Obesity The Perils of Portliness

1. ObesityThe Perils of Portliness AIMGP Clinic 14 Jan 2003 Prepared by Damon Scales, M.D. Updated by Tim Cook (8/1/3)

2. 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;346:591-602 • Willett et al. Guidelines for Healthy Weight. NEJM 1999;341:427-434

3. 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

4. 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

5. The Case • 34 year old man referred by family physician for opinion regarding obesity management • He states that he has been overweight for most of his life • He lives by himself, and eats mostly pre-made meals • He works as a long-haul truck driver, and exercises infrequently

6. The Case • PMH • appendectomy • inguinal hernia repair • Family History • Father - MI age 54 • Older brother - DM 2 • Both of his parents have always been obese • No medications

7. 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 12 • Cardiac Exam • JVP 3 cm • normal S1, S2, no murmurs • Remainder of examination normal

8. Questions: • How would you counsel this patient? • What other conditions are associated with obesity? • Would you advise him to lose weight? How?

9. 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 NEJM, Aug. 7, 1997

10. Complex Interactions which Determine Relationship Between Energy Intake and Expenditure from NEJM, Aug. 7, 1997

11. Nature versus Nurture • Studies in twins suggest as much as 80% of variance in BMI is attributable to genetic factors • Certain 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 class • secular trend toward increasing obesity

12. Diagnosis and Definitions • Body Mass Index = weight (kg) height (m)2 • Greater reproducibility than skinfold thickness indices • Cannot 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

13. Definitions • Much controversy in literature regarding definitions of overweight and obesity • Canadian Periodic Health Examination, 1999 update: • obesity defined as BMI > 27 • morbid obesity defined as BMI > 35 • American Medical Association, 1998 Expert Panel on Obesity • overweight defined as BMI between 25 and 29.9 • obesity defined as BMI > 30

14. Scope of the Problem • Obesity 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

15. Hypertension Diabetes Mellitus Hyperlipidemia Coronary Artery Disease Obstructive Sleep Apnea Malignancies Breast Uterus Prostate Colon Psychological Disorders depression anorexia nervosa bulimia Scope of the ProblemAssociated Conditions

16. Annals Int Med 2003 Article Framingham Data Signif decreases in Life Expectancy 40 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 The Evidence for Mortality

17. 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 differences • For any degree of overweight, younger adults had greater YLL than older • 20-30 yo w.m. BMI>45 = 13 YLL (22% • 20-30 yo w.f. BMI>45 = 8 YLL

18. Prevention • Several studies of community-based interventions • seminars • mailed educational packages • mass media participation • Several methodological problems, but no significant weight reductions achieved

19. Therapy • Aim of weight reduction should be to decrease morbidity rather than meet cosmetic standards of thinness • Set reasonable short-term goals • Recognize that any lifestyle alterations will need to be continued indefinitely if lower body weight is to be maintained • 2/3 of persons who lose weight will regain it within one year • almost all persons who lose weight will regain it within 5 years

20. Goals • Initial goal - reduce body weight by 10% within ~ 6 months • For 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

21. 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

22. Dietary Therapy • Two 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

23. 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...

24. 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

25. 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 gradually • Example: start walking 30 min/day, 3 days per week and build to 45 minutes of more intense walking at least 5 days per week

26. Behavior Modification Therapy • Involves analyzing the meaning of eating for a person and the circumstances in which a person tends to eat • May be helpful • May not be • 5 RCT’s, 4 prospective cohort studies • modest weight reduction (1 - 5kg) with gradual weight regain during follow-up period

27. Back to the Case • He returns 3 months later • He lost 2 kg in the first month, but has since regained 1 kg • He 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?

28. Anorectic Drug Therapy • Dexfenfluramine and fenfluramine • serotonin-reuptake inhibitors • effective as appetite suppressants • result 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 disease • primary pulmonary hypertension

29. Sympathomimetic Drugs • Increase brain concentrations of catecholamines leading to decreased appetite or increased expenditure • Examples: phenteramine, mazindol • phenylpropanolamine removed from OTC market by FDA after recent demonstration of risk of hemorrhagic stroke • unsuitable 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

30. Sympathomimetic Drugs • These 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 stroke • AMA recommendation: consider these agents as adjunctive to dietary therapy for: • patients with BMI > 30 • patients with BMI > 27 and any of • CAD, HTN, DM, Sleep apnea • CMA Periodic Health Exam: • insufficient evidence to recommend in favor of or against

31. 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 rate • modestly enhances weight loss and can help facilitate weight loss maintenance • increases in blood pressure and heart rate with use • Contraindicated 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%)

32. 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.

33. Orlistat • Only drug available that alters fat metabolism • inhibits pancreatic lipases resulting in incomplete breakdown of ingested fat • fecal fat excretion increased (peaks at ~30% of ingested fat)

34. Orlistat • Lancet 1998 - RCT, 743 patients, 2 years • at 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%

35. Orlistat • JAMA 1999 - RCT of 1187 patients • at 1 year: -8.8 kg (orlistat) vs - 5.8kg • again, weight regain when orlistat stopped • 45% completed 2 year trial • Reduction 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 stopped • bothersome GI effects are likely to be unacceptable to many patients

36. Surgery • Bariatric or weight-reduction surgery • gastric 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

37. Surgical Interventions • 4 RCTs, 1 prospective study • long-term success in sustaining initial weight reduction which occurred in first 3-6 months • magnitude of weight loss greater than that observed with dietary/drug treatments • Post-operative mortality low (1 death in 707 patients) • Perioperative morbidity < 5%

38. Surgical Interventions • Reserved for patients • in whom efforts at medical therapy have failed • who 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

39. Summary • Weight loss for obese patients is desirable • to help control diseases worsened by obesity (diabetes, coronary artery disease, etc.) • to help decrease the likelihood of developing the associated diseases

40. Summary • The initial strategy should include • dietary therapy with a low-calorie diet • exercise (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 drugsare 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

41. Summary • CMA Periodic Health Exam: • a) community-based obesity prevention methods are ineffective • b) obesity treatment methods are ineffective over the long term (beyond 2 years) except • in small proportion of people who receive dietary or surgical treatments • in 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

42. Back to the Case • You decide with your patient to embark on a trial of orlistat • Initially, 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!

43. The End