Disease X in 1985 No Data <10% 10%–14%

Disease X in 1986 No Data <10% 10%–14%

Disease X in 1987 No Data <10% 10%–14%

Disease X in 1988 No Data <10% 10%–14%

Disease X in 1989 No Data <10% 10%–14%

Disease X in 1990 No Data <10% 10%–14%

Disease X in 1991 No Data <10% 10%–14% 15%–19%

Disease X in 1992 No Data <10% 10%–14% 15%–19%

Disease X in 1993 No Data <10% 10%–14% 15%–19%

Disease X in 1994 No Data <10% 10%–14% 15%–19%

Disease X in 1995 No Data <10% 10%–14% 15%–19%

Disease X in 1996 No Data <10% 10%–14% 15%–19%

Disease X in 1997 No Data <10% 10%–14 15%–19% ≥20%

Disease X in 1998 No Data <10% 10%–14 15%–19% ≥20%

Disease X in 1999 No Data <10% 10%–14 15%–19% ≥20%

Disease X in 2000 No Data <10% 10%–14 15%–19% ≥20%

Disease X in 2001 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Disease X in 2002 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Disease X in 2003 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Disease X in 2004 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Disease X in 2005 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Source: Behavioral Risk Factor Surveillance System, CDC. Alcohol Medical Scholars Program Obesity* Among U.S. Adults, 2006 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

23Alcohol Medical Scholars Program OBESITY: AN EXPANDING EPIDEMIC

24Alcohol Medical Scholars Program Obesity Major public health concern Related to high calorie intake Influenced by –Physiology –Environment –Genes

25Alcohol Medical Scholars Program Covered Topics Obesity –Definition and epidemiology –Comorbid illness –Mechanism of disease –Treatment

26Alcohol Medical Scholars Program Obesity Body mass index (BMI)=kg/m 2 BMIWeight in lbs for 5’8” Normal Overweight Obese≥30.0≥ 197 Class I Class II Class III≥40.0≥262

27Alcohol Medical Scholars Program Who is obese? 66% in United States overweight or obese –32% obese –5% extreme obesity Mexican American 76% Non-Hispanic Black 76% Non-Hispanic White 64%

28Alcohol Medical Scholars Program Covered Topics Obesity –Definition and epidemiology –Comorbid illness –Mechanism of disease –Treatment

29Alcohol Medical Scholars Program So what? 300,000 obesity-related deaths/year in US 5x risk for diabetes 5x risk for gallbladder disease More depression and bipolar disorder More deaths from heart disease

30Alcohol Medical Scholars Program Covered Topics Obesity –Definition and epidemiology –Comorbid illness –Mechanism of disease –Treatment

31Alcohol Medical Scholars Program Mechanisms of Obesity Environment –Types of food available –Increased portion size –Sedentary lifestyle

32Alcohol Medical Scholars Program Mechanisms of Obesity 50% of risk is genetic –Concordance: 60% dizygotic 75% monozygotic –Adoptee weight more like biological parents –Gene mutations Leptin Proopiomelanocortin (POMC) –Bred in or out of mice

33Alcohol Medical Scholars Program Mechanisms of Obesity: Feeding Dopamine with food Opioids will feeding Leptin Ghrelin

34Alcohol Medical Scholars Program Stress Eating and Opioids Stress consumption of comfort food Opiates sugar intake POMC β-endorphin α-MSH ACTH RewardStress Feeding

35 Alcohol Medical Scholars Program Extrinsic factors food-related cue & availability Emotional factors Stress, boredom Intrinsic factors Leptin Ghrelin Dopamine Hypothalamus Signals that Control Feeding

36Alcohol Medical Scholars Program Dopamine and Reward Dopamine critical to reward –Pleasure dopamine Drugs Sex Food –Too much pleasure dopamine Drugs Food

37Alcohol Medical Scholars Program p < Dopamine and Obesity Control Obese Dopamine D2 receptor imaging BMI Dopamine Receptor Concentration Obese o Control p = 0.3 Wang et al, Lancet 2001

38Alcohol Medical Scholars Program Food Craving When do we crave? –Chronic stress –Food deprivation What do we crave? –Sweets –Carbohydrates

39Alcohol Medical Scholars Program Carbohydrates (mmmm…) Dopamine Opiates Serotonin Alcohol is carbohydrate rich –Is food –Is drug

40Alcohol Medical Scholars Program From Chocolate to Morphine Sugar preferring rats –Increased cocaine –Increased morphine –Increased alcohol

41Alcohol Medical Scholars Program Drug Withdrawal and Sweets Increased sweets consumption after –Smoking cessation –Alcohol abstinence –Opiate withdrawal –Cocaine withdrawal No impairment in taste

42Alcohol Medical Scholars Program Weight Loss and Alcohol Calorie restricted body wants calories –Prefers carbohydrates –Calorie deprived rats drink alcohol Surgically treated obesity –Decreased calorie intake –Overcome size restriction by liquid calories Standard drink = 100 calories

43Alcohol Medical Scholars Program Covered Topics Obesity –Definition and epidemiology –Comorbid illness –Mechanism of disease –Treatment

44Alcohol Medical Scholars Program Weight Loss Strategies Improve health Address behavioral change Address neurobiological change?

45Alcohol Medical Scholars Program Treatment: Surgery Roux-en-Y –Restrict stomach size / decrease absorption –25% in body weight Vertical banded gastroplasty –Restrict stomach size –15% in body weight

46Alcohol Medical Scholars Program Treatment: Behavioral Brief Intervention –Medical consequences –Impact of dietary change –Impact of exercise Diet and exercise 5% in body weight

47Alcohol Medical Scholars Program Treatment: Behavioral Overeaters Anonymous –Get peer network –Change attitudes Cognitive behavioral therapy –Help patient change view of eating –Help change behavior to weight loss –Help recognize and avoid risk situations

48Alcohol Medical Scholars Program Treatment: Behavioral Motivational interviewing –Emphasize change –Discuss resistance –Encourage acceptable change Behavioral therapy alone 5% weight

49Alcohol Medical Scholars Program Treatment: Medications Decrease appetite / increase metabolism –Sibutramine: inhibits monoamine reuptake –Rimonabant: cannabinoid receptor antagonist Decrease absorption –Orlistat: fat absorption in gut Decrease appetite –Naltrexone?: opioid antagonist Medications 5% in body weight

50Alcohol Medical Scholars Program Conclusions Obesity morbidity and mortality Overlapping neuropathways with addiction Treatments –Surgical –Behavioral –Pharmacological

51Alcohol Medical Scholars Program Future Studies Needed Is eating behavior replaced? Elucidate common neuropathways Elucidate common genetics

52Alcohol Medical Scholars Program In the Meantime Screen for overweight and obesity (BMI) Counsel about healthy eating Treat or refer to treatment –Behavioral –Pharmacological –Surgical

53Alcohol Medical Scholars Program