3/11/2019. Debate: A Conversation on Weight Management and Health at Every Size. Defining Obesity. Obesity: In the top three global social burdens

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1 Foundational Concepts Debate: A Conversation on Weight Management and Health at Every Size Robert F. Kushner, MD, MS Professor of Medicine Northwestern University Feinberg School of Medicine Director, Center for Lifestyle Medicine Northwestern Medicine Chicago, IL Defining Obesity Obesity: In the top three global social burdens Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health A crude population measure of obesity is the body mass index (BMI) GDP, $ trillion Selected global social burdens Global GDP % Historical trend Smoking Armed violence, war, and terrorism Obesity Alcoholism Illiteracy Climate change Outdoor air pollution Drug use.7 1. Road accidents.7 1. Workplace risks.4.6 Household air pollution.4.5 Child and maternal undernutrition.3.5 Unsafe sex.3.4 Poor water and sanitation.1.1 McKinsey Global Institute. Overcoming obesity: An initial economic crisis. November 214. Available at: systems andservices/our insights/how the world could better fight obesity (Accessed 5 May 217) Obesity is associated with multiple comorbidities Metabolic, Mechanical and Mental Global DALYs associated with high BMI 199 and 215 Sleep Apnoea Depression Metabolic Cardiovascular diseases Stroke Anxiety Dyslipidaemia Mechanical Hypertension Asthma Coronary artery disease Coronary heart failure Mental NAFLD Pulmonary embolism Gallstones Chronic back pain Cancers* Infertility Type 2 diabetes Prediabetes Physical functioning Incontinence Thrombosi Arthrosis s Gout NAFLD, non-alcoholic fatty liver disease *Including breast, colorectal, endometrial, esophageal, kidney, ovarian, pancreatic and prostate Adapted from Sharma AM. Obes Rev. 21;11:88-9; Guh et al. BMC Public Health 29;9:88; Luppino et al. Arch Gen Psychiatry 21;67:22 9; Simon et al. Arch Gen Psychiatry 26;63:824 3; Church et al. Gastroenterology 26;13:223 3; Li et al. Prev Med 21;51:18 23; Hosler. Prev Chronic Dis 29;6:A48 Disability adjusted life years in 199 Disability adjusted life years in 215 Disability adjusted life years (in millions) % 2.1%.2% 25.6% 2.9% 4.2% 35.4%.3% % 4.1% 3.3% 6.4% 18.% 3.4%.4%.6% 5.8% 11.5%.8%.8% 2.1%.3% 3.1% 2.8% 4.7%.3% Body mass index Body mass index Musculoskeletal disorders Cardiovascular diseases Cancers Chronic kidney disease Diabetes Mellitus DALYs, disability adjusted life years Disability adjusted life years (in millions) % 18.7% 2.8% 33.7% GBD 215 Obesity Collaborators. N Engl J Med 217;377:

2 Association of Weight Gain from Early (18 21 years) to Middle (55 years) Adulthood with Risk of Developing Major Chronic Disease* *T2DM, hypertension, CVD, obesity related cancer, cholelithiasis, osteoarthritis, cataract, death Association of Weight Gain from Early (18 21 years) to Middle (55 years) Adulthood with Risk of Developing Major Chronic Disease Nurses Health Study & Health Professionals Follow up Study Mean weight gain of 12.6 kg over 37 years among women and 9.7 kg over 34 years among men Those who gained more weight were more likely to be physically inactive, to be never smokers, to have unhealthy dietary habits, and to have a higher prevalence of chronic diseases at the age of 55 years. No self reported history of chronic disease No cognitive decline No physical limitations Zheng Y et al, JAMA 217;318: Zheng Y et al, JAMA 217;318: Obesity increases lifetime risk of CVD morbidity Obesity is associated with impaired physical function Middle aged men Middle aged women BMI (kg/m 2 ) 3 to <35 35 to <4 4 Follow up, years 3.2 Million person years of follow up from 1964 to 215 All participants were free of clinical CVD at baseline CVD, cardiovascular disease Follow up, years Change in SF 36 domain score Female Male 2 Physical functioning compared with normal weight (BMI 18.5 to <25) SF 36, Short Form 36 Khan SS et al. JAMA Cardiol 218 Apr 1;3(4): Hopman et al. Qual Life Res 27;16: Lipotoxicity Products of fat tissue The link between pathophysiology of obesity and associated comorbid conditions Excess adiposity leads to major risk factors and common chronic diseases Adiposity Inflammation Adiponectin Hypertension TNFα Angiotensinogen Arthritis TNF ß Dyslipidemia IL6 FFA Insulin Asthma Adipose prostaglandins EGF Cancer Adipsin Resistin Stroke, Heart attack Leptin PVD Tissue LIPOTOXICITY PAI 1 Type 2 diabetes Estrogen Thrombosis TNFα =tumor necrosis factor alpha; EGF = epidermal growth factor; PAI 1 = plasminogen activator inhibitor 1; IL6 = interleukin 6 Adipokine synthesis Adipose tissue macrophages and other inflammatory cells Pro inflammatory cytokines Impaired insulin signalling and insulin resistance Insulin T2D Lipid production Activity of the sympathetic nervous system Hydrolysis of triglycerides Release of fatty acids Renal compression Lipotoxicity Dyslipidaemia Systemic and pulmonary NAFLD hypertension NASH Cirrhosis CHD CHF Stroke CKD Activity of the reninangiotensin aldosterone Mechanical stress system Pharyngeal soft Mechanical Intra abdominal tissue load on joints pressure OSA Osteoarthritis GERD Barrett s oesophagus Oesophageal adenocarcinoma Reviewed in Kershaw EE, et al. J Clin Endocrinol Metab. 24;89: ; Hajer GR et al. European Heart Journal. 28;29: CHD, coronary heart disease; CHF, coronary heart failure; CKD, chronic kidney disease; GERD, gastroesophageal reflux disease; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic stereohepatitis; OSA, obstructive sleep apnea; T2D, type 2 diabetes. Heymsfield SB, Wadden TA. NEJM 217;376:

3 How do we Define Health Outcomes and Evidence based Measures? Weight loss as a primary treatment to improve co morbid conditions and quality of life (QOL) in patients who at increased risk Rely on randomized, controlled, prospective trials; and observational studies Weight loss improves obesity related comorbidities AACE Obesity Guidelines Benefits of 5 1% weight loss Reduction in risk of type 2 diabetes 1 Reduction in CV mortality 2 blood lipid profile 3 blood pressure 4 severity of obstructive sleep aponea 5,6 health related quality of life 7,8 1. Knowler et al. N Engl J Med 22;346:393 43; 2. Li et al. Lancet Diabetes Endocrinol 214;2:474 8; 3. Datillo et al. Am J Clin Nutr 1992;56:32 8; 4. Wing et al. Diabetes Care 211;34:1481 6; 5. Foster et al. Arch Intern Med 29;169: ; 6. Kuna et al. Sleep 213;36:641 9; 7. Warkentin et al. Obes Rev 214;15:169 82; 8. Wright et al. J Health Psychol 213;18: US Preventive Services Task Force (USPSTF) Recommendation Statements AHA/ACC/TOS Obesity Guidelines Recommendation Screen all adults for obesity Clinicians should offer or refer patients with a BMI of 3 kg/m 2 or higher to intensive, multicomponent behavioral interventions 1 Clinicians offer or refer adults with a BMI of 3 kg/m 2 or higher to intensive, multicomponent behavioral interventions 2 Grade B = The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. BMI, body mass index B B Recommendation Class Grading Strength Counsel overweight and obese adults with CV risk factors (high BP, hyperlipidemia and hyperglycemia), that lifestyle changes that produce even modest, sustained meaningful health benefits, and greater weight losses produces greater benefits. a. Sustained weight loss of 3% 5% is likely to clinically meaningful reductions in triglycerides, blood pressure, HbA1c, and the risk of developing type 2 diabetes. b. Greater amounts of weight loss will reduce BP, improve LDL C and HDL C, and reduce the need for medications to control BP, blood glucose and lipids as well as further reduce triglycerides and blood glucose. Class I = Treatment SHOULD be performed/administrated Grading Strength A = Strong Recommendation. There is high certainty based on evidence that the net benefit is substantial I A 1. Ann Intern Med 212;157:373 8; 2. recommendation statement/obesity in adults interventions1 Jensen MD et al. 213 AHA/ACC/TOS Obesity Guidelines 3

4 Use a Medical Model for Treatment Look AHEAD Study: Evidence of Longer term Effectiveness of Weight Loss BMI Treatment Options 25 kg/m 2 Lifestyle Modification 4% to 8% of initial Expected Efficacy weight Office-base, RD, commercial, internet 27 kg/m 2 + Comorbidities or 3 kg/m 2 Weight Loss Pharmacotherapy 5% to 12% of initial weight Orlistat, phentermine phenterime-topirimate ER Lorcaserin, naltrexone/bupropion SR, liraglutide 35 kg/m 2 + Comorbidities or 4 kg/m 2 (laparoscopic or open surgery) Obesity Surgery 14% to 33% of initial weight Adjustable gastric banding Sleeve gastrectomy Roux-en-Y gastric bypass Gastric balloons Vagal blockade 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % Intensive Lifestyle Intervention (ILI) Diabetes Support and Education (DSE) 92.8% 8% 73.6% 7% 6.8% 6% 68.% 5.3% 55.5% 5% 4% 37.5% 37.7% 3% 26.9% 2% 17.2% 13.3% 15.6% 11.% 1% 7.% 2.9%.7% % > % 5% 1% 15% > % 5% 1% 15% Year 1 Year 8 Jensen MD et al. 213 AHA/ACC/TOS Obesity Guidelines Look AHEAD Research Group. Obesity 214;22(1):S13 Patients with 5% WL AOMs = antiobesity medications XENDOS 72 Clinical Trial Data of AOMs Categorical 1 Year Weight Loss of 5% PBO ORL LOR PHEN/TPM ER BN LIRA 2 BLOOM BLOSSOM BLOOM-DM EQUIP CONQUER 7 3 SEQUEL* COR I COR-II COR-BMOD 54 Torgerson JS, et al. Diabetes Care. 24;27(1): ; Smith SR, et al. N Engl J Med. 21;363: ; Fidler MC, et al. J Clin Endocrinol Metab. 211;96: ; O'Neil PM, et al. Obesity (Silver Spring). 212;2: ; Allison DB, et al. Obesity (Silver Spring). 212;2(2):33 342; Gadde KM, et al. Lancet. 211;377: ; Garvey WT, et al. Am J Clin Nutr. 212;95:297 38; Greenway FL, et al. Lancet. 21;376:595 65; Apovian CM, et al. Obesity (Silver Spring). 213;21: ; Wadden TA, et al. Obesity (Silver Spring). 211;19:11 12; Hollander P, et al. Diabetes Care. 213;36: ; Wadden TA, et al. Int J Obes (Lond). 213;37: ; Pi-Sunyer X, et al. N Enlg J Med. 215;373:11-22; Astrup A, et al. Int J Obes (Lond). 212;36: COR-D SCALE Maintain SCALE Obesity Astrup et al (212) 73 Courtesy of S Kahan Risk Factors and Comorbidities with use of AOMs Parameter Orlistat Lorcaserin Phentermine/ topiramate ER Naltrexone/ bupropion SR Liraglutide 3. mg WC BP LDL HDL TG A1C Heart Rate BP = blood pressure; HDL = high-density lipoprotein; HR = heart rate; LDL = low-density lipoprotein; TG = triglycerides; WC = waste circumference. Xenical (orlistat) prescribing information. Qsymia (phentermine/topiramate ER) prescribing information. Belviq (lorcaserin) prescribing information. Contrave (naltrexone SR/bupropion SR) prescribing information. Saxenda (liraglutide 3. mg) prescribing information. Percent Weight Change Trajectories of Bariatric Surgery over 7 years from LABS* *Longitudinal Assessment of Bariatric Surgery Courcoulas AP et al. JAMA Surg 218 May 1;153(5): Rates of Comorbidity Reduction after Bariatric Surgery Disease or Symptom % improvement or remission at 2y % improvement or remission at 5 7 y % improvement or remission at 1 y Diabetes 72% 54% 3% Hypertension 24% 66% 41% Hypertriglyceridemia 62% 82% 4% Hypercholesterolemia 22% 53% 21% Sleep apnea 94% 66% Fatty liver disease 84% Stress urinary incontinence 64% resolved, 92% improved Depression 5% Vest AR, et al. Circ 213;127:

5 Health related Quality of Life Outcomes Associated with Weight Loss What is the role of the Registered Dietitian Nutritionist? IWQOL = Impact of Weight on Quality of Life SF 36 MCS = Medical Outcomes Study Short form Mental Component Summary SF 36 PCS = Medical Outcomes Study Short form Physical Component Summary EQ 5D = EuroQol Kolotkin RL, et al. Health and Quality of Life Outcomes 29. 7:53 Role of the RDN: Nutrition expert RDNs, as part of a multidisciplinary team, need to be current and skilled in weight management to effectively assist and lead efforts that can reduce the obesity epidemic. Provide appropriate medical nutrition therapy Be part of a multidisciplinary team Engage in strategies to assist with reimbursement for RDN s services Engage in advocacy Having accessible healthy and affordable foods, which is especially important to address health disparities Collect outcomes that document the importance of the RDN in improving health Raynor HA, Champagne CM. J Acad Nutr Diet 216;116: How Should We Conduct Ourselves When Counseling Patients with Obesity? Use Patient Centered Care defined as providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions Use Shared Decision making a process in which clinicians and patients work together to make decisions and select tests, treatments and care plans based on clinical evidence that balances risks and expected outcomes with patient preferences and values. Provide the Right Treatment to the Right Patient at the Right Time Conclusion Obesity, when defined as abnormal or excessive fat accumulation that presents a risk to health, is considered a disease We can identify patients who are at increased risk We have treatments that are effective in helping patients lose weight, reduce co morbidities, and improve quality of life There is evidence that individuals can maintain their weight loss We should use patient centered treatment and shared decision making when counseling patients about their weight. We should not impose our own beliefs domains.html 5

6 References GBD 215 Obesity Collaborators. Health effects of overweight and obesity in 195 countries in 195 countries over 25 years. N Engl J Med 217;377:13 27 Khan SS et al. Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. JAMA Cardiol 218 Apr 1;3(4): Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med 217;376: Garvey WT et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR COMPREHENSIVE MEDICAL CARE OF PATIENTS WITH OBESITY EXECUTIVE SUMMARY. Jensen MD et al. 213 AHA/ACC/TOS Guideline for the management of overweight and obesity in adults. Circulation. 213;129:S12 S138 Look AHEAD Research Group. Eight year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity 214;22(1):S13 Vest AR, et al. Surgical management of obesity and the relationship to cardiovascular disease. Circ 213;127: Raynor HA, Champagne CM. Position of the Academy of Nutrition and Dietetics: Interventions for the Treatment of Overweight and Obesity in Adults. J Acad Nutr Diet 216;116: Kolotkin RL, et al. One year health related quality of life outcomes in weight loss trial participants: comparison of three measures. Health and Quality of Life Outcomes 29. 7:53 6