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Overweight and Obesity

Overweight and Obesity. Harvey Hsu M.D. July 9, 2007. Introduction. Obesity is a multifactorial chronic disease Involves social, behavioral, cultural, physiological, metabolic and genetic factors. Second leading cause of preventable death in the United States

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Overweight and Obesity

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  1. Overweight and Obesity Harvey Hsu M.D. July 9, 2007

  2. Introduction • Obesity is a multifactorial chronic disease • Involves social, behavioral, cultural, physiological, metabolic and genetic factors. • Second leading cause of preventable death in the United States • More evident in some minority groups, those with lower incomes, and less education

  3. Overweight and Obese • Substantially raises risk of morbidity from hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and some cancers. • Social stigmatization and discrimination

  4. Body Mass Index (BMI) • BMI = weight (kg)/ height (m2) or 704.5 x lb/in2 • Overweight is defined as a BMI of 25 to 29.9 kg/m2 • Obesity is a BMI of ³ 30 kg/m2 • Normal is a BMI 24.9 kg/m2 to 18.5 kg/m2 • Underweight is <18.5 kg/m2

  5. Obesity • Obesity class 1 BMI 30.0-34.9 • Obesity class 2 BMI 35.0- 39.9 • Obesity class 3 BMI >= 40 • Waist circumference • Men > 102 cm ( > 40 in) • Women > 88 cm ( > 35 in)

  6. Body Mass Index • Lindsay Lohanis 5’6” and 112 lb BMI 18.1 • Jennifer Lopez is 5’6” and 118 lb BMI 19 • Amare Stoudemire is 6’10” and 245lb BMI 25.6 • George Bush is 6’0” and 190 lb BMI 25.8 • Arnold Schwarzenegger 6’2” and 257. BMI 33 • Competition wt 235 BMI 30.2

  7. Body Mass Index • Walter Hudson (worlds fattest man) was 1400 lbs , height 5’ 11” ? BMI 198 • Robert Wadlow (worlds tallest man) was 8’11” and 440 lb BMI 27.4

  8. NHANES • 65.7 percent of U.S. Adults are overweight or obese. (2001-2002) • 33 percent are at a healthy weight • Total 65.1 % overweigh or obese, 30.4% were obese, and 4.9% were extremely obese. (1999-2002)

  9. NHANES

  10. Hypertension • Age adjusted prevalence of high blood pressure increases progressively with higher levels of BMI • Each kg of weight loss decreases systolic BP by 2.5mm and diastolic 1.7 mm/Hg

  11. Dyslipidemia • Overweight and obesity are associated with increased cholesterol levels. • Increased triglycerides • Decreased HDL • Increased LDL

  12. Diabetes Mellitus • The increased risk of diabetes as weight increases has been shown by prospective studies • Relative risk of diabetes increases by approximately 25% for each additional unit of BMI over 22 kg/m2

  13. Coronary Heart Disease • Observational studies have shown that overweight, obesity, and excess abdominal fat are directly related to cardiovascular risk factors, including high levels of total cholesterol, LDL-cholesterol, triglycerides, blood pressure, fibrinogen and insulin [86] , and low levels of HDL- cholesterol

  14. Congestive heart failure • Overweight and obesity have been identified as important and independent risk factors for congestive heart failure (CHF) in a number of studies, including the Framingham Heart Study

  15. Stroke • Overweight may be associated with ischemic stroke • Recent prospective studies demonstrate that the risk of stroke shows a graded increase as BMI rises • ischemic stroke risk is 75 percent higher in women with BMI > 27, and 137 percent higher in women with a BMI > 32, compared with women having a BMI < 21

  16. Gallstones • Risk of gallstones increases with adult weight • Risk of either gallstones or cholecystectomy is as high as 20 per 1,000 women per year when BMI is above 40, compared with 3 per 1,000 among women with BMI < 24

  17. Osteoarthritis • Association with increased weight and knee osteoarthritis is stronger in women. • Every kilogram increase in weight increased the risk of developing osteoarthritis by 9 to 13%

  18. Sleep Apnea • Obesity, particularly upper body obesity, is a risk factor for sleep apnea and has been shown to be related to its severity • Most people with sleep apnea have a BMI>30 • Large neck girth is predictive

  19. Cancer • Colon cancer • Breast Cancer • Endometrial cancer • Gallbladder cancer • overweight and obesity in the United States couldaccount for 14 percent of all deaths from cancer in men and20 percent of those in women

  20. Relative to the normal weight category (BMI 18.5 to 25), obesity (BMI >30) was associated with 111 909 excess deaths (95% confidence interval [CI], 53 754- 170 064) and underweight with 33 746 excess deaths (95% CI, 15 726-51 766). Overweight was not associated with excess mortality (-86 094 deaths; 95% CI, -161 223 to -10 966). JAMA. 2005;293:1861-1867 www.jama.com

  21. Natural laws of Prehistoric Times • Eat when hungry • Eat food high in fat • Sleep near food supply • Conserve energy

  22. Treatment • Diet • Exercise • Pharmacotherapy • Surgery

  23. Diet • 3500 kcal is equivalent to 1 pound • Multiply your body weight times 13. • Add to that the number of calories you typically burn off during exercise each day. • Subtract 2% of that total for each decade after the age of 30. • The result is your daily caloric need.

  24. Diet • Calculate total required calories • Have patient record all meals • Behavior therapy • VLCDs produce greater initial weight loss than LCDs. However, the long-term (> 1 year) weight loss is not different from that of the LCD

  25. Exercise • One additional pound of fat burns 2 kcal/day • One additional pound of muscle burns 75 kcal/d • Maintains lean body mass and metabolism • The combination of a reduced calorie diet and increased physical activity produces greater weight loss than diet alone or physical activity alone

  26. Pharmacotherapy • Dexfenfluramine/fenfluramine • Phentermine • Sibutramine (Meridia) • Orlistat (Xenical)

  27. Dexfenfluramine/fenfluramine • Serotonin reuptake inhibitor/serotonin releaser • Adverse Effects: • Valvular heart disease • Primary pulmonary hypertension • Neurotoxicity

  28. Phentermine • A sympathomimetic amine • CNS stimulation • Elevation of blood pressure

  29. Sibutramine (Meridia) • Norepinephrine, dopamine, and serotinin reuptake inhibitor • Adverse Effect- increase in heart rate and blood pressure, BP 1-3 mm/Hg HR 4-5 b/min • Use in BMI>30 • Or in BMI >27 with risk factors

  30. Orlistat (Xenical) • Inhibits pancreatic lipase, decreases fat absorption • Adverse effects • Decrease in absorption of fat soluble viatmins • Soft stools and anal leakage • Possible link to breast cancer

  31. Orlistat (alli)

  32. Other • Ephedrine, caffeine, fluoxetine, wellbutrin have been used for weight loss but not FDA approved. • Zonisamide (Topamax) • Recombinant Variant of Ciliary Neurotrophic Factor (CNTF) • SR141716 (Rimonabant)

  33. Antiobesity drugs in pipeline • Rimonabant(Acomplia) Cannabinoid receptor antagonist • Axokine – Nerve growth factor agonist • AC137/Pramlintide –Delays gastric emptying • AOD9604 – Increases lipolysis, decreases lipogenesis, and raises resting energy expenditure • ADP356 – Selective 5-HT2C receptor antagonist • GT 389-255 – Gastrointestinal lipase inhibitor conjugated to fat-binding polymer

  34. Zonisamide (Topamax) • 16 week randomized, double-blind, placebo-controlled trial with optional single-blind extension for 16 more weeks • At 16 weeks: 5.9kg (6.0%) vs 0.4kg (1.0%) • At 36 weeks: 9.2kg (9.4%) vs 1.5kg (1.8%)

  35. Recombinant Variant of Ciliary Neurotrophic Factor (CNTF) • 12 week double-blind, randomized, parallel group, dose-ranging, multicenter clinical trial • Placebo: 0.1kg • rhvCNTF 0.3 mcg/kg: -1.5kg • rhvCNTF 1.0 mcg/kg: -4.1kg • rhvCNTF 2.0 mcg/kg: -3.4kg

  36. Acomplia (rimonabant) 62.5 percent of patients treated for the full two years with the higher dose of Acomplia lost more than 5 percent of their body weight compared to 36.7 percent of those on the low dose of Acomplia and 33.2 percent of patients in the control group. 32.8 percent of patients treated for the full two years with the higher dose of Acomplia lost more than 10 percent of their body weight compared to 20 percent of patients on the low dose of Acomplia and 16.4 percent of patients in the control group

  37. · Placebo AXOKINE 0.5 mcg/kg      1.0 mcg/kg Intent-to-Treat Analysis ** 2.5 lbsn=52 5.2 lbsn=52* p= .08 6.5 lbsn=53* p< 0.01 Completer Analysis *** 2.6 lbsn=48 (92%) 5.6 lbsn=47 (90%)* p= .07 7.0 lbsn= 47 (89%)* p< 0.01 Axotine

  38. Surgery • Gastrointestinal surgery (gastric restriction [vertical gastric banding] or gastric bypass [Roux-en Y]) can result in substantial weight loss, and therefore is an available weight loss option for well-informed and motivated patients with a BMI >40 or 35, who have comorbid conditions and acceptable operative risks

  39. Gastric Bypass Laparoscopic Adjustable Gastric Band

  40. Gastric Bypass Vertical Banded Gastroplasty

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