ObesityThe Perils of Portliness
AIMGP Clinic
14 Jan 2003
Prepared by Damon Scales, M.D.
Updated by Tim Cook (8/1/3)
References
Periodic Health Examination, 1999: Detection, prevention, and treatment of obesity. CMAJ 1999;160:513-25
Executive Summary of the Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Arch Intern Med 1998;158:1855-1867
Yanovsky et al. Obesity. NEJM 2002;346:591-602Willett et al. Guidelines for Healthy Weight. NEJM
1999;341:427-434
References Cont’d
K.Fontaine, et al, Years of Life Lost Due to Obesity, JAMA, 2003; 289 : 187-193
A.Peeters, et al, Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis, Ann Intern Med. 2003; 138: 24-32
Health & Drug Alerts, Obesity drug sibutramine (Meridia), CMAJ, 2002; 166(10) 1307
References
Lau,D. Call for action: preventing and managing the expansive and expensive obesity epidemic. CMAJ 1999;160:503-505
Birmingham,CL et al.How much should Canadians eat?. CMAJ 2002;166(6):767-770
Bray,G. Drug Therapy of Obesity. UpToDate 2002. Davidson et al. Weight Control and Risk Factor Reduction in
Obese Subjects Treated for 2 Years with Orlistat. JAMA 1999;281:235-241
Sjostrom et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998;352:167-172
The Case
34 year old man referred by family physician for opinion regarding obesity managementHe states that he has been overweight for most of
his lifeHe lives by himself, and eats mostly pre-made
mealsHe works as a long-haul truck driver, and
exercises infrequently
The Case
PMHappendectomyinguinal hernia repair
Family HistoryFather - MI age 54Older brother - DM 2Both of his parents have always been obese
No medications
The Case
Exam reveals:moderate obesity
Weight 250 lbs (113.6 kg)Height 5’ 10” (177.8 cm)BMI 35.9
BP 130/76 HR 72 bpm RR 12Cardiac Exam
JVP 3 cmnormal S1, S2, no murmurs
Remainder of examination normal
Questions:
How would you counsel this patient?What other conditions are associated with
obesity?Would you advise him to lose weight? How?
NEJM, Aug. 7, 1997
Why do people gain weight?
Beyond the scope of this seminar, but first law of thermodynamics applies…“The amount of stored energy equals the difference
between energy intake and work”Amount of triglyceride in adipose tissue is the cumulative
sum over time of the difference between energy (food) intake and energy expenditure
Current availability of highly palatable, calorically dense foods and a sedentary lifestyle promote weight gain
from NEJM, Aug. 7, 1997
Complex Interactions which Determine Relationship Between Energy Intake and Expenditure
Nature versus Nurture
Studies in twins suggest as much as 80% of variance in BMI is attributable to genetic factorsCertain single gene disorders may result in marked obesity
(Prader-Willi, Bardet-Biedl, Alstrom, etc.)
But, potent environmental influences on adiposity... inverse relation between obesity and social classsecular trend toward increasing obesity
Diagnosis and Definitions
Body Mass Index = weight (kg)
height (m)2
Greater reproducibility than skinfold thickness indicesCannot distinguish between increased weight due to
adiposity or fluid retention
Body circumference indices identify adults with a central (android) pattern of obesity who are at
higher risk of obesity-related problems, independent of BMI Use of these indices limited by lack of established normal reference
ranges
Definitions
Much controversy in literature regarding definitions of overweight and obesity
Canadian Periodic Health Examination, 1999 update:obesity defined as BMI > 27morbid obesity defined as BMI > 35
American Medical Association, 1998 Expert Panel on Obesityoverweight defined as BMI between 25 and 29.9obesity defined as BMI > 30
Scope of the ProblemObesity Pandemic! 10-20% of all people in “rich
countries” BMI > 27 (obesity):
35% of men, 27 % of women (Canada)
BMI > 35 (morbid obesity)2% of men, 4% of women (Canada)
Total direct cost of obesity estimated > $1.8 billion (~2.4% of total direct medical costs)CMAJ Feb. 23, 1999. The Cost of Obesity in Canada
Scope of the Problem Associated Conditions
HypertensionDiabetes MellitusHyperlipidemiaCoronary Artery
DiseaseObstructive Sleep
Apnea
MalignanciesBreastUterusProstateColon
Psychological Disordersdepressionanorexia nervosabulimia
The Evidence for Mortality
Annals Int Med 2003 ArticleFramingham Data
Signif decreases in Life Expectancy40 y.o. Non-smoker Smoker
Overweight female 3.3 y 7.2 y
Overweight male 3.1 y 6.7 y
Obese female 7.1 y 13.3 y
Obese male 5.8 y 13.7 y
BMI at 30-49 y predicted mortality at ages 50-69 EVEN after adjustment for BMI at 50 -69 y
JAMA 2003 Article
Data from US Life Tables and NHANES I-III (Nat’l Health & Nutrition Exam. Survey)
Derive YLL (Yrs Life Lost) for ages 18-85 based on BMI
Marked race and sex differencesFor any degree of overweight, younger adults had
greater YLL than older20-30 yo w.m. BMI>45 = 13 YLL (22%20-30 yo w.f. BMI>45 = 8 YLL
Prevention
Several studies of community-based interventionsseminarsmailed educational packagesmass media participation
Several methodological problems, but no significant weight reductions achieved
TherapyAim of weight reduction should be to
decrease morbidity rather than meet cosmetic standards of thinness
Set reasonable short-term goalsRecognize that any lifestyle alterations will
need to be continued indefinitely if lower body weight is to be maintained2/3 of persons who lose weight will regain it within one
yearalmost all persons who lose weight will regain it within
5 years
Goals
Initial goal - reduce body weight by 10% within ~ 6 monthsFor BMI 27 - 35: deficits of ~ 300-500 kcal/d will lead to
weight loss of ~ 0.23 - 0.45 kg/wk (10% in 6 mos)For BMI > 35: deficits of ~ 500-1000 kcal/d will lead to
weight loss of ~ 0.45 - 0.9 kg/wk (10% in 6 mos)
Further weight loss can be attempted (if indicated) after this goal is achieved
Dietary Therapy
Weight reducing diets that consist of drastically altered proportions of nutrients may be dangerous and no more effective than more well-balanced diets
Dietary TherapyTwo main strategies have included
low-calorie diet (800 - 1500 kcal/d)very-low-calorie diet (<800 kcal/d)
8 RCT’s/6prospective studies:consistent pattern of initial weight loss (mean -2.6 kg)
followed by gradual weight gain
the diet should be consistent with the NCEP Step I or Step II diet
Reducing fat alone will not produce
weight loss unless total energy intake
is also reduced
Dietary Therapy
Reduction of weight most effective during period of supervision, but across studies a pattern of gradual weight regain occurred in unsupervised period
Underestimation of caloric intake well-documented in obesity… portion size is main problem
REFER to a Dietician! They are much better at this intervention than we are...
Exercise
Increases caloric expenditure and also may promote dietary compliance
intermittent exercise (high intensity followed by low intensity) results in greater reduction in weight and fat than continuous exercise of low-medium intensity with the same caloric expenditure
Exercise
Most weight loss occurs because of decreased intake, and exercise will not lead to substantially greater weight loss over 6 months
BUT… Sustained physical activity is most helpful in the prevention of weight regain
Intensity of exercise should be increased graduallyExample: start walking 30 min/day, 3 days per week and
build to 45 minutes of more intense walking at least 5 days per week
Behavior Modification Therapy
Involves analyzing the meaning of eating for a person and the circumstances in which a person tends to eatMay be helpfulMay not be
5 RCT’s, 4 prospective cohort studiesmodest weight reduction (1 - 5kg) with gradual weight regain
during follow-up period
Back to the Case
He returns 3 months laterHe lost 2 kg in the first month, but has since
regained 1 kgHe is now exercising 3 times per week (walks 30
minutes)
He asks you, “Look Doc, Can’t I just take a pill to lose weight? Or should I just have that stomach-stapling operation?”What do you tell him?
Anorectic Drug Therapy
Dexfenfluramine and fenfluramineserotonin-reuptake inhibitorseffective as appetite suppressantsresult in weight loss when used for 6 months to 1 year
THESE DRUGS WORK!! But...
Withdrawn from market after association noted with use of these drugs and
valvular heart diseaseprimary pulmonary hypertension
Sympathomimetic DrugsIncrease brain concentrations of catecholamines
leading to decreased appetite or increased expenditureExamples: phenteramine, mazindolphenylpropanolamine removed from OTC market by FDA after
recent demonstration of risk of hemorrhagic strokeunsuitable for obese persons with evidence of cardiovascular
disease
Few small studies involving these agents:Modest benefit (-3kg in small RCT involving Mazindol)
in short term; long term effectiveness (after 1 year of F/U) has not been studied
Sympathomimetic DrugsThese drugs have only modest benefit in
promoting weight loss, and should be used with extreme caution in patients with cardiac disease, hypertension, or history of strokeAMA recommendation: consider these agents as
adjunctive to dietary therapy for:patients with BMI > 30patients with BMI > 27 and any of
CAD, HTN, DM, Sleep apnea
CMA Periodic Health Exam:insufficient evidence to recommend in favor of or against
Sibutramine
Approved in Canada late 2001(but taken off market in Italy d/t 2 CV deaths)Drug with both catecholaminergic and serotonergic
agonist effects ---> enhances satiety, incr metab ratemodestly enhances weight loss and can help facilitate
weight loss maintenance increases in blood pressure and heart rate with useContraindicated in patients with CAD, HTN, CHF, stroke
2 small RCTs (1 year F/U) - suggest modest weight loss (mean 5.2 kg in one trial) but high drop-out rates (up to 44%)
Sibutramine
Risk:benefit & Cost:benefit profile must be discussed before prescribing
Check HR, BP before Rx, q2/52 X 3/12 then q1-3/12
Consider D/C ing Rx IF HR incr 10 beats/min or BP incr 10 mm Hg (either syst or diast) in 2 consecutive visits.
Orlistat
Only drug available that alters fat metabolisminhibits pancreatic lipases resulting in incomplete
breakdown of ingested fatfecal fat excretion increased (peaks at ~30% of
ingested fat)
Orlistat
Lancet 1998 - RCT, 743 patients, 2 yearsat 1 year: -10.3 kg in orlistat group vs. -6.1 kg at year 2: regain of weight when orlistat stopped (though less
regain than in placebo group)63% completed trial
Side effects: (orlistat vs placebo) fatty stool - 31% vs. 5% increased defecation 20% vs. 7% “oily spotting” - 18% vs. 1% fecal urgency - 10% vs. 3% fecal incontinence 7% vs. 0% flatus with discharge 7% vs. 0%
Orlistat JAMA 1999 - RCT of 1187 patients
at 1 year: -8.8 kg (orlistat) vs - 5.8kgagain, weight regain when orlistat stopped45% completed 2 year trialReduction in LDL also seen (mean -0.22 mmol)adverse event rate and profile similar to previous Lancet
trial
Bottom Line: Orlistat may result in weight loss, but…weight regain may occur once it is stoppedbothersome GI effects are likely to be unacceptable to
many patients
Surgery
Bariatric or weight-reduction surgerygastric bypass (complete gastric partitioning with
anastomosis of proximal gastric segment to a jejunal loop)
gastroplasty (partial gastric partitioning at the proximal gastric segment with placement of a gastric outlet stoma of fixed diameter)
Both methods intended to create an upper gastric pouch that reduces gastric luminal capacity and causes early satiety
Surgical Interventions
4 RCTs, 1 prospective studylong-term success in sustaining initial weight
reduction which occurred in first 3-6 monthsmagnitude of weight loss greater than that
observed with dietary/drug treatmentsPost-operative mortality low (1 death in 707
patients)Perioperative morbidity < 5%
Surgical Interventions
Reserved for patientsin whom efforts at medical therapy have failedwho are suffering from complications of extreme
obesity
AMA recommendation:May consider bariatric surgery in patients
with clinically severe obesity (BMI > 40)with BMI > 35 with comorbid conditions
Summary
Weight loss for obese patients is desirableto help control diseases worsened by obesity
(diabetes, coronary artery disease, etc.)to help decrease the likelihood of developing the
associated diseases
SummaryThe initial strategy should include
dietary therapy with a low-calorie dietexercise (especially to help prevent weight regain)
Pharmacologic therapy provides only modest benefit, and often has unacceptable side effects Dexfenfluramine and fenfluramine are no longer available because of risk
of severe adverse events
Sympathomimetic drugs are only marginally effective and should not be recommended to most patients
Orlistat provides modest incremental benefit in promoting weight loss, but often has intolerable GI side effects
Bariatric surgery may be effective for some patients, but should be reserved for patients with severe obesity (BMI > 40) in whom other strategies fail
SummaryCMA Periodic Health Exam:
a) community-based obesity prevention methods are ineffective
b) obesity treatment methods are ineffective over the long term (beyond 2 years) exceptin small proportion of people who receive dietary or
surgical treatmentsin patients with selected obesity-related diseases
weight loss may reduce need for drug therapy for the related diseases
c) insufficient evidence to recommend in favor of our against inclusion of BMI as part of periodic health exam
Back to the Case
You decide with your patient to embark on a trial of orlistatInitially, he finds the flatulence he develops to be
quite bothersome (no oily stools!), but over time learns that this can be minimized by avoiding foods which are high in fat-content
At the next 3 month follow-up appointment he has been successful at maintaining his low-calorie diet and exercise regimen, and he reports with great pride that he has lost a further 3 kg!
The End