3/11/2019 Foundational Concepts Debate: A Conversation on Weight - PDF document

3/11/2019 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 Selected global social burdens Global GDP % Historical trend Smoking 2.1 2.9 Armed violence, war, and terrorism 2.1 2.8 Obesity 2.0 2.8 • Overweight and obesity are defined as abnormal or excessive fat Alcoholism 1.4 2.0 Illiteracy accumulation that presents a risk to health 1.3 1.7 Climate change 1.0 1.3 • A crude population measure of obesity is the body mass index Outdoor air pollution 0.9 1.3 (BMI) Drug use 0.7 1.0 Road accidents 0.7 1.0 Workplace risks 0.4 0.6 Household air pollution 0.4 0.5 Child and maternal undernutrition 0.3 0.5 Unsafe sex 0.3 0.4 Poor water and sanitation 0.1 0.1 GDP, $ trillion http://www.who.int/topics/obesity/en/ McKinsey Global Institute. Overcoming obesity: An initial economic crisis. November 2014. Available at: www.mckinsey.com/industries/healthcare‐systems‐and‐ services/our‐insights/how‐the‐world‐could‐better‐fight‐obesity (Accessed 5 May 2017) Obesity is associated with multiple comorbidities Global DALYs associated with high BMI Metabolic, Mechanical and Mental 1990 and 2015 Sleep Apnoea Disability‐adjusted life‐years in 1990 Disability‐adjusted life‐years in 2015 Depression Metabolic Cardiovascular diseases 10 10 1.6% • Stroke Anxiety • Dyslipidaemia Disability‐adjusted life‐years (in Disability‐adjusted life‐years (in Mechanical 8 8 2.8% • Hypertension • Coronary artery disease Asthma • Coronary heart failure Mental 6 1.6% 6 millions) millions) • Pulmonary embolism NAFLD 2.1% 18.7% 33.7% Chronic back pain 4 4 Gallstones 25.6% 0.2% Cancers* 35.4% 2.9% 4.2% Type 2 diabetes 0.3% I nfertility 2 2 Prediabetes 2.5% 4.1% 3.3% 3.4% 6.4% 18.0% 0.4% Physical functioning 0.6% 5.8% 0.8% 11.5% 0.8% I ncontinence 2.1% 2.8% 4.7% 0.3% 3.1% 0.3% 0 0 Thrombosi s 20 25 30 35 40 45 50 20 25 30 35 40 45 50 Arthrosis Body mass index Body mass index Gout Cancers NAFLD, non-alcoholic fatty liver disease Musculoskeletal disorders Cardiovascular diseases Chronic kidney disease Diabetes Mellitus * Including breast, colorectal, endometrial, esophageal, kidney, ovarian, pancreatic and prostate Adapted from Sharma AM. Obes Rev . 2010; 11: 808-9; Guh et al. BMC Public Health 2009; 9: 88; Luppino et al. Arch Gen Psychiatry 2010;67:220– DALYs, disability‐adjusted life‐years 9; Simon et al. Arch Gen Psychiatry 2006;63:824–30; Church et al. Gastroenterology 2006;130:2023–30; Li et al. Prev Med 2010;51:18–23; Hosler. Prev Chronic Dis GBD 2015 Obesity Collaborators. N Engl J Med 2017;377:13–27 2009;6:A48 1

3/11/2019 Association of Weight Gain from Early (18 – 21 years) to Middle (55 years) Adulthood Association of Weight Gain from Early (18 – 21 years) to Middle (55 years) with Risk of Developing Major Chronic Disease Adulthood with Risk of Developing Major Chronic Disease* *T2DM, hypertension, CVD, obesity‐related cancer, cholelithiasis, osteoarthritis, cataract, death 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  No self‐reported history of chronic disease  No cognitive decline “Those who gained more weight were more likely to be physically inactive, to be never smokers, to have  No physical limitations unhealthy dietary habits, and to have a higher prevalence of chronic diseases at the age of 55 years.” Zheng Y et al, JAMA 2017;318:255‐269 Zheng Y et al, JAMA 2017;318:255‐269 Obesity increases lifetime risk of CVD morbidity Obesity is associated with impaired physical function BMI (kg/m 2 ) Middle‐aged men Middle‐aged women 30 to <35 35 to <40 ≥40 0 Change in SF‐36 domain score ‐5 ‐10 ‐15 Female Male ‐20 Follow‐up, years Follow‐up, years 3.2 Million person years of follow up from 1964 to 2015 Physical functioning compared with normal weight (BMI 18.5 to <25) All participants were free of clinical CVD at baseline SF‐36, Short Form‐36 CVD, cardiovascular disease Khan SS et al. JAMA Cardiol 2018Apr 1;3(4):280‐287. Hopman et al. Qual Life Res 2007;16:1595–603 Lipotoxicity – Products of fat tissue Excess adiposity leads to major risk factors and common chronic diseases The link between pathophysiology of obesity and associated comorbid conditions Adiposity Hypertension Inflammation  Adiponectin Adipokine synthesis Lipid production Activity of the sympathetic Activity of the renin‐ Mechanical stress nervous system angiotensin‐aldosterone  TNFα  Angiotensinogen system Adipose tissue macrophages Arthritis Hydrolysis of triglycerides  TNF ß Dyslipidemia and other inflammatory cells   FFA  Insulin  IL6 Asthma Adipose Release of fatty acids Intra‐abdominal  prostaglandins Pro‐inflammatory Renal Mechanical  EGF Pharyngeal soft cytokines load on joints pressure compression tissue Tissue Tissue  Adipsin Lipotoxicity Dyslipidaemia Cancer Type 2 diabetes  PAI‐1 Impaired insulin signalling Systemic and and insulin resistance  Resistin  Estrogen pulmonary Stroke, NAFLD hypertension OSA Osteoarthritis  Leptin NASH Heart attack Thrombosis Cirrhosis PVD Insulin CHD LIPOTOXICITY GERD Barrett’s oesophagus T2D CHF Oesophageal adenocarcinoma Stroke TNFα =tumor necrosis factor alpha; EGF = epidermal growth factor; PAI‐1 = plasminogen activator inhibitor‐1; IL6 = CKD interleukin 6 Reviewed in Kershaw EE, et al. J Clin Endocrinol Metab . 2004; 89: 2548-2556; Hajer GR et al. CHD, coronary heart disease; CHF, coronary heart failure; CKD, chronic kidney disease; GERD, gastroesophageal reflux disease; NAFLD, nonalcoholic fatty liver European Heart Journal. 2008; 29: 2959–2971 disease; NASH, nonalcoholic stereohepatitis; OSA, obstructive sleep apnea; T2D, type 2 diabetes. Heymsfield SB, Wadden TA. NEJM 2017;376:254–66 2

3/11/2019 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 https://www.aace.com/files/guidelines/ObesityExecutiveSummary.pdf Weight loss improves obesity related comorbidities AACE Obesity Guidelines Benefits of 5–10% weight loss Reduction in risk of Reduction in CV Improvements in Improvements in Improvements in Improvements in type 2 diabetes 1 mortality 2 blood lipid profile 3 blood pressure 4 severity of health‐related quality obstructive sleep of life 7,8 aponea 5,6 1. Knowler et al . N Engl J Med 2002;346:393–403; 2. Li et al . Lancet Diabetes Endocrinol 2014;2:474–80; 3. Datillo et al . Am J Clin Nutr 1992;56:320–8; 4. Wing et al . Diabetes Care 2011;34:1481–6; 5. Foster et al . Arch Intern Med 2009;169:1619–26; 6. Kuna et al . Sleep 2013;36:641– https://www.aace.com/files/guidelines/ObesityExecutiveSummary.pdf 9; 7. Warkentin et al . Obes Rev 2014;15:169–82; 8. Wright et al . J Health Psychol 2013;18:574–86 US Preventive Services Task Force (USPSTF) Recommendation Statements AHA/ACC/TOS Obesity Guidelines Recommendation Class Grading Strength Recommendation Grade Counsel overweight and obese adults with CV risk factors (high BP, hyperlipidemia and hyperglycemia), that lifestyle changes that Screen all adults for obesity produce even modest, sustained meaningful health benefits, and Clinicians should offer or refer patients with a BMI of 30 kg/m 2 or higher to B greater weight losses produces greater benefits. intensive, multicomponent behavioral interventions 1 a. Sustained weight loss of 3% ‐ 5% is likely to clinically meaningful I A Clinicians offer or refer adults with a BMI of 30 kg/m 2 or higher to intensive, reductions in triglycerides, blood pressure, HbA1c, and the risk multicomponent behavioral interventions 2 B 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, B = The USPSTF recommends the service. There is high certainty that the net benefit is moderate or blood glucose and lipids as well as further reduce triglycerides there is moderate certainty that the net benefit is moderate to substantial. and blood glucose. BMI, body mass index  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 Jensen MD et al. 2013 AHA/ACC/TOS Obesity Guidelines 1. Ann Intern Med 2012;157:373–8 ; 2. www.uspreventiveservicestaskforce.org/Page/Document/draft‐recommendation‐statement/obesity‐in‐adults‐interventions1 3