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

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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

Foundational Concepts

Defining Obesity

• 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)

http://www.who.int/topics/obesity/en/

Obesity: In the top three global social burdens

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) GDP, $ trillion Global GDP % Historical trend 2.1 2.9 Smoking 2.1 2.8 Armed violence, war, and terrorism 2.0 2.8 Obesity 1.4 2.0 Alcoholism 1.3 1.7 Illiteracy 1.0 1.3 Climate change 0.9 1.3 Outdoor air pollution 0.7 1.0 Drug use 0.7 1.0 Road accidents 0.4 0.6 Workplace risks 0.4 0.5 Household air pollution 0.3 0.5 Child and maternal undernutrition 0.3 0.4 Unsafe sex 0.1 0.1 Poor water and sanitation Selected global social burdens

Obesity is associated with multiple comorbidities

Metabolic, Mechanical and Mental

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– 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 2009;6:A48

Metabolic

Type 2 diabetes Prediabetes Cardiovascular diseases

• Stroke
• Dyslipidaemia
• Hypertension
• Coronary artery disease
• Coronary heart failure
• Pulmonary embolism

I nfertility NAFLD Cancers* Gout Thrombosi s Asthma Gallstones

Mental

Depression Physical functioning

Mechanical

Sleep Apnoea I ncontinence Arthrosis Chronic back pain

NAFLD, non-alcoholic fatty liver disease * Including breast, colorectal, endometrial, esophageal, kidney, ovarian, pancreatic and prostate

Anxiety

Global DALYs associated with high BMI

1990 and 2015

GBD 2015 Obesity Collaborators. N Engl J Med 2017;377:13–27 DALYs, disability‐adjusted life‐years

10 10 8 8 6 4 2 6 4 2 20 20 25 25 30 35 35 40 45 50 50 30 40 45 Body mass index Body mass index Disability‐adjusted life‐years (in millions) Disability‐adjusted life‐years (in millions) Musculoskeletal disorders Cardiovascular diseases Cancers Chronic kidney disease Diabetes Mellitus

1.6% 2.1% 35.4% 25.6% 0.3% 3.4% 3.3% 11.5% 3.1% 5.8% 2.1% 4.1% 0.8% 0.3% 0.6% 2.8% 33.7% 4.2% 18.0% 4.7% 1.6% 18.7% 2.9% 6.4% 2.8% 0.8% 0.3% 0.4% 2.5% 0.2%

Disability‐adjusted life‐years in 1990 Disability‐adjusted life‐years in 2015

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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

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

Zheng Y et al, JAMA 2017;318:255‐269

“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.”

Association of Weight Gain from Early (18 – 21 years) to Middle (55 years) Adulthood with Risk of Developing Major Chronic Disease

 No self‐reported history of chronic disease  No cognitive decline  No physical limitations Zheng Y et al, JAMA 2017;318:255‐269

Obesity increases lifetime risk of CVD morbidity

Khan SS et al. JAMA Cardiol2018Apr 1;3(4):280‐287. 3.2 Million person years of follow up from 1964 to 2015 All participants were free of clinical CVD at baseline

Middle‐aged men Middle‐aged women

Follow‐up, years Follow‐up, years

CVD, cardiovascular disease ‐20 ‐15 ‐10 ‐5 30 to <35 35 to <40 ≥40

Obesity is associated with impaired physical function

Female Male

Hopman et al. Qual Life Res 2007;16:1595–603

Physical functioning compared with normal weight (BMI 18.5 to <25) SF‐36, Short Form‐36

Change in SF‐36 domain score BMI (kg/m2)

 Angiotensinogen  PAI‐1  FFA  prostaglandins  Estrogen  Adiponectin  Leptin

Hypertension Thrombosis Inflammation Type 2 diabetes Dyslipidemia Arthritis Stroke, Heart attack PVD Asthma

Tissue  Adipose Tissue

 Insulin

LIPOTOXICITY

The link between pathophysiology of obesity and associated comorbid conditions

Lipotoxicity – Products of fat tissue

Cancer

 Adipsin  Resistin  TNFα  EGF  TNF ß  IL6 Reviewed in Kershaw EE, et al. J Clin Endocrinol Metab. 2004; 89: 2548-2556; Hajer GR et al. European Heart Journal. 2008; 29: 2959–2971 TNFα =tumor necrosis factor alpha; EGF = epidermal growth factor; PAI‐1 = plasminogen activator inhibitor‐1; IL6 = interleukin 6 CHD

Adipokine synthesis Adipose tissue macrophages and other inflammatory cells Pro‐inflammatory cytokines Impaired insulin signalling and insulin resistance Insulin

T2D CHF Stroke CKD Adiposity

Lipid production Hydrolysis of triglycerides Activity of the sympathetic nervous system

NAFLD NASH Cirrhosis

Release of fatty acids Lipotoxicity Dyslipidaemia Activity of the renin‐ angiotensin‐aldosterone system Mechanical stress Systemic and pulmonary hypertension Pharyngeal soft tissue Mechanical load on joints Intra‐abdominal pressure Renal compression

GERD Barrett’s oesophagus Oesophageal adenocarcinoma Osteoarthritis OSA

Excess adiposity leads to major risk factors and common chronic diseases

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 2017;376:254–66

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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

• 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– 9; 7. Warkentin et al. Obes Rev 2014;15:169–82; 8. Wright et al. J Health Psychol 2013;18:574–86

Weight loss improves obesity related comorbidities

Reduction in CV mortality2 Improvements in blood lipid profile3 Improvements in blood pressure4

Benefits of 5–10% weight loss

Reduction in risk of type 2 diabetes1 Improvements in severity of

• bstructive sleep

aponea5,6 Improvements in health‐related quality

• f life7,8

AACE Obesity Guidelines

https://www.aace.com/files/guidelines/ObesityExecutiveSummary.pdf

Recommendation Grade Screen all adults for obesity Clinicians should offer or refer patients with a BMI of 30 kg/m2 or higher to intensive, multicomponent behavioral interventions1 B Clinicians offer or refer adults with a BMI of 30 kg/m2 or higher to intensive, multicomponent behavioral interventions2 B

US Preventive Services Task Force (USPSTF) Recommendation Statements

• 1. Ann Intern Med 2012;157:373–8; 2. www.uspreventiveservicestaskforce.org/Page/Document/draft‐recommendation‐statement/obesity‐in‐adults‐interventions1

BMI, body mass index

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.

AHA/ACC/TOS Obesity Guidelines

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

• f 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.

I A

 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

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Use a Medical Model for Treatment

Treatment Options BMI ≥25 kg/m2 ≥27 kg/m2 + Comorbidities

• r ≥30 kg/m2

≥35 kg/m2 + Comorbidities or ≥40 kg/m2 (laparoscopic or

• pen surgery)

Expected Efficacy

4% to 8% of initial weight Office-base, RD, commercial, internet 5% to 12% of initial weight Orlistat, phentermine phenterime-topirimate ER Lorcaserin, naltrexone/bupropion SR, liraglutide 14% to 33% of initial weight Adjustable gastric banding Sleeve gastrectomy Roux-en-Y gastric bypass Gastric balloons Vagal blockade Lifestyle Modification Weight Loss Pharmacotherapy Obesity Surgery Jensen MD et al. 2013 AHA/ACC/TOS Obesity Guidelines

Look AHEAD Study: Evidence of Longer‐term Effectiveness of Weight Loss

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 80% 70% 60% 50% 40% 30% 20% 10% 0% 92.8% 55.5% 68.0% 13.3% 37.7% 15.6% 2.9% 0.7% 73.6% 60.8% 50.3% 37.5% 26.9% 17.2% 11.0% 7.0% > 0% ≥ 5% ≥ 10% ≥ 15% > 0% ≥ 5% ≥ 10% ≥ 15%

Year 1 Year 8

Intensive Lifestyle Intervention (ILI) Diabetes Support and Education (DSE)

Look AHEAD Research Group. Obesity 2014;22(1):S13

Torgerson JS, et al. Diabetes Care. 2004;27(1):155–161; Smith SR, et al. N Engl J Med. 2010;363:245–256; Fidler MC, et al. J Clin Endocrinol Metab. 2011;96:3067-3077; O'Neil PM, et al. Obesity (Silver Spring). 2012;20:1426–1436; Allison DB, et al. Obesity (Silver Spring). 2012;20(2):330–342; Gadde KM, et al. Lancet. 2011;377:1341–1352; Garvey WT, et al. Am J Clin Nutr. 2012;95:297–308; Greenway FL, et al. Lancet. 2010;376:595–605; Apovian CM, et al. Obesity (Silver Spring). 2013;21:935-943; Wadden TA, et al. Obesity (Silver Spring). 2011;19:110–120; Hollander P, et al. Diabetes Care. 2013;36:4022–4029; Wadden TA, et al. Int J Obes (Lond). 2013;37:1443-1451; Pi-Sunyer X, et al. N Enlg J Med. 2015;373:11-22; Astrup A, et al. Int J Obes (Lond). 2012;36:843-854.

PBO ORL LOR PHEN/TPM ER BN LIRA 45 20 25 16 17 21 30 16 17 41 19 22 27 28 72 45 47 45 67 70 75 48 67 54 44 50 64 73 20 40 60 80 XENDOS BLOOM BLOSSOM BLOOM-DM EQUIP CONQUER SEQUEL* COR I COR-II COR-BMOD COR-D SCALE Maintain SCALE Obesity Astrup et al (2012) Patients with ≥5% WL

Clinical Trial Data of AOMs – Categorical 1 Year Weight Loss of ≥ 5%

Courtesy of S Kahan

AOMs = antiobesity medications

Parameter Orlistat Lorcaserin Phentermine/ topiramate ER Naltrexone/ bupropion SR Liraglutide 3.0 mg

WC      BP      LDL      HDL      TG      A1C      Heart Rate   ‐  

Improvements in Risk Factors and Comorbidities with use of AOMs

BP = blood pressure; HDL = high-density lipoprotein; HR = heart rate; LDL = low-density lipoprotein; TG = triglycerides; WC = waste circumference. Xenical (orlistat) prescribing information. http://www.gene.com/download/pdf/xenical_prescribing.pdf; Qsymia (phentermine/topiramate ER) prescribing information. https://qsymia.com/pdf/prescribing- information.pdf; Belviq (lorcaserin) prescribing information. www.belviq.com/documents/Belviq_Prescribing_information.pdf; Contrave (naltrexone SR/bupropion SR) prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf; Saxenda (liraglutide 3.0 mg) prescribing information. http://novo-pi.nnittest.com/saxenda.pdf.

Percent Weight Change Trajectories of Bariatric Surgery over 7 years from LABS*

Courcoulas AP et al. JAMA Surg 2018 May 1;153(5):427‐434

*Longitudinal Assessment of Bariatric Surgery

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 10 y Diabetes 72% 54% 30% Hypertension 24% 66% 41% Hypertriglyceridemia 62% 82% 40% Hypercholesterolemia 22% 53% 21% Sleep apnea 94% 66% Fatty liver disease 84% Stress urinary incontinence 64% resolved, 92% improved Depression 50%

Vest AR, et al. Circ 2013;127:945‐959

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Health‐related Quality of Life Outcomes Associated with Weight Loss

Kolotkin RL, et al. Health and Quality of Life Outcomes 2009. 7:53 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

What is the role of the Registered Dietitian Nutritionist?

• “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.”

Raynor HA, Champagne CM. J Acad Nutr Diet 2016;116:129‐147.

Role of the RDN: Nutrition expert

• 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

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

• utcomes with patient preferences and values.
• Provide the Right Treatment to the Right Patient at the Right Time

https://www.ahrq.gov/talkingquality/measures/six‐domains.html

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

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References

• GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries in 195 countries over 25
• years. N Engl J Med 2017;377:13–27
• Khan SS et al. Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of
• Morbidity. JAMA Cardiol2018 Apr 1;3(4):280‐287.
• HeymsfieldSB, WaddenTA. Mechanisms, Pathophysiology, and Management of Obesity. N EnglJ Med2017;376:254–

66

• 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 . https://aace.com/files/guidelines/ObesityExecutiveSummary.pdf

• Jensen MD et al. 2013 AHA/ACC/TOS Guideline for the management of overweight and obesity in adults. Circulation.

2013;129:S102–S138

• Look AHEAD Research Group. Eight‐year weight losses with an intensive lifestyle intervention: the look AHEAD study.

Obesity 2014;22(1):S13

• Vest AR, et al. Surgical management of obesity and the relationship to cardiovascular disease. Circ 2013;127:945‐959
• Raynor HA, Champagne CM. Position of the Academy of Nutrition and Dietetics: Interventions for the Treatment of

Overweight and Obesity in Adults. J AcadNutr Diet 2016;116:129‐147

• KolotkinRL, 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 2009. 7:53