase anorectic effects of cholecystokinin (CCK)
obesity may be due in part to decreased sensitivity to leptin levels (leptin resistance)
References
Exp Diabetes Res 2012;2012:824305 fulltext
J Clin Invest 2011 Jun;121(6):2087 fulltext
Trends Endocrinol Metab 2010 Nov;21(11):643 fulltext
other hormones that influence feeding behavior(3)
hormones that are associated with anoretic effects include
insulin
secreted by beta cells of the pancreas
serum levels increase postprandial
peptide tyrosine tyrosine (PYY)
secreted by Lcells of intestine
serum levels increase postprandial and decrease during fasting
obesity may be associated with lower than normal serum levels, particularly postprandial, but evidence is limited
also delays gastric emptying
pancreatic polypeptide (PP)
secreted by pancreatic polypeptide cells in pancreatic islets of Langerhans
serum levels decrease
postprandial (for up to 6 hours)
in the morning
with increased adipose tissue volume
obesity may be associated with lower than normal serum levels, but evidence is limited
also delays gastric emptying
glucagonlike peptide1 (GLP1)
serum levels increase postprandial and decrease during fasting
anorectic effect of increased serum levels may be decreased in obesity
also delays gastric emptying and decreases serum glucose levels through stimulation of insulin secretion
oxyntomodulin (OXM)
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may act via GLP1 receptors
also delays gastric emptying, decreases gastric acid secretion, and decreases serum glucose levels (though not as effectively as GLP1)
glucagon
secreted by alpha cells of pancreatic islets
increases serum glucose levels through increased hepatic glucose output
increases energy expenditure
glucagon levels increase in response to
stress
cold acclimatization
Reference Endocrinology 2012 Mar;153(3):1049 fulltext
cholecystokinin (CCK)
secreted by Icell of the small intestine
may act synergistically with leptin
amylin
secreted by beta cells of the pancreas (coreleased with insulin)
higher basal level in obese persons thought to decrease sensitivity to postprandial increase (Obes Res 2002 Oct;10(10):1087)
may also inhibit neuropeptide Y release and modulate serotonin, antihistamine, and dopamine systems
ghrelin associated with orexigenic effects
secreted from stomach
serum levels decrease postprandial and increase during fasting
obesity associated with reduced postprandial decrease
stimulates neuropeptide Y and agoutirelated peptide neurons in arcuate nucleus of hypothalamus
may also increase hedonic response to food intake
numerous areas of brain involved in appetite control
hypothalamus(3)
activation of neurons in hypothalamus expressing malanocortin4 receptor (MC4R) appear to inhibit food intake
CART in hypothalamus appears to increase or decrease food intake, depending on site of action
paraventricular nucleus
receives projections from arcuate nucleus neurons that express NPY, AgRP, POMC, or CART
appears to inhibit food intake
projects to many areas including ventral tegmental area, EdingerWestphal nucleus, ventrolateral periaqueductal gray matter, reticular formation,
pedunculopontine tegmental nucleus, dorsal raphe nucleus, prelocus coeruleus, nucleus ambiguous, and nucleus of the solitary tract
receives projections from neurons in arcuate nucleus of hypothalamus that express NPY, AgRP, POMC, or CART
contains neurons expressing melaninconcentrating hormone (MCH) and orexin (which stimulate food intake)
dorsomedial nucleus
receives projections from neurons in arcuate nucleus of hypothalamus that express NPY or AgRP
projects to paraventricular nucleus
appears to inhibit food intake in part through neurons expressing brainderived neurotrophic factor (BDNF)
ventromedial nucleus neurons expressing BDNF appear to inhibit food intake through activation of downstream MC4R
areas of hypothalamus involved with circadian rhythms influence areas of hypothalamus involved with feeding behavior
light calibrates "pacemaker" neurons in suprachiasmatic nucleus of hypothalamus, which projects to other areas of hypothalamus including
arcuate nucleus
paraventricular nucleus
dorsomedial hypothalamus
Reference J Clin Invest 2011 Jun;121(6):2133 fulltext
dorsal vagal complex of brainstem(3)
comprises dorsal motor nucleus of vagus, area postrema, and nucleus of the solitary tract (NST)
relays hormone and stretch signals from gut to hypothalamus and cortical areas, including through vagus nerve
NST
responds to gastric distention
receives projections from lateral hypothalamic area and ventromedial nucleus of hypothalamus
rewardmediating brain areas may influence feeding behavior through hedonic effects of food intake rather than satisfaction of energy requirements(3)
structures include
striatum of basal ganglia
includes ventral striatum and nucleus accumbens
muopioid receptor agonists in nucleus accumbens appear to
increase intake of highfat food
increase expression of orexin hypothalamus
act via cannabinoid receptors
dopamine neurons in ventral tegmental area and substantia nigra of basal ganglia
insular cortex
anterior cingulate cortex
orbitofrontal cortex (processes reward information and also gustatory, olfactory, visual, and somatosensory information)
preclinical animal and human studies suggest that rewardmediating brain areas may also be influenced by leptin, insulin, and ghrelin levels (Nat Rev
Endocrinol 2014 Sep;10(9):540)
possible increased risk of obesity associated with decreased volume of orbitofrontal cortex, left insula, and cerebellum (level 2 [midlevel] evidence)
53 nonobese adults (aged 2540 years) were empirically classified as "obese prone" or "obese resistant" and assessed with magnetic resonance imaging
(MRI)
obeseprone adults selfidentified as chronically struggling with body weight and have
body mass index (BMI) 2030 kg/m2
≥ 1 firstdegree relative with reported history of obesity
history of weight fluctuations of ≥ 10 pounds (4.54 kg)
weight stability for past 3 months
no current attempts at weight loss
obeseresistant adults selfidentified as being "naturally thin" and have
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BMI 1725 kg/m2
no firstdegree relatives with history of obesity
no history of being overweight
no history of weight fluctuations of ≥ 10 pounds (4.54 kg)
no history of weightloss attempts
≤ 3 hours/week of planned physical activity
comparing obeseprone vs. obeseresistant adults
BMI 26 vs. 21 kg/m2 (p < 0.001)
body fat mass 29% vs. 19% (p < 0.001)
serum leptin 11.4 vs. 3.9 mcg/L (p < 0.001)
obeseprone compared to obeseresistant adults had reduced gray matter (adjusted for age, gender, and total brain volume) in
orbitofrontal cortex (p < 0.001)
left insula (p < 0.001)
cerebellum (p < 0.001)
consistent results after adjusting for body fat mass and for subgroup of obeseprone adults with BMI ≤ 27 kg/m2
higher serum leptin levels associated with lower left insula gray matter volume in correlation analysis (p = 0.002)
men compared to women had reduced gray matter volume in left insula (p = 0.001) and cerebellum (p = 0.006)
Reference Appetite 2012 Dec;59(3):859 fulltext
decreased orbitofrontal cortex volume in overweight or obese adults may be associated with worse diet
139 adults (41 overweight or obese) were assessed with 3day food diary, MRI, and cognitive evaluations
highquality food score defined as sum of farm produce, fish, whole grains, and nuts
lowquality food score defined as sum of meat, refined carbohydrates, fried food, fast food, junk food, and alcohol
overweight or obese adults had significantly fewer education years and lower IQ scores than normal or low body mass index adults
comparing overweight or obese vs. normal or low body mass index adults
daily highquality food 4 vs. 5.3 items (estimated from figure) (p < 0.05)
daily lowquality food 5 vs. 4.1 items (estimated from figure) (p < 0.05)
decreased performance on several cognitive tests including Stroop test, Wisconsin Card Sorting Test, Trail Making Test, Digit Span, Visual
memory, and Digit Symbol Substitution (p < 0.05 for all)
increased highquality food score associated with increased orbitofrontal cortex volume (adjusted for head size) in overweight or obese adults (p =
0.01) but not in lean adults
Reference BMJ Open 2011 Jan 1;1(2):e000175 fulltext
History and Physical
History
Chief concern (CC)
body mass index ≥ 30 kg/m2(1, 4)
Medication history
ask about medication use that may produce weight gain(2)
Medications:
Type of Medication Medication Possible Alternate Medication
clozapine
haloperidol
olanzapine aripiprazole
Antipsychotics
quetiapine ziprasidone
risperidone
thioridazine
amitriptyline
doxepin bupropion
imipramine fluoxetine
Antidepressants mirtazapine nefazodone
nortriptyline protriptyline
paroxetine sertraline
phenelzine
carbamazepine lamotrigine
Anticonvulsants gabapentin topiramate
valproate zonisamide
acarbose
canagliflozin
dapagliflozin
exenatide
insulin liraglutide
Antidiabetics sulfonylureas metformin
thiazolidinediones miglitol
orlistat
pramlintide
sitagliptin
saxagliptin
inhalers
Antihistamines cyproheptadine
decongestants
propranolol angiotensinconverting enzyme
Beta or alphaadrenergic blockers inhibitors
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doxazosin calcium channel blockers
contraceptives
barrier prophylactics
Steroids glucocorticoids
NSAIDs
progestational steroids
Abbreviations: NSAIDs, nonsteroidal antiinflammatory drugs.
other drugs associated with weight gain include
pregabalin (CNS Drugs 2014 Sep;28(9):835)
zolpidem (due to sleeprelated eating disorder) (BMJ Case Rep 2013 Feb 21;2013: fulltext)
Past medical history (PMH)
ask about mood disorders and psychiatric history including(2)
binge eating
night eating syndrome
bulimia
depression
Family history (FH)
ask about family history of obesity(1)
Social history (SH)
assess current level of physical activity(2)
ask about possible behavioral and biopsychosocial risk factors for weight gain(1, 2)
smoking cessation
starting new medication
change in marital status
change in occupation
recent illness
pregnancy
menopause
stressful events
Physical
General physical
measure height and weight to calculate body mass index(1, 2, 3, 4)
measure waist and blood pressure to determine risk factors for complications such as metabolic syndrome (see also Complications of obesity)(2)
Diagnosis
Making the diagnosis
obesity usually defined as body mass index (BMI) ≥ 30 kg/m2(1, 4)
BMI = weight in kg divided by square of height in meters, or use BMI calculator
low weight: < 18.5 kg/m2
healthy weight: 18.524.9 kg/m2 (least risk of morbidity or mortality)
overweight (preobese): 2529.9 kg/m2
obese: ≥ 30 kg/m2
class I: 3034.9 kg/m2
class II: 3539.9 kg/m2
class III (extreme obese): ≥ 40 kg/m2
additional considerations
BMI does not directly measure adiposity
if BMI < 35 kg/m2, consider also using waist circumference
BMI ≥ 50 kg/m2 sometimes referred to as "super obese" (Public Health 2007 Jul;121(7):492 fulltext)
if patient highly muscular, implications of BMI estimate is less clear
risk of comorbidity for given BMI
higher for Asian adults
lower for older people
use age and genderadjusted BMI for children
alternative method of classification for adults is based on waist circumference (measured at iliac crest of pelvis), may be particularly useful if BMI < 35 kg/m2(1, 2)
low
< 37 inches (94 cm) for men
< 31.5 inches (80 cm) for women
high
≥ 37 inches (94 cm) for men
≥ 31.5 inches (80 cm) for women
very high
≥ 40.2 inches (102 cm) for men
≥ 34.6 inches (88 cm) for women
increased health risk if waisttohip circumference ratio
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> 1 for men
> 0.85 for women
Testing overview
tests that may be useful for identifying complications of obesity
lipid profile to identify hyperlipidemia
total cholesterol
highdensity lipoprotein (HDL) cholesterol
triglycerides
fasting blood glucose or oral glucose tolerance test to identify prediabetes, diabetes, or metabolic syndrome
liver enzymes to screen for nonalcoholic steatohepatitis
complete blood count
polycythemia may be seen with alveolar hypoventilation syndrome with resulting right heart failure
thyroidstimulating hormone (TSH) to identify hypothyroidism
Reference Am Fam Physician 2002 Jan 1;65(1):81 fulltext
bioimpedance
use of bioimpedance to estimate adiposity not recommended by National Institute for Care Excellence (NICE)(1)
bioimpedance was found to be less inferior to body mass index (BMI) for predicting components of metabolic syndrome in crosssectional study (Obes Res
Clin Pract 2013 JanFeb;7(1):e55)
metabolic markers for insulin resistance in overweight adults without diabetes include triglyceride, triglyceride/highdensity lipoprotein (HDL)
cholesterol ratio, and insulin
258 overweight adult volunteers without diabetes were evaluated
insulin resistance defined as being in top tertile of steady state plasma glucose concentrations
optimal cutpoints associated with
67% sensitivity and 71% specificity for triglyceride > 130 mg/dL (1.47 mmol/L)
64% sensitivity and 68% specificity for triglyceride/HDL cholesterol ratio > 3 (1.8 in SI units)
57% sensitivity and 85% specificity for insulin > 109 pmol/L
Reference Ann Intern Med 2003 Nov 18;139(10):802, commentary can be found in Ann Intern Med 2004 Aug 3;141(3):243
DynaMed commentary clinical benefit from diagnosing insulin resistance has not been established, but preventive measures for diabetes mellitus type 2
might be considered and weight reduction has been shown to reduce insulin resistance
Treatment
Treatment overview
weight loss of 5%15% may greatly reduce complications in obese or overweight persons(2)
diet and exercise are primary strategies for losing weight
caloric expenditure must exceed caloric intake for any diet to be effective
adults can lose 12 lbs/week (0.450.91 kg/week) by consuming 5001,000 fewer kcal/day
most diets have good shortterm results but limited longterm efficacy (patients typically lose 5% of body weight over first 6 months, then return to
baseline weight by 1224 months)
effective diets include portion control plate (level 1 [likely reliable] evidence), lowfat diet (level 2 [midlevel] evidence), Mediterranean diet (level 1
[likely reliable] evidence), lowcarbohydrate diet (level 2 [midlevel] evidence), low glycemic index diet (level 2 [midlevel] evidence), and
commercial weightloss diets (level 2 [midlevel] evidence)
limited and inconsistent evidence on efficacy of olestra for weight loss
exercise may promote weight loss, especially when combined with dietary change (level 2 [midlevel] evidence)
multiple shortbout exercise (four 10minute sessions/day 5 days/week) might be equivalent to longbout exercise (40minute sessions 5 days/week)
(level 2 [midlevel] evidence)
regular exercise (brisk walking) slightly reduces body weight and body fat in postmenopausal women (level 1 [likely reliable] evidence)
low amount of exercise (walking 30 minutes/day) appears adequate to avoid weight gain and higher amounts promote weight loss (level 2 [midlevel]
evidence)
behavioral and cognitivebehavioral strategies associated with small reduction in body weight in obese or overweight (level 2 [midlevel] evidence)
acupuncture associated with significant weight loss in obese patients compared with placebo and conventional treatments (level 2 [midlevel] evidence)
medications (as adjunct to diet, physical activity, and behavior therapy)
orlistat (Xenical) 120 mg orally 3 times daily with meals containing fat, may be taken during or up to 1 hour after meal, skip dose if meal skipped
orlistat appears modestly effective with mean difference in weight loss 2.9 kg (6.4 lbs) (level 2 [midlevel] evidence)
halfstrength orlistat (Alli) may be modestly effective in helping mildlytomoderately overweight patients lose weight (level 2 [midlevel] evidence)
gastrointestinal side effects (oily spotting, flatus with discharge, fecal urgency, fecal incontinence) may be reduced by increasing fiber intake (including
use of psyllium) and decreasing dietary fat
lorcaserin (Belviq) 10 mg orally twice daily may increase weight loss in adults (level 2 [midlevel] evidence)
phentermine plus extendedrelease topiramate combination (Qsymia) 7.5 mg/46 mg orally once daily may increase weight loss in adults (level 2 [midlevel]
evidence)
metformin may be associated with small amount of weight loss (level 2 [midlevel] evidence), but insufficient evidence to support use of metformin in
overweight or obese adults without diabetes mellitus or polycystic ovary syndrome
nonprescription weightloss medications and supplements not recommended
multicomponent weightloss programs might be effective for weight loss in adults (level 2 [midlevel] evidence); maintenance interventions with behavioral and/or
lifestyle components may promote further weight loss for up to 18 months in overweight and obese adults (level 2 [midlevel] evidence)
surgery
bariatric surgery
consider bariatric surgery for patients with body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with comorbidities (BMI 3034 kg/m2 with
comorbidities in some cases)
compared to nonsurgical management bariatric surgery associated with (level 2 [midlevel] evidence)
reduced mortality
longterm weight loss (maintained up to 10 years)
reductions in comorbidities such as diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea
improved fertility in women with fewer maternal and neonatal complications
liposuction reported to reduce body mass index but not most risk factors for coronary heart disease or mediators of inflammation within 12 weeks in adult
18/35
women with obese body mass index with or without type 2 diabetes (level 3 [lacking direct] evidence)
see also
Obesity in children and adolescents
Physical activity for weight loss
Weightloss medications for obesity in adults
Weightloss nonprescription medications and supplements
Bariatric surgery
Diet
diet and exercise are 2 primary strategies that may be considered for weight loss
Academy of Nutrition and Dietetics (AND) recommends optimal rate of weight loss 12 lbs/week (0.450.91 kg/week); set initial weightloss goal of up to 10% of
body weight (3%5% of body weight if cardiovascular risk factors present) (AND Strong Recommendation)
caloric expenditure (including resting metabolic rate, thermic effect of feeding, and physical activity) must exceed caloric intake for any diet to be effective
adults can lose 12 lbs/week (0.450.91 kg/week) by consuming 5001,000 fewer kcal/day
reducedcalorie diets associated with similar reductions in body weight at 2 years in overweight adults regardless of macronutrients composition (level 2
[midlevel] evidence)
most diets have good shortterm results but limited longterm efficacy (patients typically lose 5% of body weight over first 6 months, then return to initial weight by
1224 months)
portion control plate promotes modest weight loss in obese patients with type 2 diabetes (level 1 [likely reliable] evidence)
lowfat diet appears effective for weight loss (level 2 [midlevel] evidence)
lowcarbohydrate diets
"lowcarb" diet may be interpreted in many ways because there is no standard definition
lowcarbohydrate, highprotein diets associated with more weight loss than diets with same energy intake but higher percentage of energy from carbohydrates
Mediterranean diet or lowcarbohydrate diet each appear more effective for modest longterm weight loss than lowfat diet (level 2 [midlevel] evidence)
lowcarbohydrate diets appear to reduce weight more than lowfat diets at 6 months but not at 12 months (level 2 [midlevel] evidence)
lower carbohydrate intake and higher protein intake associated with increased mortality in observational study (level 2 [midlevel] evidence)
dietary counseling associated with modest weight loss with decreased efficacy over time (level 2 [midlevel] evidence)
commercial weightloss diets appear modestly effective but evidence for comparative efficacy is inconsistent (level 2 [midlevel] evidence)
specific foods and food types
dietary advice to increase vegetable and fruit intake may contribute to weight loss (level 2 [midlevel] evidence)
increased intake of highfiber, wholegrain foods associated with weight loss (level 2 [midlevel] evidence)
energyrestricted diet containing fish or fish oil may further reduce weight compared to energyrestricted diet alone for overweight and moderately obese men
reduction of sugarsweetened beverage intake associated with weight loss (level 2 [midlevel] evidence)
addition of green tea to Thai diet associated with weight loss (level 2 [midlevel] evidence)
see Diets for weight loss for details
Drinking water
drinking 500 mL of water before meals associated with increased weight loss in obese adults (level 2 [midlevel] evidence)
based on randomized trial with low and differential adherence
84 obese adults (mean age 57 years, 64% women, mean body mass index [BMI] 34.1 kg/m2) randomized to drinking (still or tap) water 500 mL (17 ounces)
vs. imagining stomach was full (control) 30 minutes before main meals 3 times/day for 12 weeks
all patients had facetoface weight management consultation for 30 minutes and followup telephone consultation for 10 minutes at 2 weeks
comparing drinking water preload vs. control
≥ 5% reduction body weight in 27% vs. 5% (p < 0.05, NNT 5)
mean reduction in weight 2.4 kg (5.3 lbs) vs. 1.2 kg (2.6 lbs) (p = 0.028)
selfreported adherence 3 times daily at week 2 in 54% vs. 23% (no p value reported)
selfreported adherence 3 times daily at week 9 in 39% vs. 9% (no p value reported)
Reference Obesity (Silver Spring) 2015 Sep;23(9):1785
Olestra
Olestra is mixture of sucrose and fatty acid esters (sucrose polyester) which is neither digested nor absorbed
replacement of dietary fat with olestra may reduce weight (by up to 2.5 kg [5.4 lbs] over 9 months) and total body fat (level 2 [midlevel] evidence), based on single
trial with 45 persons and 20% dropout rate
olestracontaining corn or potato chips may increase frequency of bowel movements, but gastrointestinal symptoms do not affect or only slightly affect daily
activities in most people (level 1 [likely reliable] evidence)
multivitamin daily can prevent olestrainduced decreases in vitamins A and E but not olestrainduced decreases in serum betacarotene, lycopene, lutein, and
zeaxanthin (level 3 [lacking direct] evidence)
Activity
exercise with dieting
combination of caloriereduced lowfat diet plus aerobic exercise reduces weight and body fat compared to either intervention alone in overweight or obese
postmenopausal women (level 1 [likely reliable] evidence)
for sedentary or obese individuals, use of physical activity without additional dietary changes typically does not produce loss ≥ 3% of baseline body weight
weightloss programs targeting diet and exercise associated with modest weight reductions in elderly (level 2 [midlevel] evidence)
exercise in children and adolescents
school physical activity program associated with decreased frequency of overweight in schoolaged girls (level 2 [midlevel] evidence)
aerobic exercise of moderatetohigh intensity 155180 minutes/week may reduce body fat in overweight children (level 2 [midlevel] evidence)
exercise in adults
moderateintensity physical activity (such as brisk walking, gentle swimming) recommended (ACSM Evidence Category B)
19/35
< 150 minutes/week promotes minimal loss
> 150 minutes/week can result in loss of 23 kg (4.46.6 lbs)
> 225425 minutes/week can result in loss of 57.5 kg (1116.5 lbs)
high amount of exercise (jogging 20 miles/week) may promote weight loss (level 2 [midlevel] evidence)
exercise with vigorous intensity and/or high duration may be no more effective than moderate exercise for sustained weight loss (level 2 [midlevel]
evidence)
multiple shortbout exercise (four 10minute sessions/day 5 days/week) might be equivalent to longbout exercise (40minute session 5 days/week) (level 2
resistance training with or without diet restriction not effective for weight loss, but may improve cholesterol profile, insulin resistance, and blood pressure
(ACSM Evidence Category B)
for weight maintenance after weight loss, 200300 minutes/week physical activity recommended
lifestyle physical activity
lifestyle physical activity (for example, brisk walking, raking leaves, using stairs instead of elevator) may be as effective as structured exercise program in
promoting weight loss over 2 years (level 2 [midlevel] evidence)
stepping exercise during TV commercials associated with similar increase in activity level compared to walking 30 minutes ≥ 5 days/week in overweight and
obese adults (level 2 [midlevel] evidence)
in patients with type 2 diabetes, intensive lifestyle intervention may promote greater weight loss compared to diabetes support and education (level 2 [mid
level] evidence)
see Physical activity for weight loss for details
Counseling
General behavioral interventions
advise overweight and obese adults to participate in a comprehensive lifestyle program for ≥ 6 months to support adherence to a lower calorie diet and to increase
physical activity (AHA/ACC Class I, Level A)(4)
counsel overweight and obese adults with cardiovascular risk factors (such as high blood pressure, hyperlipidemia, and hyperglycemia) that lifestyle modifications
may result in modest, sustained weight loss of 3%5% (AHA/ACC Class I, Level A)(4)
sustained weight loss of 3%5% may result in clinically meaningful improvement in triglycerides, blood glucose, HbA1C, and risk of diabetes mellitus type 2
greater amounts of weight loss may reduce blood pressure, improve low and highdensity lipoprotein cholesterol, reduce need for medications to control
blood pressure, blood glucose, lipids, and further reduce triglycerides and blood glucose
prescribe comprehensive intervention which is highintensity (such as ≥ 14 sessions over 6 months), onsite, and delivered by trained professional in a group or
individual setting (AHA/ACC Class I, Level A)(4)
behavioral interventions associated with small reduction in body weight in obese or overweight adults (level 2 [midlevel] evidence)
based on systematic review with results of questionable clinical relevance
systematic review of 15 randomized trials with 4,539 patients comparing behavioral interventions vs. no behavioral intervention with ≥ 1year followup in
4,539 obese or overweight adults
interventions were heterogeneous in behavioral theories, components of interventions, and use of group vs. individual sessions
behavioral intervention associated with reduced weight
at 1 year (mean difference [MD] 1.36 kg [3 lbs], 95% CI 2.1 to 0.63 kg [4.6 to 1.4 lbs]) in analysis of 8 trials, results limited by significant
heterogeneity
at 2 years (MD 1.23 kg [2.7 lbs], 95% CI 2.28 to 0.18 kg [5 to 0.4 lbs]) in analysis of 5 trials, results limited by significant heterogeneity
Reference Fam Pract 2014 Dec;31(6):643 fulltext
similar results seen in Cochrane review (Cochrane Database Syst Rev 2005 Apr 18;(2):CD003818) withdrawn 2014 May 06 pending new review
behavioral lifestyle intervention for ≥ 32 sessions over 2 years may increase weight loss in obese adults in rural communities (level 2 [midlevel] evidence)
based on randomized trial with low adherence
612 obese adults (mean age 52 years, 78% women) in rural communities were randomized to behavioral lifestyle intervention (16 sessions vs. 32 sessions vs.
48 sessions) vs. control intervention for 16 sessions over 2 years
behavioral lifestyle intervention consisted of lowcalorie eating plan, increased physical activity, and training in behavior modification strategies
including goal setting, selfmonitoring, stimulus control, cognitive restructuring, and problem solving
control intervention consisted of nutrition education without instruction in behavior modification strategies
all interventions were divided into weightloss induction phase and targeted maintenance phase
mean body mass index (BMI) 36.3 kg/m2 and mean body weight 100.6 kg (221.8 lbs) at baseline
83.8% attended sessions during weightloss induction phase and 53.1% attended sessions during targeted maintenance phase
≥ 5% reduction in body weight in
43% with 16 sessions of behavioral lifestyle intervention (not significant vs. control)
58% with 32 sessions of behavioral lifestyle intervention (p < 0.05 vs. control, NNT 6)
58% with 48 sessions of behavioral lifestyle intervention (p < 0.05 vs. control, NNT 6)
40% with control intervention
Reference Rural LITE trial (Obesity (Silver Spring) 2014 Nov;22(11):2293)
behavioral treatment associated with modest efficacy for weight gain prevention in overweight and obese black women (level 2 [midlevel] evidence)
based on randomized trial with allocation concealment not stated
194 overweight and class 1 obese (BMI 2534.9 kg/m2) black women aged 2544 years randomized to behavioral treatment vs. usual care for 12 months
behavioral treatment included tailored behavior change goals, weekly selfmonitoring via interactive voice response, monthly counseling calls, tailored skills
training materials, and gym membership
comparing behavioral intervention vs. usual care
mean 12month weight change 1 kg (2.2 lbs) vs. + 0.5 kg (1.1 lbs) (p = 0.04)
percentage of women at or below baseline weight at 12 months 62% vs. 45% (p = 0.03, NNT 9)
mean 18month weight change 0.9 kg (2 lbs) vs. +0.8 kg (1.8 lbs) (p = 0.03)
Reference JAMA Intern Med 2013 Oct 28;173(19):1770, editorial can be found in JAMA Intern Med 2013 Oct 28;173(19):1778
behavioral factors associated with successful weight loss
based on mailed surveys completed by 6,207 United States residents reporting successful and unsuccessful weightloss attempts
weightloss strategies significantly more common among successful attempts
exercising > 30 minutes/day
adding physical activity to daily life
using fewer nonprescription diet products
meal planning on most days of the week (35.9% vs. 24.9%)
20/35
tracking calories (17.7% vs. 8.8%)
tracking fat (16.4% vs. 6.6%)
measuring food on the plate (15.9% vs. 6.7%)
weighing oneself daily (20.3% vs. 11%)
lifting weights (19% vs. 10.9%)
barriers reported that were associated with lower likelihood of successful weight loss
no time
too tired to exercise
no one to exercise with
too hard to maintain exercise routine
frequent eating away from home
expense of diet and health foods
Reference Int J Behav Nutr Phys Act 2006 Jul 19;3:17 fulltext
regular selfweighing might improve weight loss without increasing adverse psychological outcomes in overweight or obese adults (level 2 [midlevel]
evidence)
systematic review of 17 randomized trials and observational studies evaluating association between selfweighing and weight change in 10,040 overweight or
obese adults
followup range 16 weeks to 3 years
more frequent selfweighing associated with greater weight loss, less weight gain, and improved weight gain prevention in all studies, with varying effect
sizes across studies
frequent selfweighing not associated with adverse psychological outcomes (depression, anxiety) in 5 studies
Reference Obesity (Silver Spring) 2015 Feb;23(2):256
Individual counseling
individual counseling in primary care setting associated with modest weight loss and may be more effective with addition of pharmacotherapy (level 2
based on systematic review limited by heterogeneity
systematic review of 10 randomized trials evaluating obesity interventions in primary care setting in United States adults
metaanalysis not possible due to heterogeneity among trials, most trials provided low or moderateintensity counseling
weight loss based on type of intervention
0.12.3 kg (0.25 lbs) with primary care provider (PCP) counseling alone in 4 trials
1.77.5 kg (3.716.5 lbs) with PCP counseling plus pharmacotherapy in 3 trials
0.47.7 kg (0.916.9 lbs) with collaborative obesity care (treatment by nonphysician provider) in 3 trials
Reference J Gen Intern Med 2009 Sep;24(9):1073
behavioral counseling programs might promote weight loss in overweight and obese adults (level 2 [midlevel] evidence)
based on systematic review limited by clinical heterogeneity
systematic review of 12 randomized trials comparing behavioral counseling programs for weight loss vs. control in 3,893 overweight and obese patients
(mean age 4956 years)
all trials included counseling for ≥ 3 months and had ≥ 6 months of followup
programs varied in number of sessions, mode of contact (inperson, phone, online), number of care providers (primary care physician with or without
additional trained interventionist), and components included in counseling (diet, exercise, behavioral therapy)
no metaanalysis performed
mean weight change ranged from 6 kg (13.2 lbs) to 0.3 kg (0.6 lbs) in behavioral counseling arms and 2 kg (4.4 lbs) to +0.9 kg (+1.9 lbs) in control arms
Reference JAMA 2014 Nov 5;312(17):1779
stagesofchange model for lifestyle modification compared to usual care associated with small reduction in weight in overweight or obese adults (level 2
based on Cochrane review limited by clinical heterogeneity
systematic review of 3 randomized trials comparing stagesofchange model for lifestyle modification (such as changes in diet and physical exercise) to usual
care in 2,971 overweight or obese adults
trial duration was 924 months
metaanalysis precluded by differences in outcome measurements and followup duration
results for weight loss
stagesofchange model slightly increased weight loss compared to usual care (mean difference 2.12 kg [4.67 lbs], p < 0.05) in 1 trial with 1,277
adults
no significant difference in weight loss in 1 trial with 665 adults
patients in action stage of intervention group had greater weight loss compared to those in preaction stage of intervention group (mean difference 1.52
kg [3.35 lbs], p < 0.05), but no comparisons reported for intervention vs. usual care in 1 trial with 510 adults
stagesofchange model associated with
reduced mean daily caloric intake in 3 trials with 2,971 adults
increased physical activity in 2 trials with 1,932 adults
Reference Cochrane Database Syst Rev 2014 Feb 5;(2):CD008066
mindfulnessbased interventions might reduce or maintain weight and decrease obesityrelated eating behaviors (level 2 [midlevel] evidence)
review of 21 studies (8 randomized trials and 13 case series) assessing efficacy of mindfulnessbased interventions on obesityrelated eating behaviors
mindfulnessbased interventions included mindful eating, mindfulness meditation, mindful body scan, or acceptancebased practices
obesityrelated eating behaviors included binge eating, emotional eating, external eating, eating in response to food cravings, restrained eating,
mindless eating, and unhealthy dietary intake
overweight or obese patients in 12 (57%) studies
weight loss or maintenance reported in 9 of 10 studies that assessed weight
decreased obesityrelated eating behaviors after mindfulness intervention reported in
18 (86%) of all 21 studies
11 of 12 studies that assessed binge eating
5 of 8 studies that assessed emotional eating
4 of 6 studies that assessed external eating
2 of 3 studies that assessed dietary intake
Reference Obes Rev 2014 Jun;15(6):453
BeWEL program including diet plus physical activity counseling may promote weight loss in overweight and obese adults at risk for colorectal cancer
21/35
based on randomized trial with inadequate attention control
329 overweight or obese adults aged 5074 years (74% male, 14% with type 2 diabetes) attending routine colorectal cancer screening in Scotland were
randomized to 1 of 2 interventions for 1 year
BeWEL program
consisted of hourlong inperson motivational interviews with trained counselors 3 times over first 3 months, and then 15minute phone
conversations once monthly over last 9 months
participants set goal of 7% weight reduction and daily energy intake 600 kcals below that required for weight maintenance and selfmonitored
weight
control consisted of weightloss booklet
all patients had prior polypectomy for colorectal adenoma
93% who had 1year followup data available were included in analysis
comparing BeWEL program vs. control
mean weight loss 3.5 kg (7.7 lbs) vs. 0.78 kg (1.7 lbs) (p < 0.001)
≥ 7% weight loss in 22% vs. 9% (p < 0.05, NNT 8)
mean reduction in body mass index 1.22 kg/m2 vs. 0.27 kg/m2 (p < 0.001)
BeWEL program associated with significant reductions in systolic and diastolic blood pressure
no significant differences in cholesterol or triglyceride levels
Reference BMJ 2014 Mar 7;348:g1823 fulltext
Group counseling
groupbased cognitive behavior therapy lifestyle intervention may reduce weight in overweight or obese adults (level 2 [midlevel] evidence)
based on randomized trial with high dropout rate
191 adults (mean age 48 years) with overweight or obese body mass index were randomized to 1 of 3 groups
groupbased cognitive behavior therapy lifestyle intervention (Fat Booters Incorporated) weekly for 8 weeks, then monthly followup for 6 months and
followup at 12 months
individualized dietetic treatment weekly for 8 weeks, then monthly followup for 6 months and followup at 12 months
information booklet as control
53% of patients dropped out; 32% dropped out before receiving intervention
weight loss at 12month followup 2.9 kg (6.4 lbs) with groupbased cognitive therapy and 0.5 kg (1.1 lbs) with informational booklet in completer analysis
(p < 0.005)
individualized dietetic treatment did not differ significantly from control or from groupbased cognitive therapy
no significant differences between groups in body mass index, waist circumference, or percent body fat
Reference Int J Obes (Lond) 2006 Oct;30(10):1557
behavioral selfregulation intervention may improve longterm weight loss and weightloss maintenance in obese or overweight women (level 2 [midlevel]
evidence)
225 women (mean age 38 years) with overweight or mildly obese body mass index were randomized to behavioral selfregulation intervention (30 group
sessions) vs. general health education (control) for 12 months followed by 12month followup
psychosocial variables assessed with ThreeFactor Eating Questionnaire, SelfEfficacy for Exercise Behaviors scale, and Body Shape Questionnaire
dropout rate was 7% with intervention and 21% with control at 12 months (10% with intervention and 28% with control at 24 months) (no p values reported)
mean weight change in behavioral selfregulation intervention vs. control
7.3 kg (16.1 lbs) vs. 1.7 kg (3.8 lbs) at 12 months
5.5 kg (12 lbs) vs. 2.2 kg (4.9 lbs) at 24 months
lower emotional eating, increased flexible cognitive restraint, and fewer exercise barriers mediated 12month weight loss (p < 0.001)
behavioral selfregulation associated with improvement in all psychosocial variables at 12 months (p < 0.05 for all comparisons)
Reference Obesity (Silver Spring) 2010 Apr;18(4):725
culturallyadapted group weightloss program associated with weight reduction
culturally adapted group weightloss program associated with weight reduction for obese black women (level 2 [midlevel] evidence)
based on randomized trial without attention control
213 black women with obese body mass index were randomized to intervention vs. control
intervention group included twice weekly culturally adapted group weightloss meetings for 6 months
control group included general health advice in weekly emails and monthly phone calls
56%60% of patients in intervention attended ≥ 50% of meetings
mean weight change 3 kg (6.6 lbs) in intervention vs. +0.2 kg (+0.44 lbs) in control group (p < 0.001)
Reference ORBIT trial (Obesity (Silver Spring) 2009 Jan;17(1):100 fulltext)
similar findings at 18 months
based on 18month followup of randomized trial above
intervention associated with greater weight loss (adjusted mean difference 2.83 kg [6.2 lbs], p = 0.003)
weight loss of ≥ 5% from baseline in 24% with intervention vs. 12% controls (p < 0.04, NNT 9)
Reference Obesity (Silver Spring) 2010 Dec;18(12):2317 fulltext
intensive lifestyle intervention including culturally sensitive counseling and exercise may reduce weight and triglyceride and glucose levels in obese
Arabic women living in Israel (level 2 [midlevel] evidence)
based on randomized trial without blinding of treatment providers
201 Arabic women (aged 3554 years) living in Israel with obese body mass index and ≥ 1 components of metabolic syndrome but without diabetes,
were randomized to intensive vs. moderate lifestyle intervention for 12 months
intensive intervention included 11 individual and 11 group culturally sensitive counseling sessions with dietician and 22 group exercise sessions
moderate intervention included 3 individual and 2 culturally sensitive counseling sessions and no group exercise
comparing intensive vs. moderate lifestyle intervention at 12 months
mean weight change 2.8% vs. +0.4% (p < 0.001)
≥ 7% weight reduction in 21% vs. 5.9% (p < 0.001)
median change in triglyceride levels 4.5 mg/dL vs. +5.8 mg/dL (p = 0.02)
median change in fasting glucose 3 mg/dL vs. +1 mg/dL (p = 0.01)
Reference Arch Intern Med 2010 Jun 14;170(11):970 fulltext
weight and lifestyle program tailored to overweight or obese male soccer fans in Scotland may increase weight loss (level 2 [midlevel] evidence)
747 male fans of Scottish Premier League football (soccer) teams aged 3565 years with body mass index ≥ 28 kg/m2 were randomized to weightloss
program vs. waitlist control for 1 year
weightloss program consisting of combined advice on healthy diet with physical activity plus behavioral change techniques delivered in group
sessions by teamaffiliated community coaching staff once weekly for 12 weeks followed by telephone calls (Football Fans In Training [FFIT]
22/35
program)
all patients received weightmanagement booklet
comparing weightloss program vs. waitlist control at 1 year
mean percent weight loss 4.96% vs. 0.52% (p < 0.0001)
weightloss program associated with significantly improved selfesteem and physical healthrelated quality of life at 1 year
Reference Lancet 2014 Apr 5;383(9924):1211, editorial can be found in Lancet 2014 Apr 5;383(9924):1190
Weight Wise Program associated with weight loss in lowincome women (level 2 [midlevel] evidence)
143 lowincome women aged 4064 years with overweight or obese body mass index were randomized to evidencebased Weight Wise Program vs. control
Weight Wise Program
included 16 weekly 120minute group education sessions led by registered nurse
adapted from Diabetes Prevention Program and Dietary Approaches to Stop Hypertension (DASH) intervention from PREMIER trial
control included 2 newsletters
weight change 3.7 kg (8.1 lbs) for Weight Wise Program and +0.7 kg (+1.5 lbs) for control (p < 0.001)
involvement of family and friend support may not increase weight loss in African American adults participating in group counseling weightloss
intervention (level 2 [midlevel] evidence)
344 African American adults with BMI 2755 kg/m2 were enrolled based on 2 recruitment strata
in family support group, index person enrolled with 12 partners of own choosing
in individual group, index persons enrolled alone
persons then randomized to high social support vs. low social support groups
in high support/family group, index and partner persons attended sessions
in low support/family group, only index persons attended sessions
in high support/individual group, persons formed teams within group at sessions and were encouraged to work together in and out of sessions
in low support/individual group, persons did not form teams
group sessions included weight and activity checks, physical activity break, topic presentation, and counseling in enhancing social support
group sessions held weekly for first 6 months, biweekly for next 6 months, monthly for next year
mean weight loss overall in index persons 3.1 kg (6.8 lbs) at 6 months and 2.4 kg (5.3 lbs) at 24 months
no significant differences in weight loss in index persons at 24 months comparing
high support/family group vs. low support/family group
high support/individual group vs. low support/individual group
Reference Arch Intern Med 2009 Oct 26;169(19):1795, editorial can be found in Arch Intern Med 2009 Oct 26;169(19):1804
Technology based counseling
electronically delivered weightloss programs (for example, by telephone) that include personalized feedback from a trained professional may result in smaller
weight loss than interventions delivered facetoface (AHA/ACC Class IIa, Level A)(4)
computerbased interventions
computerbased interventions for weight loss or weight maintenance may have modest benefit compared to minimal or no intervention but may be
less effective compared to inperson interventions in overweight or obese adults (level 2 [midlevel] evidence)
based on Cochrane review with results of questionable clinical significance
systematic review of 18 randomized trials evaluating interactive computerbased interventions for weight loss or weight maintenance in 2,537
overweight or obese adults
treatment duration was 4 weeks to 30 months
14 trials evaluated computerbased interventions for weight loss
computerbased interventions associated with modest weight loss at 3 months compared to minimal or no intervention (mean difference 2.5 kg
[5.5 lbs], 95% CI 3.4 to 1.6 kg [7.5 to 3.5 lbs]) in analysis of 5 trials
addition of email and/or automated feedback to Internet program associated with modest weight loss at 34 months in multiple analyses
mean weight loss at 6 months 5.5 kg (12.1 lbs) with computerbased intervention vs. 7.6 kg (16.8 lbs) with inperson intervention (p < 0.05) in 1
trial
4 trials evaluated computerbased interventions for weight maintenance
computerbased intervention associated with modest weight loss at 12 months compared to minimal intervention (mean difference 0.78 kg
[1.72 lbs], 95% CI 1.38 to 0.17 kg [3 to 0.37 lbs]) in analysis of 3 trials with 1,004 adults, but results not significant at ≥ 18 months
computerbased intervention associated with trend toward weight gain through 18 months with significant increases at 2430 months compared
to infrequent inperson support in multiple analyses
mean weight loss at 12 months 5.7 kg (12.6 lbs) with computerbased intervention vs. 10.4 kg (22.9 lbs) with frequent inperson support (p <
0.05) in 1 trial
Reference Cochrane Database Syst Rev 2012 Aug 15;(8):CD007675
Internetbased lifestyle modification programs associated with slight weightloss benefit compared with no Internet component in overweight and
obese adults (level 2 [midlevel] evidence)
based on systematic review limited by heterogeneity
systematic review of 23 randomized trials evaluating webbased interventions (study duration range 330 months) for weight loss or maintenance in
8,697 overweight or obese adults
Internetbased lifestyle modification programs associated with slight weightloss benefit (0.68 kg [1.5 lbs]) (p = 0.03) in analysis of all trials, results
limited by significant heterogeneity
Reference Int J Obes (Lond) 2012 May;36(5):675
Internetbased behavioral intervention may increase weight loss compared to Internetbased eating and activity education in overweight or obese
adults (level 2 [midlevel] evidence)
based on randomized trial with high loss to followup
154 overweight or obese adults (mean age 53 years, 80% women) with access to personal computer and Internet were randomized to 1 of 2 Internet
based interventions for 12 weeks and followed to 6 months
behavioral intervention consisting of weekly videos teaching behavioral weightloss skills, a platform for entering selfmonitored data, and
automated feedback
eating and activity education consisting of weekly newsletters about benefits of losing weight, healthy eating, and physical activity
mean body mass index 34.9 kg/m2 and mean body weight 94.9 kg (209.2 lbs) at baseline
21% were lost to followup at 6 months, all patients included in analyses
mean weeks (out of 12) of website use was 10 with behavioral intervention vs. 9.5 with eating and activity education (not significant)
comparing behavioral intervention vs. eating and activity education at 6 months
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≥ 5% reduction in body weight in 48.1% vs. 15.6% (p < 0.001, NNT 3)
consistent findings at 3 months
Reference Diabetes Care 2015 Jan;38(1):9
Internetbased behavioral weightloss interventions may increase amount of weight loss at 6 and 24 months, and addition of inperson support may
be no more effective than remote support alone (level 2 [midlevel] evidence)
415 adults (mean age 54 years) with obese BMI and ≥ 1 cardiovascular risk factor were randomized to 1 of 3 groups
remote support behavioral weightloss support (using motivational coaching and education including diet and exercise) via telephone, email,
interactive website, and support from primary care providers
combination support remote support as above plus behavioral weightloss support via inperson (group and individual) sessions
control selfdirected weight loss (1 meeting with weightloss coach at baseline with optional meeting at 24 months) with no specific weightloss
goal or additional support
goal of both intervention groups was to reduce weight by 5% in 6 months and maintain loss for 18 months
baseline mean BMI 36.6 kg/m2 and weight 103.8 kg (229 lbs)
comparing remote support vs. control group
≥ 5% weight loss at 6 months in 52.7% vs. 14.2% (p < 0.001, NNT 3)
≥ 5% weight loss at 24 months in 38.2% vs. 18.8% (p < 0.001, NNT 6)
mean weight change from baseline 4.6 kg (10.1 lbs) vs. 0.8 kg (1.8 lbs) (p < 0.001)
consistent results for combination support vs. control group
Reference POWER trial (N Engl J Med 2011 Nov 24;365(21):1959), editorial can be found in N Engl J Med 2011 Nov 24;365(21):2030
inconsistent evidence for benefits of mobile technologybased and selfmonitoring interventions
smartphone application not associated with weight loss at 6 months in overweight adults (level 2 [midlevel] evidence)
212 overweight primary care patients ≥ 18 years old with body mass index ≥ 25 kg/m2 randomized to free smartphone application for weight loss vs.
usual care and followed for 6 months
32% of intervention group and 19% control group lost to followup
weight change 0.03 kg (0.07 lbs) for intervention group vs. + 0.27 kg (0.6 lbs) for control group (not significant)
Reference Ann Intern Med 2014 Nov 18;161(10 Suppl):S5
addition of mobile technology and telephone coaching to weightloss group meetings associated with increased weight loss for up to 12 months (level
2 [midlevel] evidence)
based on randomized trial without intentiontotreat analysis
70 adults (85.5% males) with BMI > 25 kg/m2 and ≤ 40 kg/m2 randomized to connective mobile technology system plus standard care (biweekly
weightloss groups) vs. standard care alone for 6 months and weight measured at 3month intervals for 1 year
mobile technology intervention included personal digital assistant to support selfmonitoring of diet and physical activity and biweekly coaching calls
for 6 months
73.9% completed all outcome assessments, and proportion of missing data ranged from 13% to 21.7% across postrandomization assessment periods
mobile technology system associated with
mean 3.9 kg (8.6 lbs) greater weight loss at each postbaseline assessment (no p value reported)
greater proportion of patients losing ≥ 5% of baseline weight at each postbaseline assessment (odds ratio 6.5, 95% CI 2.518.6)
Reference JAMA Intern Med 2013 Jan 28;173(2), editorial can be found in JAMA Intern Med 2013 Jan 28;173(2):111
phonedelivered intervention associated with weight loss similar to facetoface intervention in obese and overweight adults (level 2 [midlevel]
evidence)
based on randomized trial with low compliance
295 overweight or obese adults (mean age 44 years and mean body mass index 35.1 kg/m2) randomized to weightloss intervention delivered by group
telephone conference calls vs. facetoface visits at clinic for 18 months
interventions delivered once weekly for 6 months followed by gradual reduction from 7 to 18 months
weightloss program from 0 to 6 months consisted of reducing energy intake by 1,2001,500 kcal/day plus increasing physical activity to 300
minutes/week
weight maintenance program from 7 to 18 months consisted of adequate energy intake to maintain weight plus continued physical activity of 300
minutes/week
mean percent compliance with weightloss interventions 72% from 0 to 6 months and 58% from 7 to 18 months
comparing phonedelivered intervention vs. facetoface intervention
mean weight loss over first 6 months 13.4% vs. 12.3% (not significant)
≥ 15% weight loss over first 6 months in 40.7% vs. 32.7% (not significant)
≥ 15% weight loss at 18 months in 15.3% vs. 19.8% (not significant)
personal digital assistantbased selfmonitoring may not promote weight loss at 2 years compared to paper diary in overweight and obese adults
receiving behavioral intervention (level 2 [midlevel] evidence)
210 overweight or obese adults (84.8% female, 78.1% Caucasian) randomized to 1 of 3 selfmonitoring interventions and followed for 2 years
personal digital assistant (PDA) with daily tailored feedback
PDA only
paper diary
PDA software tallied consumed calories and fat grams and compared intake to goals
all patients had standard behavioral treatment for weight loss emphasizing dietary and physical activity goals, and encouragement of selfmonitoring
conducted during group sessions
≥ 60% adherence (defined as percent of days patients recorded adequate number of calories) in ≤ 72% in each group
percent weight loss 2.38% with PDA plus feedback, 1.38% with PDA only, and 1.94% with paper diary (not significant)
Reference SMART trial (Am J Prev Med 2012 Jul;43(1):20 fulltext)
daily interactive text messagebased program may be more effective for weight control than printed materials (level 2 [midlevel] evidence)
75 obese adults (mean BMI 33.2 kg/m2) randomized to text messagebased weight control intervention vs. monthly printed information about weight
control and followed for 16 weeks
text message intervention included
25 messages per day from interactive Webbased application (topics/questions addressed dietary strategies, goal setting, selfmonitoring,
nutrition and exercise education)
monthly phone call with health counselor
87% completed trial and included in analysis
comparing intervention vs. control
24/35
adjusted (for sex and age) weight loss at 4 months 2.88 kg vs. 0.91 kg (6.4 lbs vs. 2 lbs) (p = 0.02)
mean unadjusted weight loss at 4 months 4.62 kg vs. 0.17 kg (10.2 lbs vs. 0.4 lbs) (no p value reported)
Reference J Med Internet Res 2009 Jan 13;11(1):e1 fulltext
Medications
weightloss medications may be useful as adjunct to diet and physical activity for patients with
body mass index (BMI) ≥ 30 kg/m2 without concomitant obesityrelated risk factors or diseases
BMI ≥ 27 kg/m2 with concomitant obesityrelated risk factors or diseases (diabetes, hypertension, or dyslipidemia)
medications FDA approved for weight loss include
orlistat (Xenical) 120 mg 3 times daily
orlistat appears modestly effective with mean difference in weight loss 2.9 kg (6.4 lbs) (level 2 [midlevel] evidence)
halfstrength orlistat (Alli) may be modestly effective in helping mildlytomoderately overweight patients lose weight (level 2 [midlevel] evidence)
reported adverse effects which may lead to high discontinuation rates include flatus with discharge (40%), oily spotting (33%), fecal urgency (30%),
and fecal incontinence (12%)
adverse effects may be reduced by increasing fiber intake (including use of psyllium) and decreasing dietary fat
lorcaserin (Belviq) 10 mg orally twice daily
discontinue if failure to lose 5% weight after 12 weeks
addition of lorcaserin to diet and exercise counseling may increase weight loss in adults (level 2 [midlevel] evidence)
phentermine monotherapy
approved as adjunct to exercise, behavioral modification, and caloric restriction in shortterm management (a few weeks) of exogenous obesity
should not be used in combination with either selective serotonin reuptake inhibitor (SSRI) antidepressants or monoamine oxidase inhibitors (MAOIs)
phentermine plus extendedrelease topiramate combination (Qsymia) 7.5 mg/46 mg orally once daily
contraindicated in pregnancy
addition of phentermine plus topiramate to lifestyle intervention may increase weight loss in adults (level 2 [midlevel] evidence)
diethylpropion associated with weight loss in women with obesity (level 2 [midlevel] evidence)
phendimetrazine
naltrexone/bupropion extendedrelease combination (Contrave) approved for adults with obesity or overweight adults with ≥ 1 weightrelated condition such
as hypertension, diabetes mellitus type 2, or dyslipidemia (FDA News Release 2014 Sep 10)
other medications have some efficacy for weight loss, but are not FDA approved for this indication
metformin associated with a small amount of weight loss (level 2 [midlevel] evidence)
zonisamide improves weight loss in obese adults receiving diet and lifestyle counseling (level 1 [likely reliable] evidence)
bupropion may promote weight loss in overweight or obese women with bingeeating disorder (level 2 [midlevel] evidence)
addition of bupropion to zonisamide might promote weight loss in obese women (level 2 [midlevel] evidence)
topiramate may reduce weight but use limited by high rate of adverse effects (level 2 [midlevel] evidence)
combination of naltrexone and bupropion may increase weight loss (level 2 [midlevel] evidence)
topiramate and metformin each have evidence for efficacy for managing antipsychoticassociated weight gain (level 2 [midlevel] evidence)
in patients with diabetes, medications with some evidence for modest weight loss at 612 months include orlistat, canagliflozin, fluoxetine, GLP1 agonists (such as
exenatide and liraglutide), amylin agonists (including pramlintide), and bupropion (level 2 [midlevel] evidence)
most nonprescription weightloss supplements (other than orlistat) not recommended
orlistat (Alli) is only FDA approved nonprescription weightloss aid
insufficient evidence to support use of other dietary supplements for weight loss
many supplements associated with FDA warnings and alerts
imported diet pills may contain substances banned in United States
antiobesity medications withdrawn from market include
phentermine/fenfluramine (phenfen)
dexfenfluramine (Redux),
rimonabant (Acomplia, Zimulti)
sibutramine (Meridia)
metformin prevents weight gain associated with atypical antipsychotics (level 1 [likely reliable] evidence)
all medications only FDA approved for shortterm therapy but have also been used longterm (JAMA 2014 Jan 1;311(1):74 fulltext)
see Weightloss medications for obesity in adults for details
Surgery and procedures
Bariatric surgery
bariatric surgeries are part of a continuum of treatment for morbidly obese patients, not a replacement for diet and behavior modification
bariatric procedures (open or laparoscopic) include
malabsorptive procedures, including
RouxenY gastric bypass (also has a restrictive component)
biliopancreatic diversion with or without duodenal switch
restrictive procedures, including
adjustable gastric banding
vertical banded gastroplasty
sleeve gastrectomy
consider bariatric surgery for patients with
body mass index (BMI) ≥ 40 kg/m2 (Class 3 obesity) without coexisting medical problems and without excessive surgical risk (AACE/OS/ASMBS Grade A,
BEL 1)
BMI ≥ 35 kg/m2 (Class 2 obesity) and ≥ 1 of severe obesityrelated comorbidities, for weight control and improved biochemical markers of cardiovascular
disease risk (AACE/OS/ASMBS Grade A, BEL 1)
BMI ≥ 30 kg/m2 (Class 1 obesity) and ≥ 1 of severe obesityrelated comorbidities, for weight control and improved biochemical markers of cardiovascular
disease risk (AACE/OS/ASMBS Grade B, BEL 2)
BMI ≥ 30 kg/m2 (Class 1 obesity) and type 2 diabetes, for glycemic control and improved biochemical markers of cardiovascular disease
(AACE/OS/ASMBS Grade C, BEL 3)
encourage preoperative weight loss to aid surgery in patients with enlarged liver or fatty liver disease (AACE/OS/ASMBS Grade B, BEL 1) and to improve
comorbidities in selected patients (AACE/OS/ASMBS Grade D)
efficacy of bariatric surgery
comparing surgery to nonoperative management
25/35
bariatric surgery associated with reduced mortality compared to no surgery in patients with morbid obesity (level 2 [midlevel] evidence)
RouxenY gastric bypass may improve weight loss and induce remission of type 2 diabetes at 6 years more effectively than nonsurgical treatment
bariatric surgery may reduce risk of type 2 diabetes more effectively than no surgery in obese patients (level 2 [midlevel] evidence)
addition of endoscopically placed duodenaljejunal bypass sleeve implantation to dietary intervention for 6 months may promote weight loss in obese
adults with type 2 diabetes (level 2 [midlevel] evidence)
comparing surgical procedures
insufficient evidence to recommend ideal bariatric surgical procedure for severely obese patients (AACE/OS/ASMBS Grade D)
gastric bypass may be more effective than adjustable gastric banding but may have similar BMI reduction to sleeve gastrectomy (level 2 [midlevel]
evidence)
biliopancreatic diversion with duodenal switch may be more effective than RouxenY gastric bypass for weight loss in patients with morbid obesity,
but with more adverse events (level 2 [midlevel] evidence)
laparoscopic sleeve gastrectomy appears less effective than RouxenY gastric bypass for weight loss at 1 year but associated with lower reoperation or
intervention rates, and greater body mass index reduction but higher 30daymorbidity and reoperation rates than laparoscopic adjustable gastric band
patients should be evaluated and followed by multidisciplinary team for diet, physical activity, and behavioral and social support after bariatric surgery
frequency of followup depends on bariatric procedure and severity of comorbidities (AACE/OS/ASMBS Grade D)
perform initial followup at 1month post surgery for all patients
for laparoscopic adjustable gastric band, frequent band adjustments and nutritional management needed for maximal weight loss (AACE/OS/ASMBS
Grade C, BEL 3), including followup every 12 months until stabilized and every 12 months thereafter
for laparoscopic sleeve gastrectomy, followup every 36 months until stabilized and every 12 months thereafter
for RouxenY gastric bypass, followup every 3 months until stabilized and every 612 months thereafter
for biliopancreatic diversion with or without duodenal switch, followup every 3 months until stabilized and every 6 months thereafter
nutritional concerns
give micronutrient supplements for demonstrated micronutrient deficiency and consider supplementation for patients at risk for deficiency
(AACE/OS/ASMBS Grade A, BEL 2)
regular nutritional assessment should include
assessment for anemia
measurement of vitamin B12 at baseline, postoperatively, and annually in patients with surgical procedures that exclude lower part of the
stomach
measurement of 24hour urinary calcium at 6 months and annually thereafter
vitamin A measurement, and supplement if needed for patients with biliopancreatic diversion with or without duodenal switch
additional nutritional deficiencies that may develop following bariatric surgery include vitamin K, thiamine, selenium, zinc, and copper
consider bodycontouring surgery to manage excess tissue that impairs hygiene or causes discomfort or disfigurement (AACE/OS/ASMBS Grade C, BEL 3)
see Bariatric surgery for details
Liposuction
not a treatment for obesity, used instead as means of reshaping body by removing localized fat deposits (World J Gastroenterol 2006 Nov 7;12(41):6602 fulltext)
liposuction reported to reduce body mass index but not most risk factors for coronary heart disease or mediators of inflammation within 12 weeks in
adult women with obese body mass index with or without type 2 diabetes (level 3 [lacking direct] evidence)
based on case series
15 women with obese body mass index (7 with type 2 diabetes mellitus) had liposuction and were assessed at 1012 week followup
comparing before vs. after liposuction
body mass index
35.1 kg/m2 vs. 32.7 kg/m2 (p = 0.002) in 8 women with normal glucose tolerance
39.9 kg/m2 vs. 36 kg/m2 (p = 0.01) in 7 women with type 2 diabetes
waist circumference
108 cm (42.5 in) vs. 94 cm (p = 0.009) in 8 women with normal glucose tolerance
119 cm (46.9 in) vs. 107 cm (42.1) (p = 0.02) in 7 women with type 2 diabetes
serum leptin levels
31.7 ng/mL vs. 23.5 mg/mL (p = 0.05) in 8 women with normal glucose tolerance
35.7 ng/mL vs. 30.2 mg/mL (p = 0.05) in 7 women with type 2 diabetes
no significant differences in
risk factors for coronary heart disease blood pressure, plasma glucose, plasma insulin, high or lowdensity lipoprotein, or triglycerides
mediators of inflammation adiponectin, tumor necrosis factor alpha, interleikin6, or Creactive protein
Reference N Engl J Med 2004 Jun 17;350(25):2549 fulltext, editorial can be found in N Engl J Med 2004 Jun 17;350(25):2542, extensive commentary can
be found in N Engl J Med 2004 Sep 23;351(13):1354 fulltext
tumescent liposuction, subcutaneous infusion of lidocaine followed by aspiration of fat, reported to be fatal in 5 cases (N Engl J Med 1999 May 13;340(19):1471),
commentary can be found in N Engl J Med 1999 Sep 23;341(13):1000
Minnesota Health Technology Advisory Committee (HTAC) recommendations on tumescent liposuction can be found in Am Fam Physician 2003 Jan 15;67(2):427
fulltext
American Society of Plastic Surgeons (ASPS) evidencebased patient safety advisory on liposuction can be found in Plast Reconstr Surg 2009 Oct;124(4
Suppl):28S
Other procedures
intermittent vagal nerve blockade might increase weight loss in morbidly obese adults (level 2 [midlevel] evidence)
based on randomized trial with confidence interval including differences that are not clinically meaningful
239 obese patients (mean age 47 years, 85% women) randomized to active intermittent vagal nerve block device vs. sham device and followed for 1 year
vagal nerve block electrodes were implanted by standard laparoscopic techniques with general anesthesia
electrodes were connected to neuroregulator implanted intraabdominally
at baseline all patients had BMI 4045 kg/m2 or 3540 kg/m2 plus ≥ 1 obesityrelated condition
all patients received weightmanagement education
clinically meaningful effects as defined by authors
≥ 10% difference in mean excess weight loss between groups
≥ 20% excess weight loss in at least 55% of patients in vagal nerve blockade group (regardless of difference between groups)
≥ 25% excess weight loss in at least 45% of patients in vagal nerve blockade group (regardless of difference between groups)
comparing vagal nerve block device vs. sham device
mean excess weight loss 24.4% vs. 15.9% (mean difference 8.5%, 95% CI 3.113.9%)
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≥ 20% excess weight loss in 52% vs. 32% (p < 0.05, NNT 5)
≥ 25% excess weight loss in 38% vs. 23% (p < 0.05, NNT 7)
serious adverse event rate 3.7% with vagal nerve block device
Reference ReCharge trial (JAMA 2014 Sep 3;312(9):915), correction can be found in JAMA 2015 Jan 6;313(1):95, editorial can be found in JAMA 2014
Sep 3;312(9):898
Maestro Rechargeable System FDA approved for use in adults with body mass index 3545 kg/m2 and ≥ 1 other obesityrelated condition who have not responded
to weightloss program (FDA Press Release 2015 Jan 14)
addition of endoscopically placed duodenaljejunal bypass sleeve to dietary intervention may increase weight loss in obese adults with type 2 diabetes
77 obese adults (body mass index 3050 kg/m2) with type 2 diabetes were randomized to duodenaljejunal bypass sleeve implantation plus dietary
intervention for 6 months vs. dietary intervention alone and followed to 1 year
diet consisted of maximum daily energy intake of 1,200 kcal in women and 1,500 kcal in men
all doses of glucoselowering medications except metformin were reduced by 50% at time of implantation or diet initiation to avoid hypoglycemia
duodenaljejunal bypass sleeve was endoscopically placed and removed after 6 months
comparing duodenaljejunal bypass sleeve implantation vs. no implantation
mean excess weight loss at 6 months 32% vs. 16.4% (p < 0.05)
mean excess weight loss at 1 year 19.8% vs. 11.7% (p < 0.05)
mean HbA1c at 6 months 7% vs. 7.9% (p < 0.05)
mean HbA1c at 1 year 7.3% vs. 8% (not significant)
≥ 1 adverse events in 76.3% vs. 59% (no p value reported)
no significant differences in blood pressure or lipid profile at 1 year between groups
Reference Ann Surg 2014 Dec;260(6):984
Other management
Intragastric balloon
ReShape Integrated Dual Balloon System (ReShape Dual Balloon) FDA approved to treat obesity without invasive surgery in adults
indicated for weight reduction in obese adult patients with body mass index (BMI) of 3040 kg/m2
device placed endoscopically, intended for temporary use and removal after 6 months
use limited to patients with ≥ 1 obesityrelated conditions such as high blood pressure, high cholesterol, or diabetes, and who have failed at weight loss
through diet and exercise alone
efficacy based on clinical trial with 326 patients aged 2260 years with BMI 3040 kg/m2 and ≥ 1 obesityrelated health condition
patients randomized to ReShape Dual Balloon lost average 14.3 pounds (6.8% total body weight) when device removed at 6 months
control group (who had endoscopic procedure but were not given the device) lost average of 7.2 pounds (3.3% total body weight)
adverse effects from procedure may include headache, muscle pain, or nausea and (more rarely) severe allergic reaction, heart attack, esophageal tear,
infection, or breathing difficulties
adverse effects once device placed include vomiting, nausea, abdominal pain, gastric ulcers, or feelings of indigestion
contraindications include pregnancy or use in patients with previous gastrointestinal or bariatric surgery, inflammatory intestinal or bowel disease, large hiatal
hernia, symptoms of delayed gastric emptying, active Helicobacter Pylori infection, or in patients who take daily aspirin
Reference FDA Press Release 2015 Jul 28
insufficient evidence for use of intragastric balloon for obesity
based on Cochrane review
systematic review of 9 randomized and quasirandomized trials comparing intragastric balloon placement to conventional management with followup at
least 4 weeks in 395 patients
limitations included
statistical and clinical heterogeneity
moderatetohigh risk of bias in 6 of 9 trials
followup < 1 year in 6 of 9 trials
trials were limited by bias, heterogeneity, and most having duration < 1 year
no significant differences overall in weight loss
only 1 trial significantly favored intragastric balloon for weight loss
1 trial significantly favored control for weight loss
no data on quality of life, allcause mortality, or morbidity
Reference Cochrane Database Syst Rev 2007 Jan 24;(1):CD004931 (review updated 2008 Oct 3)
intragastric balloon placed endoscopically may produce weight loss at 36 months (level 2 [midlevel] evidence)
based on small randomized trial
32 adults with morbid obesity (aged 2550 years, mean BMI 43.7 kg/m2) were randomized to BioEnterics Intragastric Balloon (BIB) vs. sham procedure then
crossed over to sham vs. BIB procedure at 3 months
BIB positioned endoscopically in 1020 minutes and filled with saline 500 mL and methylene blue 10 mL, patients discharged with omeprazole and 1,000
kcal/day diet
no deaths or complications
mean BMI in patients initially treated with BIB was 43.5 at baseline, 38 at 3 months (p < 0.001) and 37.1 at 6 months
mean BMI in patients initially treated with sham procedure was 43.6 at baseline, 43.1 at 3 months (no significant difference before BIB) and 38.8 at 6 months
(after treatment with BIB)
potential clinical role suggested by study authors
temporary weight reduction to support diet therapy in morbid obesity
preoperative treatment before surgery (bariatric, orthopedic or other surgery) to reduce surgical morbidity and mortality
Reference Int J Obes (Lond) 2006 Jan;30(1):129
intragastric balloon might provide shortterm weight loss (level 3 [lacking direct] evidence)
based on systematic review of mostly case series
systematic review of 15 articles with 3,608 patients evaluating BIB for weight loss at time of balloon removal
all patients also received conventional treatment
overall mean weight loss
14.7 kg (32.4 lbs) (95% CI 12.417 kg)
12.2% of initial weight (95% CI 10%14.3%)
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32.1% of excess weight (95% CI 26.9%37.4%)
5.7 kg/m2 (95% CI 4.46.9 kg/m2)
mean weight loss in balloon group vs. placebo in metaanalysis of 2 placebocontrolled trials with 75 patients
6.7 kg (14.8) (not significant)
3.2 kg/m2 (not significant)
1.5% of initial weight (95% CI 0.9%2%) and 17.6% of excess weight (not significant)
early removal rate 4.2%
most complications mild
Reference Obes Surg 2008 Jul;18(7):841
Multicomponent interventions
Multicomponent efficacy in general populations
multicomponent weightloss programs might be effective for weight loss in adults (level 2 [midlevel] evidence)
systematic review of 12 randomized trials evaluating multicomponent weight loss programs in 4,137 overweight or obese adults
components of weightloss programs included diet, physical activity and behavioral changes
weightloss interventions and protocols varied among included trials
comparing multicomponent weightloss programs to nonactive control
multicomponent programs associated with greater weight loss at 18 months (p < 0.01) in 3 trials
no significant difference in weight loss at 18 or 24 months in 2 trials
no significant difference in weight loss comparing dietfocused multicomponent programs to active control at 18 or 36 months in 2 trials
comparing exercisefocused multicomponent programs to active control
exercisefocused multicomponent programs associated with greater weight loss at 18 months (p ≤ 0.04) in 2 trials
no significant difference in weight loss at 24 months in 1 trial
Reference Health Technol Assess 2011 Jan;15(2):1 PDF
multicomponent weightloss programs may be more effective than single or doublecomponent programs (level 2 [midlevel] evidence)
based on systematic review of trials with heterogeneity
systematic review of 24 studies evaluating various interventions for weight loss in 13,326 adults (multiethnic and minority adults in United States)
interventions included different times of exercise, nutritional advice, individual and family counseling, and medication
mean weight loss 3.5 kg (7.7 lbs)
adults participating in 3component exercise programs lost more weight compared to adults participating in single or doublecomponent programs
adults participating in interventions conducted in individual sessions lost more weight compared to adults participating in group interventions
Reference Prev Med 2008 Dec;47(6):573, editorial can be found in Prev Med 2008 Dec;47(6):583
intensive intervention including diet, medication, and counseling may reduce weight in extremely obese adults (level 2 [midlevel] evidence)
390 adults (mean age 47 years, 83% women) with BMI 4060 kg/m2 randomized to intensive primary care intervention vs. usual care and followed for 2
years
intensive primary care intervention included
3phase diet plan
phase 1 diet was liquid diet 890 kcal/day (5 shakes) plus fat 10 g daily for up to 12 weeks as tolerated
phase 2 diet was 1,200 to 1,600 kcal/day including 2 meal replacement (commercial products), 2 portioncontrolled snacks and 1 structured meal
through month 7
phase 3 diet included 1 meal replacement daily and novel dietary approaches as needed through month 24
weightloss medication (primarily sibutramine or orlistat) given during phases 2 and 3
comorbid condition treated with drugs that did not promote weight gain (venlafaxine or bupropion for depression, metformin for diabetes)
1hour group counseling sessions beginning in phase 2 held weekly for 4 weeks, then once every 2 weeks through month 7, then once per month
through month 24
usual care included instruction in use of weightmanagement website and scheduling of annual followup visits
53% completed 1year followup, 48% completed 2year followup, intentiontotreat analyses used baseline observation carried forward (BOCF) and last
observation carried forward (LOCF)
comparing mean weight loss for intensive intervention vs. usual care at 2year followup
4.9% vs. 0.2% for BOCF analysis (p < 0.001)
8.3% vs. 0 for LOCF analysis (p < 0.001)
9.7% vs. 0.4% in perprotocol analysis (p < 0.001)
comparing percent weight loss for intensive intervention vs. usual care at 2year followup in BOCF analysis
Reference LOSS trial (Arch Intern Med 2010 Jan 25;170(2):146), editorial can be found in Arch Intern Med 2010 Jan 25;170(2):121
maintenance interventions with behavioral and/or lifestyle components may promote further weight loss for up to 18 months in overweight and obese
adults (level 2 [midlevel] evidence)
systematic review of 45 randomized trials evaluating nonsurgical interventions for maintenance of weight loss in 7,788 overweight and obese adults
all patients had lost ≥ 5% of body weight within 24 months before maintenance treatment
all trials had ≥ 1 year of followup
weightloss treatment duration ranged from 2 to 12 months (median 4 months) in 42 trials
15 trials compared behavioral and/or lifestyle maintenance interventions based on diet and physical activity vs. control (usual care or no intervention)
components of interventions were not specified
behavioral and/or lifestyle interventions associated with significantly reduced weight
at 12 months (mean difference 1.56 kg [3.44 lbs]) in analysis of 15 trials, results limited by significant heterogeneity
at 18 months (mean difference 1.96 kg [4.32 lbs]) in analysis of 7 trials
no significant difference in weight at 30 months in analysis of 2 trials
Reference BMJ 2014 May 14;348:g2646 fulltext
steppedcare weightloss intervention allowing for modifications in strategies may be as effective as standard weightloss intervention but with reduced
cost in adults with body mass index (BMI) 2539 kg/m2 (level 2 [midlevel] evidence)
based on randomized trial with high loss to followup
363 adults aged 1855 years with BMI 2539 kg/m2 randomized to steppedcare weightloss intervention vs. standard behavioral weightloss intervention
28/35
(fixed program) for 18 months
all adults prescribed lowcalorie diet, increases in physical activity, and group counseling sessions ranging from weekly to monthly
steppedcare intervention allowed for modification in weightloss strategies every 3 months in response to achievement of specific weightloss goals
83% were female
28% lost to followup but included in analyses
mean weight loss at 18 months comparing steppedcare intervention vs. standard intervention
6.9% vs. 8.1% (not significant)
6.2 kg [13.6 lbs] vs. 7.6 kg [16.7 lbs] (p = 0.09)
steppedcare intervention associated with reduced cost (p < 0.001)
Reference StepUp trial (JAMA 2012 Jun 27;307(24):2617), correction can be found in JAMA 2012 Jul 11;308(2):136, editorial can be found in JAMA
2012 Jun 27;307(24):2641
repeated brief lifestyle counseling plus meal replacements or medications in primary care may increase rate of sustained weight loss at 2 years (level 2
390 adults with BMI 3050 kg/m2 (mean age 52 years) randomized to 1 of 3 groups
usual care, including quarterly primary care visits that included education about weight management
brief lifestyle counseling, including quarterly primary care visits plus brief monthly sessions with lifestyle coaches providing instruction about
behavioral weight control
enhanced brief lifestyle counseling, including same care as brief lifestyle counseling plus meal replacements or weightloss medication (orlistat or
sibutramine)
adults who received enhanced lifestyle counseling weighed less than adults who received usual care at baseline (105.4 kg [231.9 lbs] vs. 111.2 kg [244.6 lbs],
p < 0.05)
86% completed trial
mean weight loss at 2 years by intentiontotreat analysis
1.7 kg (3.7 lbs) in usual care group
2.9 kg (6.4 lbs) in brief lifestyle counseling group (not significant vs. usual care)
4.6 kg (10.1 lbs) in enhanced brief lifestyle counseling group (p = 0.003 vs. usual care, not significant vs. brief lifestyle counseling)
≥ 5% baseline weight loss at 2 years in
21.5% of usual care group
26% of brief lifestyle counseling group (not significant vs. usual care)
34.9% of enhanced brief lifestyle counseling group (p = 0.02 vs. usual care, NNT 8)
within enhanced brief lifestyle counseling group, no significant difference in mean weight loss by method of enhancement chosen (statistical comparisons
between enhanced brief lifestyle subgroups and brief lifestyle or usual care groups not reported)
3.9 kg (8.6 lbs) in 67 people who chose meal replacements
5.5 kg (12.1 lbs) in 38 people who chose sibutramine
4.6 kg (10.1 lbs) in 24 people who chose orlistat
Reference POWERUP trial (N Engl J Med 2011 Nov 24;365(21):1969 fulltext), editorial can be found in N Engl J Med 2011 Nov 24;365(21):2030,
commentary can be found in Nat Rev Cardiol 2011 Nov 29;9(1):4, Ann Intern Med 2012 Mar 20;156(6):JC311, JC3, Internist (Berl) 2012 Aug;53(8):1002
see also Diet and exercise section of Diets for weight loss and Diet plus exercise section of Physical activity for weight loss
Multicomponent efficacy in selected populations
coachled and selfdirected Diabetes Prevention Program based interventions associated with increased weight loss in overweight and obese adults with
prediabetes and/or metabolic syndrome (level 2 [midlevel] evidence)
241 overweight or obese adults (mean age 53 years, mean BMI 32 kg/m2) with prediabetes and/or metabolic syndrome randomized to usual care, coachled
group Diabetes Prevention Program (DPP) intervention, or selfdirected DPP DVD intervention for 3month intensive intervention and subsequent 12month
maintenance intervention
coachled DPP included weekly guided physical activity and food tastings
80.5% completed trial; electronic health records used to estimate missing data, but no data available for 8.3%
mean decrease in BMI from baseline
0.9 kg/m2 with usual care
2.2 kg/m2 for coachled intervention (p < 0.001 vs. usual care)
1.6 kg/m2 for selfdirected intervention (p = 0.02 vs. usual care)
percentage of patients achieving goal of losing ≥ 7% of bodyweight
14.4% with usual care
37% for coachled intervention (p = 0.003 vs. usual care)
35.9% for selfdirected intervention (p = 0.004 vs. usual care)
Reference JAMA Intern Med 2013 Jan 28;173(2):113 fulltext
in older adults
physical activity plus weight loss intervention may improve mobility and body composition compared to physical activity only or health education in
overweight or obese older adults with or at risk of cardiovascular disease (level 2 [midlevel] evidence)
based on secondary analysis of randomized trial without intentiontotreat analysis
288 overweight or obese adults (mean age 67 years, mean BMI 32.8 kg/m2) with or at risk of cardiovascular disease were randomized to 1 of 3 groups
and followed for 18 months
homebased moderate intensity exercise for > 150 minutes/week plus dietary intervention with 7%10% weight loss goal (physical activity plus
weight loss)
homebased moderate intensity exercise for > 150 minutes/week (physical activity only)
health education group sessions discussing health topics relevant to older adults (control)
86.5% completed followup, 81%88% included in analyses
mean attendance to intervention sessions was 88% in physical activity plus weight loss intervention group, 80% in physical activity only group, and
71% in control group
in original trial
physical activity plus weight loss intervention associated with improved mobility (assessed by 400meter walk time) compared to each of control
(p < 0.001) and physical activity only (p = 0.02)
no significant difference in mobility comparing physical activity only to control
physical activity plus weight loss intervention associated with improved body composition including body mass, BMI, fat mass, and lean mass
compared to each of control and physical activity only (p < 0.005 for each)
no significant differences in body composition comparing physical activity only to control
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in physical activity plus weight loss intervention group, body mass loss associated with improved cardiometabolic risk factors including diastolic blood
pressure, highdensity lipoprotein cholesterol, triglycerides, glucose, and insulin levels (p < 0.05 for each)
Reference Obesity (Silver Spring) 2014 Feb;22(2):325 fulltext
lifestyle intervention may increase weight reduction in overweight or obese postmenopausal women compared to health education, but effects may
diminish over 4 years (level 2 [midlevel] evidence)
508 postmenopausal women aged 5262 years with BMI 2539.9 kg/m2 randomized to lifestyle intervention vs. health education and followed for 4
years
lifestyle intervention was groupbased and consisted of dietary and physical activity goals, and was stopped at approximately 3 years due to lack of
funding
comparing lifestyle intervention vs. health education
≥ 10% weight loss in 42% vs. 9% at 18 months (no p value reported)
≥ 10% weight loss in 21% vs. 8% at 48 months (no p value reported)
mean total weight loss at 4 years 3.4 kg (7.5 lbs) with lifestyle intervention vs. 0.2 kg (0.4 lbs) (p < 0.05)
no significant difference at 4 years in systolic blood pressure, highdensity lipoprotein cholesterol, or triglyceride levels
modified Diabetes Prevention Program lifestyle intervention may improve weight loss at 4 months (level 2 [midlevel] evidence)
based on clusterrandomized trial with baseline differences
228 adults (mean age 71 years) with obese body mass index were randomized by senior centers to modified DPP intervention of 60minute group
sessions for 12 weeks vs. cognitive training attention control and followed for 4 months
modified DPP lifestyle intervention included goal of 7% weight loss, calorie restrictions, increased physical activity to 150 minutes/week, behavioral
strategies introduced weekly by trained lay health educators and diary selfmonitoring
baseline body mass index 37.1 kg/m2 in modified DPP and 35 kg/m2 in control group (p = 0.003)
comparing modified DPP vs. control at 4month followup
losing ≥ 5% in 38% vs. 5% (p < 0.001, NNT 3)
losing ≥ 7% in 24% vs. 3% (p = 0.001, NNT 5)
Reference Am J Prev Med 2011 Oct;41(4):385
weight loss plus multicomponent exercise intervention may improve insulin sensitivity in obese older adults with physical frailty (level 3 [lacking
direct] evidence)
based on nonclinical outcomes of small randomized trial
107 obese adults ≥ 65 years old with physical frailty randomized to diet plus multicomponent exercise intervention vs. diet alone vs. exercise alone vs.
healthy diet advice for 1 year
diet of 500750 kcal/day daily deficit with 1 g/kg of highquality protein
multicomponent exercise program included ﬂexibility, aerobic, progressive resistance, and balance exercises 3 times weekly
diet plus exercise associated with significant improvement in insulin sensitivity compared to other groups
both diet alone and diet plus exercise associated with significant improvement from baseline in visceral fat, waist circumference, triglycerides, blood
pressure, and blood glucose
Reference Int J Obes (Lond) 2014 Mar;38(3):423 fulltext
in adults with associated mental conditions
addition of brief behavioral therapy to lifestyle intervention may improve depression at 6 months in women with obesity and depression (level 2
based on secondary analysis of Be Active trial
148 women (92%) were analyzed for change in depression from baseline to 6 months and 12 months using reliable change index of Beck Depression
Inventory (BDI)
reliable change in depression defined as change in BDI score ≥ 9 points
reliable improvement in depression
in 73% with brief behavioral therapy vs. 54% with lifestyle intervention only at 6 months (p = 0.02, NNT 6)
no significant differences at 12 months
significantly associated with greater weight loss during treatment
reliable worsening in depression in < 2% of women
Reference Obesity (Silver Spring) 2013 Mar;21(3):E211 fulltext
addition of brief behavioral therapy to lifestyle intervention may not improve weight loss but may reduce depressive symptoms in women with
obesity and depression (level 2 [midlevel] evidence)
161 women (mean age 46 years) with obesity and major depressive disorder randomized to brief behavioral therapy plus lifestyle intervention vs.
lifestyle intervention alone and followed for 1 year
brief behavioral therapy consisted of promoting patient contact with positive and productive experiences to reduce depressive symptoms,
conducted during 10 weekly sessions followed by 10 weekly telephone calls
lifestyle intervention consisted of calorie goals to promote weight loss 0.51 kg (1.12.2 lbs) per week plus up to 30 minutes of moderate physical
activity 5 days weekly
lifestyle interventiononly group also received general health education
18% did not complete followup at 1 year and were excluded from analyses
mean percent weight loss 2.6% with brief behavior therapy group vs. 3.1% with lifestyle intervention alone (not significant)
brief behavior therapy associated with reduced depressive symptoms (p = 0.045)
Reference Be Active trial (Int J Obes (Lond) 2013 Nov;37(11):1427)
behavioral intervention may promote weight loss in overweight and obese adults with serious mental illness (level 2 [midlevel] evidence)
based on randomized trial with inadequate attention control
291 overweight or obese adults (mean age 45 years) with serious mental illness receiving outpatient psychiatric rehabilitation were randomized to 1 of
2 interventions for 18 months
behavioral weightloss intervention including tailored group and individual weightmanagement sessions plus group exercise sessions with
specific dietary and exercise goals
standard nutrition and physical activity information at baseline followed by optional general health classes every 3 months on topics unrelated to
weight (control)
healthy, reducedcalorie foods were available to all adults at breakfast and lunch in rehabilitation centers
at baseline, mean body mass index was 36.3 kg/m2 and mean weight was 102.7 kg (225.9 lbs)
psychiatric history of patients
58% had schizophrenia or schizoaffective disorder, 22% had bipolar disorder, and 12% had major depression
89.7% were taking antipsychotic medication and 82.8% were taking atypical antipsychotics
96% had 18month assessment and were included in analysis
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comparing behavioral intervention vs. control
≥ 5% decrease in body weight in 37.8% vs. 22.7% (p = 0.009, NNT 7)
≥ 10% decrease in body weight in 18.5% vs. 7% (p = 0.007, NNT 9)
mean weight loss 3.4 kg (7.5 lbs) vs. 0.2 kg (0.4 lbs) (p = 0.002)
Reference ACHIEVE trial (N Engl J Med 2013 Apr 25;368(17):1594 fulltext)
Acupuncture/acupressure
acupuncture associated with significant weight loss in obese patients compared with placebo and conventional treatments (level 2 [midlevel] evidence)
based on systematic review of mostly poor quality trials
systematic review of 31 randomized trials comparing acupuncture vs. placebo or comparator intervention for reduction in body weight or improvement in
obesity in 3,013 patients
compared with lifestyle control, acupuncture associated with reduction in average body weight of 1.72 kg (3.8 lbs) (p < 0.05)
compared with placebo or sham treatments, acupuncture associated with reduction in average body weight of 1.56 kg (3.4 lbs) (p < 0.05)
compared with conventional medication, acupuncture associated with
reduction in body weight (mean difference 1.9 kg [4.2 lbs], p < 0.05)
improved obesity outcomes (relative risk 1.13 kg [2.5 lbs], p < 0.05)
Reference Int J Obes (Lond) 2009 Feb;33(2):183
addition of selfapplied acupressure does not reduce weight regain at 12 months compared with social support alone in adults with prior successful weight
loss (level 2 [midlevel] evidence)
based on randomized trial
285 obese adults (mean age 56 years, 79% female) who participated in initial 6month behavioral weightloss program and lost ≥ 4.54 kg (10 lbs) randomized
to Tapas Acupressure Technique vs. no acupressure for 6 months, and followed for additional 6 months
Tapas Acupressure Technique included selfapplied light pressure to specific acupressure points plus prescribed set of mental steps to be practiced daily
all patients attended 8 social support group sessions of active weightloss maintenance over 6 months
88% completed 12month followup, but all patients randomized included in primary analysis
estimated mean weight regain at 12 months 1.72 kg (3.8 lbs) for acupressure vs. 2.96 kg (6.5 lbs) for no acupressure (p < 0.098)
Reference BMC Complement Altern Med 2012 Mar 15;12:19 fulltext
auricular acupressure with vaccaria seeds or Japanese Magnetic Pearls might slightly reduce body mass index (level 3 [lacking direct] evidence)
based on small randomized trial without direct comparison of groups as randomized
84 young adults aged 1820 years with BMI ≥ 23 kg/m2 randomized to auricular acupressure with vaccaria seeds vs. auricular acupressure with Japanese
Magnetic Pearls vs. sham tape treatment for 8 weeks
all patients received education and weekly 10minute sessions
BMI compared to baseline
decreased with auricular acupressure with vaccaria seeds by 1.2341 kg/m2 (p < 0.0001)
decreased with auricular acupressure with Japanese Magnetic Pearls by 0.6982 kg/m2 (p < 0.0001)
increased with sham tape treatment by 0.0457 kg/m2 (p < 0.0001)
Reference Am J Chin Med 2010;38(4):675
Economic incentives
groupbased financial incentive increases weight loss more than individualbased financial incentive or no financial incentive (level 2 [midlevel] evidence)
based on randomized trial with possible baseline differences
105 hospital employees aged 1870 years with body mass index 3040 kg/m2 randomized to 1 of 3 weightloss groups and weighed monthly for 24 weeks
control group
individualbased financial incentive ($100 per person per month for meeting or exceeding weightloss goals)
groupbased financial incentive ($500 per month split among employees within groups of 5 who met or exceeded weightloss goals)
possible demographic differences in control vs. individualincentive vs. groupincentive groups (no p values reported)
postcollege degree in 40% vs. 26% vs. 26%
household income ≥ $100,000/year in 49% vs. 41% vs. 34%
physical activity during week preceding trial 1,986 vs. 2,027 vs. 1,396 metabolic equivalent of task minutes
weightloss goal 0.4 kg (0.9 lbs) per week for 24 weeks
91% completed 24week weighin
mean weight loss at 24 weeks in multiple imputation regression analysis
0.5 kg (1.1 lbs) for controls
1.7 kg (3.7 lbs) for individualincentive (not significant vs. controls)
4.8 kg (10.6 lbs) for groupincentive (p < 0.001 vs. controls, p = 0.008 vs. individualincentive)
authors report consistent results in analysis adjusted for demographic factors
Reference Ann Intern Med 2013 Apr 2;158(7):505 fulltext, editorial can be found in Ann Intern Med 2013 Apr 2;158(7):560
use of economic incentives associated with increased meeting of shortterm weightloss goals (level 2 [midlevel] evidence)
based on small randomized trial
57 healthy persons aged 3070 years with BMI 3040 kg/m2 were randomized to 1 of 3 weightloss plans with weightloss goal of 1 lb (0.45 kg) per week for
16 weeks
monthly weighins (control)
lottery incentive (entrance in lottery allowed if goal met)
deposit incentive contract (deposit lost if goal not met)
5 patients did not complete trial
each incentive plan associated with greater weight loss and meeting of goals vs. control (p < 0.05 for all comparisons)
Reference JAMA 2008 Dec 10;300(22):2631 fulltext
Resting energy expenditure and brown adipose tissue activity
brown adipose tissue may increase resting energy expenditure (EE), especially through nonshivering coldinduced thermogenesis (Ann N Y Acad Sci 2013
Oct;1302:1 fulltext)
prolonged daily exposure to cold might slightly decrease body fat mass and increase coldinduced thermogenesis in adult men (level 2 [midlevel]
evidence)
based on small randomized trial without clinical outcomes
31/35
22 men with low or undetectable brown adipose tissue (BAT) activation after 2hour mild cold test (19 degrees C [66 degrees F]) were randomized to
prolonged cold exposure (17 degrees C [63 degrees F]) for 2 hours/day vs. normal lifestyle for 6 weeks
men in this trial and additional 29 men not part of this trial had mean age 24.4 years and mean body mass index 22 kg/m2
BAT activation
assessed with 18Ffluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT)
standardized uptake value (SUV) defined as amount of detected radioactivity per mL of supraclavicular and paravertebral tissue/injected
radiation dose (megabecquerels/g)
coldinduced thermogenesis (CIT) defined as difference between energy expenditure after 2hour mild cold test and energy expenditure after warm test (27
degrees C [81 degrees F])
baseline CIT 108 kcals/day in cold exposure and 102 kcals/day in normal lifestyle group (estimated from figure) (not significant)
comparing cold exposure vs. normal lifestyle
change in body fat mass from baseline 0.7 kg vs. 0.03 kg (1.54 lbs vs. 0.07 lbs) (p < 0.05)
CIT at end of trial 289 vs. 108.2 kcals/day (p < 0.05)
for 8 men in cold exposure group who had BAT activity assessed before and after 6week trial
BAT activity after 2hour mild cold test increased from 2.46 SUV at baseline to 3.89 SUV (p = 0.001)
proportion of men with BAT activity ≥ 2 SUV after 2hour mild cold test increased from 37.5% to 75% (no p value reported)
4 additional men did not have BAT activity assessed after 6week trial
Reference J Clin Invest 2013 Aug 1;123(8):3404 fulltext
interventions to increase resting energy expenditure or brown adipose tissue activity
capsinoid intake might increase resting energy expenditure in adult men with brown adipose tissue activity (level 3 [lacking direct] evidence)
18 healthy men (aged 20 to 32 years) were stratified by presence of BAT activity and then randomized to capsinoid 9 mg vs. placebo orally once, had
13 week washout, and then crossed over
resting EE assessed with indirect colorimetry before and at several time points within 2 hours of taking capsinoid or placebo
BAT activation
assessed with 18Ffluorodeoxyglucose PET/CT
SUV defined as amount of detected radioactivity per mL of supraclavicular and paravertebral tissue/injected radiation dose
(megabecquerels/g)
detectable BAT activity defined as maximum SUV > 2 after 1hour cold (19 degrees C [66 degrees F]) test
10 had detectable BAT activity
no significant difference in baseline resting EE between men with vs. without detectable BAT activity
significant increase in resting EE after capsinoid ingestion for men with detectable BAT (maximum increase of 502 kilojoules/day 1hour after
ingestion)
no significant increase in resting EE within 2 hours of
capsinoid ingestion for men without detectable BAT
placebo ingestion for men with or without detectable BAT
no significant change in skin temperature in any group
Reference Am J Clin Nutr 2012 Apr;95(4):845 fulltext
capsinoid intake might increase coldinduced thermogenesis in adult men (level 3 [lacking direct] evidence)
10 men with low or undetectable BAT activation after 2hour mild cold test (19 degrees C [66 degrees F]) were randomized to capsinoid 9 mg vs.
placebo orally once daily for 6 weeks, had 2week washout, and then crossed over for 6 weeks
men in this trial and additional 41 men not part of this trial had mean age 24.4 years and mean body mass index 22 kg/m2
capsinoids extracted from CH19 Sweet (Capsicum annuum L.)
energy expenditure assessed with indirect colorimetry
CIT defined as difference between energy expenditure after 2hour mild cold test and energy expenditure after warm test (27 degrees C [81 degrees F])
CIT was 200 kcals/day after capsinoid and 81 kcals/day after placebo (p < 0.01)
authors suggest that CIT may be proportional to BAT activation
Reference J Clin Invest 2013 Aug 1;123(8):3404 fulltext
cold acclimation associated with increased coldinduced thermogenesis and brown adipose tissue activity, but not overall resting energy expenditure
(level 3 [lacking direct] evidence)
based on prospective cohort study without clinical outcomes
17 healthy adults had cold acclimation with exposure to cold temperatures (1516 degrees C [5961 degrees F]) for 6 hours/day for 10consecutive days
and assessed for resting EE and BAT activation
resting EE assessed with indirect colorimetry
BAT activation assessed with 18Ffluorodeoxyglucose PET/CT
additional mild coldtest used to assess response to cold
comparing before vs. after cold acclimation
percentage of resting EE due to nonshivering thermogenesis during mild cold test 10.8% vs. 17.8% (p < 0.01)
volume with detectable BAT activity 665 vs. 913 cm3 (p < 0.05)
glucose mean standard uptake value in BAT 2.4 vs. 2.8 (p < 0.01)
no significant difference in overall resting EE or cold testinduced glucose uptake rate in BAT
Reference J Clin Invest 2013 Aug 1;123(8):3395 fulltext, commentary can be found in Nat Rev Endocrinol 2013 Oct;9(10):566
Followup
advise overweight and obese individuals who have lost weight to participate in longterm (≥ 1 year) comprehensive weightloss maintenance program (AHA/ACC
Class I, Level A)(4)
prescribe weightloss maintenance program which includes contact at least monthly (either facetoface or by telephone), and also includes (AHA/ACC Class I,
Level A)(4)
high levels of physical activity (200300 minutes/week)
body weight monitoring at least weekly
reducedcalorie diet
measure waist circumference at least annually in obese adults (AHA/ACC Class IIa, Level B)(4)
advise patient that even after weight loss(2)
regaining weight may occur
healthy lifestyle changes should be maintained
if weight returns, patient should reinitiate successful strategies
32/35
monthly personal contact may reduce weight regain after groupbased weightloss program (level 2 [midlevel] evidence)
1,032 overweight or obese adults aged 2883 years (63% women) with hypertension, dyslipidemia, or both who had lost ≥ 4 kg (8.8 lbs) during previous 6
month weightloss program (phase 1) were randomized to 1 of 3 groups for 30 months (phase 2)
personal contact monthly contact with interventionist (inperson for 4560 minutes every 4 months, otherwise via telephone for 515 minutes)
including status report, review of progress, and support
interactive technologybased intervention (unlimited access and encouragement to regularly log on to interactive website with same goals as personal
contact group)
selfdirected control
phase 1 intervention was groupbased behavioral intervention
trained interventionist led 20 weekly group sessions over 6 months with goals of 180 minutes per week of moderate physical activity (typically
walking), reduce caloric intake, adopt Dietary Approaches to Stop Hypertension (DASH) dietary pattern, and lose about 12 lbs per week
adults were taught to keep food and physical activity selfmonitoring records and to calculate caloric intake
mean weight loss 8.5 kg (18.7 lbs) during phase 1
mean entry weight to phase 2 was 96.7 kg (212.7 lbs)
all patients regained weight at 30 months, weight gain more pronounced in selfdirected group
mean weight gain at 30 months
5.5 kg (12.1 lbs) in selfdirected group
5.2 kg (11.4 lbs) in interactive technology group (not significant compared to selfdirected group)
4 kg (8.8 lbs) in personal contact group
mean difference vs. selfdirected group 1.5 kg (3.3 lbs) (95% CI 2.4 to 0.6 kg [5.3 to 1.3 lbs], p = 0.001)
mean difference vs. interactive technology group 1.2 kg (2.6 lbs) (95% CI 2.1 to 0.3 kg [4.6 to 0.7 lbs], p = 0.008)
weight regain lower with interactive technologybased vs. selfdirected group at 18 months (mean difference 1.1 kg [2.4 lbs], 95% CI 1.9 to 0.4 kg [4.2 to
0.9 lbs], p = 0.003) and at 24 months (mean difference 0.9 kg [2 lbs], 95% CI 1.7 to 0.02 kg [3.7 to 0.04 lbs], p = 0.04)
comparing selfdirected vs. interactive technology vs. personal contact groups
proportion of patients maintained ≥ 4 kg (8.8 lbs) weight loss from phase 1 entry 39.5% vs. 40.8% vs. 45.2% (not significant)
proportion of patients who maintained weight ≥ 5% below entry weight 33.9% vs. 35.3% vs. 42.2% (p = 0.02 for personal contact vs. selfdirected
control, NNT 12)
Reference JAMA 2008 Mar 12;299(10):1139 fulltext, commentary can be found in ACP J Club 2008 Jul;149(1):4, Evid Based Med 2008 Aug;13(4):109,
Curr Hypertens Rep 2009 Apr;11(2):83
Complications and Prognosis
Complications
even 5%15% weight loss may greatly reduce complications in obese or overweight persons(2)
obesity associated with increased risk of overall mortality
obesity associated with lifetime impact of disability and morbidity
obesity associated with increased risk for cardiovascular disease including, coronary heart disease, stroke, heart failure, atrial fibrillation, and venous
thromboembolism
obesity and lack of physical activity independently associated with increased risk for diabetes mellitus type 2
increasing body mass index (BMI) associated with increased risk of many cancers in men and women
obesity in middle age associated with increased risk for dementia
obesity associated with increased risk for gastrointestinal diseases such as gastroesophageal reflux, gallstones, and liver disease
pregnancyrelated complications include increased risks for pregnancyinduced hypertension, antepartum venous thromboembolism, labor induction, cesarean
delivery and wound infection, and fetal and neonatal mortality
numerous additional complications including
increased risk for chronic kidney disease
increased risk for kidney stones
increased risk for hot flashes
lower efficacy of oral contraceptives
lower specificity of screening mammography
increased risk for obstructive sleep apnea
obesity associated with dyspnea and asthma
orthopedic complications may include increased risk for low back pain, lumbar disk degeneration, total hip replacement, and knee osteoarthritis
infertility associated with male obesity
see Complications of obesity for details
Prognosis
Achieving weightloss goals
weight loss may peak at 6 months with weightloss interventions, and clinically meaningful weight loss relative to baseline may be maintained for up to 48
months (level 2 [midlevel] evidence)
based on metaanalysis limited to study completers
systematic review of 80 randomized trials of weightloss interventions in 26,455 persons
metaanalysis pooled results from 18,199 (69%) persons who completed at least 1 year of intervention
Metaanalysis of WeightLoss Interventions:
Intervention Mean Weight Loss*
At 6 Months At 12 Months At 24 Months At 48 Months
Advice only 0.5 kg (1.1 lbs) 0.5 kg (1.1 lbs) 0.5 kg (1.1 lbs) 0.5 kg (1.1 lbs)
Exercise only 2.4 kg (5.3 lbs) 1 kg (2.2 lbs) 1 kg (2.2 lbs) NA
Diet only 4.9 kg (10.8 lbs) 4.6 kg (10.1 lbs) 4.4 kg (9.7 lbs) 3 kg (6.6 lbs)
Exercise and diet 7.9 kg (17.4 lbs) 7.5 kg (16.5 lbs) 6 kg (13.2 lbs) 3.9 kg (8.6 lbs)
Meal replacements 8.6 kg (18.9 lbs) 6.7 kg (14.7 lbs) NA NA
17.9 kg (39.4 lbs) 10.9 kg (24 lbs) 8 kg (17.6 lbs)
33/35
Very low energy diet 5.6 kg (12.3 lbs) (36 months)
Sibutramine** 8.2 kg (18 lbs) 8.2 kg (18 lbs) 10.8 kg (23.8 lbs) NA
Orlistat 8.3 kg (18.3 lbs) 8.2 kg (18 lbs) 7.7 kg (16.9 lbs) 5.8 kg (12.8 lbs)
Abbreviation: NA, not available/applicable.
* Means estimated from graph when not provided in text.
** Sibutramine withdrawn from market.
Reference J Am Diet Assoc 2007 Oct;107(10):1755, commentary can be found in Evid Based Med 2008 Apr;13(2):41, Evid Based Nurs 2008 Apr;11(2):44
increased severity of food addiction is not associated with initial body mass index but is associated with lower reduction in weight after weightloss
program in overweight or obese adults (level 2 [midlevel] evidence)
57 overweight or obese adults (mean body mass index [BMI] 38.2 kg/m2) were assessed for food addiction and other psychological symptoms before
beginning a behavioral weightloss program
severity of food addiction (as assessed by Yale Food Addiction Scale)
not associated with preprogram BMI or body satisfaction in correlation analysis
associated with lower reduction of weight after 7 weeks in weightloss program in correlation analysis
associated with increased psychological symptoms such as depression, emotional eating, binge eating, antifat attitudes, internalized weight bias, body
shame, and low selfefficacy of eating in correlation analyses
Reference Appetite 2013 Jan;60(1):103
Obesity paradox
obesity paradox being overweight or obese but fit according to metabolic and cardiorespiratory measures may not be associated with increased mortality
being overweight or obese may be associated with improved prognosis among persons with chronic conditions including
cardiovascular conditions such as hypertension, coronary heart disease, atrial fibrillation, or peripheral arterial disease
other chronic conditions such as kidney disease, HIV infection, arthritis, and some lung diseases
reasons for paradox not known, but might include
younger age or greater metabolic reserve among patients classified as obese or overweight at presentation
unintended weight loss or cachexia in patients classified as normal weight
Reference Nat Rev Endocrinol 2015 Jan;11(1):55
obesity in patients with normal cardiovascular fitness may not be associated with increased risk of mortality (level 2 [midlevel] evidence)
review of 10 studies with 93,006 persons assessing mortality rates stratified by studyspecific cardiorespiratory fitness and BMI weight classification
compared with normalweight fit persons
poor cardiorespiratory fitness associated with increased risk of mortality among obese, overweight, or normalweight persons
in obese persons, hazard ratio (HR) 2.46 (95% CI 1.923.14) in analysis of 8 studies
in overweight persons, HR 2.14 (95% CI 1.772.58) in analysis of 8 studies
in normalweight persons, HR 2.42 (95% CI 1.962.99) in analysis of 10 studies
normal cardiorespiratory fitness may not be associated with increased risk of mortality among obese or overweight persons
in obese persons, HR 1.21 (95% CI 0.951.52) in analysis of 8 studies (results limited by significant heterogeneity)
in overweight persons, HR 1.13 (95% CI 11.27) in analysis of 8 studies (results limited by significant heterogeneity)
Reference Prog Cardiovasc Dis 2014 JanFeb;56(4):382
see Physical activity for cardiovascular disease prevention for additional information
unclear association between being obese or overweight and mortality among patients with acute coronary syndrome
based on systematic review of observational studies with significant risk of bias
review of 26 studies with 218,532 patients with acute coronary syndrome that assessed patients' BMI and mortality rates
overweight or obese patients were younger in 20 of 26 studies
compared to patients with normal BMI
reduced mortality in patients classified as
overweight (relative risk [RR] 0.7, 95% CI 0.640.76) in analysis of 26 studies
obese (RR 0.6, 95% CI 0.530.68) in analysis of 26 studies
severely obese (RR 0.7, 95% CI0.580.86) in analysis of 10 studies
increased mortality in patients with low BMI (RR 1.74, 95% CI 1.472.05) in analysis of 9 studies
among patients ≥ 65 years old, mortality was higher among patients classified as overweight or obese than in patients with normal BMI
Reference Eur J Epidemiol 2014 Nov;29(11):801 fulltext
being overweight or obese but not severely obese may be associated with decreased risk of mortality in patients hospitalized in intensive care (level 2
systematic review of 23 prospective cohort studies evaluating associations between BMI categories and mortality in critically ill adults in intensive care
settings
risk of mortality compared to reference BMI 18.524.9 kg/m2
decreased in overweight patients (BMI 2529.9 kg/m2, pooled odds ratio [OR] 0.91, 95% CI 0.840.98) in 14 studies
decreased in obese patients (BMI 3039.9 kg/m2, pooled OR 0.82, 95% CI 0.680.98) in 8 studies
not significantly different in severely obese patients (BMI > 40 kg/m2, pooled OR 0.94, 95% CI 0.821.07) in 10 studies
length of hospital stay evaluated in 11 studies
significantly longer in obese or severely obese patients in 6 studies
no significant differences in 5 studies
obesity may not increase risk of mortality in patients in intensive care facilities but may increase duration of mechanical ventilation and length of stay in
intensive care (level 2 [midlevel] evidence)
based on systematic review
34/35
systematic review of 14 observational studies comparing outcomes in 62,045 obese (BMI ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) critically ill patients
in intensive care settings
comparing obese vs. nonobese patients in metaanalyses with significant heterogeneity
mortality 11.4% vs. 12.6% (not significant)
mean duration of mechanical ventilation 1.48 days longer for obese patients (95% CI 0.072.89) in analysis of 6 studies with 7,387 patients
mean length of stay in intensive care unit 1.08 days longer for obese patients (95% CI 0.271.88) in analysis of 13 studies with 61,651 patients
Reference Crit Care Med 2008 Jan;36(1):151, editorial can be found in Crit Care Med 2008 Jan;36(1):369
overweight and obesity not associated with increased risk of mortality in adults with type 2 diabetes (level 2 [midlevel] evidence)
10,568 adults (median age 63 years) with type 2 diabetes followed for median 10.6 years
compared to normal weight, overweight and obesity not associated with increased risk of allcause mortality in adults with type 2 diabetes
Reference Ann Intern Med 2015 May 5;162(9):610, summary for patients can be found in Ann Intern Med 2015 May 5;162(9)
Effect of obesity on quality of life
increased BMI associated with poorer healthrelated quality of life
based on study of 1,168 male outpatients (mean age 54.7 years) in United States Veterans' Affairs medical center
increasing BMI associated with lower scores for
bodily pain subscale (BMI > 25 kg/m2)
physical functioning and physical component subscales (BMI > 35 kg/m2)
rolephysical and vitality subscales (BMI > 40 kg/m2)
Reference Obes Res 2002 Oct;10(10):1057
see also Complications of obesity
weightloss interventions appear to have little effect on healthrelated quality of life (level 2 [midlevel] evidence)
based on systematic review of 34 randomized trials of weightloss interventions lasting 6208 weeks
only 9 trials showed improvements in healthrelated quality of life
trials limited by multiple methodologic flaws
Reference J Clin Epidemiol 2005 Jun;58(6):568
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