Update in Obesity: the 10 Most Interesting Studies in DGIM Grand Rounds January 26, 2010

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Update in Obesity: the 10 Most Interesting Studies in 2009 DGIM Grand Rounds January 26, 2010 Adam Gilden Tsai, MD, MSCE Assistant Professor of Medicine

Acknowlegements Conflicts of Interest: none Slides Frank Greenway, MD Dan Bessesen, MD

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

Obesity Rates Are Stabilizing Ogden CL, et al. NCHS data brief no 1. Hyattsville, MD: National Center for Health Statistics. 2007.

Obesity and Metabolic Risk NHANES 1999-2004 N = 5440 aged 20 and older Metabolically abnormal (0-1 versus 2 or more) BP ( 130/85) TG( 150) hscrp( 0.1 mg/l) Fasting glucose ( 100) HOMA (homeostasis model assessment) HDL (<40 men, <50 women) Wildman RP. Arch Intern Med 2008:168(15):1617-1624

Obesity and Metabolic Risk A = Non-Hispanic whites; B = Non-Hispanic blacks; C = Mexican-Americans

Take Home Patients with BMI 25 kg/m 2 should undergo routine testing of fasting glucose (or A1c) and lipids But not everybody needs treatment for their weight

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

Obesity and Sleep Deprivation 10 healthy, overweight volunteers Two 14-day study periods, 3 months apart Randomized to 5.5 hours or 8.5 hours of sleep Actual sleep: 5.25 and 7.5 hours Calorie intake of 90% of requirement Balanced deficit diet Darukhanavala A. Obesity 2009:17(S2):S48.

Obesity and Sleep Deprivation Weight losses: 3.0 vs 2.9 kg; NS Lean tissue loss: 75% vs 49% (p < 0.01) Significantly increased hunger by VAS in sleep-restricted group (0.64 cm; p < 0.01) Darukhanavala A. Obesity 2009:17(S2):S48.

Obesity and Television Viewing TV viewing is associated with obesity and with weight gain Lower metabolic rate than any other sedentary activity The average American watches 4 hours of TV per day (#3 after work and sleep)

Obesity and Television Viewing Randomized trial, n = 36 3 week observation period to estimate TV watching Average was 4.8/5.3 hours per day Randomized to control condition versus block on TV after 50% of baseline viewing time

Obesity and Television Viewing Otten JJ. Arch Intern Med 2010;169(22):2109-2115

Take Home *8-5-3-2-1-almost none 8 (HOURS OF SLEEP) 5 (fruits and veggies per day) 3 servings of dairy (low-fat) 2 (MAX HOURS SCREEN TIME) 1 (hours or more of physical activity) Almost none (sugar-sweetened beverages) *Christy Boling, MD, MHS (UT Southwestern/Houston VA)

Obesity and Secondary Prevention Health and Retirement Survey (RAND) Individuals < 75 yo, BMI 25 kg/m 2 Regression analysis controlled for: Age Sex Race/ethnicity Educational status baseline BMI and health status Marital status Weight status of spouse Smoking status Employment status Health insurance status Income Keenan PS. Arch Intern Med. 2009;169(3):237-242

Obesity and Secondary Prevention New dx of heart disease or diabetes Gain of 0.04 BMI units over 2 years for entire sample Decrease of 0.35 BMI units for 1 dx (2.5 lbs for a 220 lb, 5 foot 8 person) Decrease of 0.64 BMI units for 2 dx (4 lbs for a 220 lb, 5 foot 8 inch person) Keenan PS. Arch Intern Med. 2009;169(3):237-242

Take Home Use new diagnoses as an opportunity to counsel patients about their weight Use metabolic syndrome in the same way

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

How important is macronutrient content? N = 811 individuals followed for 2 years Individual and group counseling Carbohydrate Fat Protein 65% 55% 45% 35% 20% 20% 40% 40% 15% 25% 15% 25%

Macronutrient Content of Diet Did Not Affect Weight Loss at 2 Years Sacks FM. N Engl J Med 2009;360:859-73.

Take Home Caloric restriction and self-monitoring are more important than macronutrient content for the average patient

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

Qnexa Topiramate and Phentermine Topiramate stimulates GABA and is approved for migraines and epilepsy Phentermine releases norepinephrine and is approved for short-term (3 months) obesity treatment Controlled release combination, taken daily, 4- week titration period in trials T/P: High-dose = 92/15mg, Mid-dose = 46/7.5mg and Low-dose = 23/3.37mg

Qnexa Phase III Conquer Trial

Adverse Events in Qnexa Trial Qnexa Topir Phent Placebo Alt.Taste 16% 2% 2% 2% Paresth. 38% 22% 4% 2% Ur. Freq. 14% 2% 2% 6% Headach 10% 8% 14% 2% Memory 8% 4% 0% 12% Insomnia 2% 4% 2% 12%

Take Home New drugs are coming Contrave (Buproprion-Naltrexone) Empatic (Buproprion-Zonisamide) Lorcaserin (5HT2 agonist) Tesofensine (norepinephrine, dopamine, serotonin reuptake inhibitor) Likely to be combination agents Cost will be prohibitive for many patients

Sibutramine + Counseling DiGenio AG. Ann Intern Med. 2009;150:255-262.

Sibutramine + Counseling DiGenio AG. Ann Intern Med. 2009;150:255-262.

Take Home Weight loss medication and high-intensity weight loss counseling are additive Caveat: recent FDA alert about increased risk of CV events for patients taking Meridia in the SCOUT (Sibutramine Cardiovascular OUtcome Trial) in Europe

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

Bariatric Surgery Getting Safer 4776 patients undergoing first-time surgery Mean (±SD) age 44.5 ±11.5 years; 21% men Median BMI 46.5 82.1% of the patients had at least one condition, 53.9% had two or more, and 26.5% had three or more Hypertension (55.1%), obstructive sleep apnea (48.9%), diabetes (33.2%), asthma (23.1%); CAD (4.4%), venous edema with ulcerations (4.0%), a history of deep-vein thrombosis or venous thromboembolism (3.5%), dependence on supplemental oxygen (3.5%), congestive heart failure (2.2%), an inability to walk 200 ft (1.8%), and pulmonary hypertension (1.2%). LABS (Longitudinal Assessment of Bariatric Surgery) Consortium. NEJM 2009:361:445-54.

Bariatric Surgery Getting Safer Surgery Type Bypass 3412 (71.4%), of which 87.2% laparoscopic Laparoscopic banding 1198 patients (25.1%) Other 166 patients (3.5%) not included for outcomes Outcomes: 30-day rate of death for banding or bypass = 0.3% 0% of banding patients 0.2% of laparoscopic bypass 2.1% of open bypass No difference in mortality after adjustment for patient or center characteristics banding 4.3% of patients had at least one major adverse outcome: death; venous thromboembolism; percutaneous, endoscopic, or operative reintervention; failure to be discharged from the hospital) LABS (Longitudinal Assessment of Bariatric Surgery) Consortium. NEJM 2009:361:445-54.

Bariatric Surgery Getting Safer LABS (Longitudinal Assessment of Bariatric Surgery) Consortium. NEJM 2009:361:445-54.

Take Home Refer patients that meet criteria for surgery BMI 40 kg/m 2 or 35 kg/m 2 with comorbidity Patients with diabetes

Outline Epidemiology Obesity Prevention Diet Pharmacotherapy Surgery Public Policy

A Natural Experiment Does calorie labeling reduce calorie intake? 11 fast food chains in NYC Subway posted point-of purchase calorie information prior to NYC law on labeling N = 7,318 (receipts analyed) Bassett MT. Am J Public Health. 2008;98:1457 1459.

Public Policy Calorie Posting Average = 827 calories consumed Subway customers more likely to see calorie information (32% vs 4%) To consume fewer calories if they saw calorie information (714 vs 766 calories) Subway customers less likely To purchase high calorie meals ( 1000 calories): 17% vs. 23% Calorie posting at Subway described as not prominent

Take Home Aggressive public policy measures are likely to be needed to make changes at the population level Not all will agree Elbel B. Health Affairs. 2009;28(6):w1110 21

SUMMARY 8-5-3-2-1-almost none Caloric restriction, not macronutrient content Watch for new medications Combine medication and lifestyle modification Refer for surgery in selected patients Policy change

THANK YOU Questions? Comments?

Public Policy Calorie intake from beverages increased by 222 calories per person from 1965 to 2002, mostly from sweetened drinks 1 Calorie intake from sweetened beverages increased from 70 to 190 kcal per person from 1977 to 2001 2 42 Starbucks and 73 Dunkin Donuts stores during the spring of 2007 1,127 beverage purchases at Starbucks and 1,830 at Dunkin Donuts Duffey KJ, Popkin BM. Obesity 2007;15(11):2739-47. Nielsen SJ, Popkin BM. Am J Prev Med 2004;27(3):205-10. Huang C et al. Prev Chronic Dis 2009;6(4):1-8.

Calories from Coffee Purchases Huang C et al. Prev Chronic Dis 2009;6(4):1-8.

Obesity Treatment in Primary Care Tsai AG, Wadden TA. J Gen Intern Med 2009:24:1073-1079.

Obesity Treatment in Primary Care Tsai AG, Wadden TA. J Gen Intern Med 2009:24:1073-1079.

USPSTF recs The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen all adult patients for obesity and offer intensive counseling and behavioral interventions to promote sustained weight loss for obese adults. This is a grade B recommendation.

USPSTF recs It is advisable to refer obese patients to programs that offer intensive counseling and behavioral interventions for optimal weight loss High intensity = >1 person-to-person session per month for the first 3 months Medium intensity = monthly Low intensity intervention = < monthly