1. OBESITY AND PREVENTION Nutrition 500 WEIGHT LOSS RECIDIVISM 1-5-06 Division of Metabolism, Endocrinology and Nutrition John Brunzell, MD

2. OBESITY AND PREVENTION Nutrition 500 WEIGHT LOSS RECIDIVISM 1-5-06 Division of Metabolism, Endocrinology and Nutrition John Brunzell, MD

3. Build and Blood Pressure Study 1959 Build Study 1979 American Cancer Society Study 1979 Manson, JAMA 1987;257:353 Mortality Ratio % of Average Weight Men 2.5 2.0 1.5 1.0 0.5 0 8090100110120130140150160 Mortality Increases With Body Weight 48 yo

4. Medical Complications of Obesity Phlebitis venous stasis Coronary heart disease Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Gall bladder disease Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Gout Stroke Diabetes Osteoarthritis Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Hypertension Dyslipidemia Cataracts Skin Infections Idiopathic intracranial hypertension Pancreatitis NAASO

5. NEJM 1999 p427 Women Men Middle aged

6. Medical Complications of “Central” Obesity Coronary heart disease Gynecologic abnormalities polycystic ovarian syndrome Gout Stroke Diabetes Nonalcoholic fatty liver disease steatosis steatohepatitis Hypertension Dyslipidemia Modified from NAASO

7. Current and projected obesity prevalence rates from 1960 to 2025 Kopelman. Nature 404, 635 - 643 (2000)

8. SMOKING AND BMI: NHANES 88-91 Flegal et al. NEJM 1995, p1165 KG 8.5 5.3 3.8 1.5 3.0 1.8 3

11. In conditions of plenty, body weight is 60-80% genetically determined D. Cummings

13. Monozygotic Twins

14. Dizygotic Twins

15. Adopted Children’s Weight Correlates With Weight of Their Biological, Not Adoptive, Parents Stunkard et al, NEJM 1986;314:193 BMI of Parents (kg/m 2 ) Thin Median Overweight Obese Biological Parents Adoptive Parents 27 21 26 25 24 23 22 Weight Category of Children Fathers Mothers

16. Genetic Leptin Deficiency Causes Obesity in ob/ob mice

17. Farooqi et al, JCI 110:1093, 2002 Leptin Deficiency also Causes Obesity in Humans Obesity in Humans

18. Weight Regain After Behavior Modification Diet Program: 16 studies 0 20 40 60 80 100 012345 Duration of Follow-Up (years) % Weight Regain Safer. So. Med. J. 84:1470, 1991

20. Diabetes Prevention Program Regaining weight, final results not in

29. 24 Hour Energy Expenditure

31. BEFORE AND AFTER WEIGHT LOSS

32. 24 Hour Non-resting Energy Expenditure

34. Adam Drewnowski and reduced obese individuals “Sweet and Fat Tooth” Physiol Behavior 1985, 35:617-622

35. Usual weight Weight loss Weight gain “Adipostatic” Body Weight Regulation Counter regulation R. Schwartz, 1982

36. Usual weight Weight loss Weight gain “Adipostatic” Body Weight Regulation Counter regulation R. Schwartz 1982

37. Body weight is regulated within a narrow, individualized range.

38. body fat stores leptin/insulin Adiposity Negative Feedback - energy balance

39. body fat stores Food intake Energy expenditure - Circulating signals Adiposity Negative Feedback

41. Copyright ©2005 American Society for Clinical Investigation Rosenbaum, M. et al. J. Clin. Invest. 2005;115:3579-3586 Schematic of protocol

42. Copyright ©2005 American Society for Clinical Investigation Rosenbaum, M. et al. J. Clin. Invest. 2005;115:3579-3586 Effects of weight loss and leptin administration on circulating leptin concentrations

43. Copyright ©2005 American Society for Clinical Investigation Rosenbaum, M. et al. J. Clin. Invest. 2005;115:3579-3586 Energy expenditure and skeletal muscle

44. Body Weight Ballpark: 5-10% Volitional Control Body Weight (lbs) Time 0 100 200 300 0 100 200 300

45. 20 year old male 170 lb. 60 year old male 210 lb. 1 lb. per year = 3500 kcal/365 days...or… ~10 kcal/day

48. Prevalence of Overweight Children and Adolescents in the United States Is Increasing 0 5 10 15 1963–701971–741976–801988–941999 Prevalence of Overweight (%) Troiano. Arch Pediatr Adol Med 1995;149:1085 NHANES 1999: www.cdc.gov/nchs/products/pubs/pubd/hestats/overweight99.htm Children, 6–11 y Adolescents, 12–17 y

49. OBESITY AND PREVENTION Nutrition 500 Dietary fat and fructose? Sedentary lifestyle?

52. Venus of Willendorf (24,000 BCE)

53. Miss America: An Undernourished Role Model? Rubinstein and Caballero JAMA. 2000;283:1569-1569

57. MORTALITY IN MEN 60-69 YEARS OLD 1979

58. The Metabolic Syndrome Hypertension Type 2 Diabetes Dyslipidemia Visceral Obesity Increased PAI-1 InsulinResistance  Free Fatty Acids Atherosclerosis

59. Oligogenic Metabolic Disorders Metabolic Syndrome Familial Combined Hyperlipidemia Type 2 Diabetes

60. PREMATURE CORONARY DISEASE Metabolic Syndrome Familial Combined Hyperlipidemia Type 2 Diabetes 15-20%20-30%