Obesity and Comorbid Conditions Clarifying the Bariatric Referral Roadmap Moderator Louis J. Aronne, MD Clinical Professor of Medicine Weill Cornell Medical College Director, Comprehensive Weight Contro! Program New York-Presbyterian Hospital New York, New YorkPanelists Caroline M. Apovian, MD Professor of Medicine and Pediatrics Section of Endocrinology, Diabetes, and Nutrition Boston University School of Medicine Director, Nutrition and Weight Management Center Boston Medical Center Boston, Massachusetts Francesco Rubino,MD Associate Professor of Surgery Chief, Gastrointestinal Metabolic Surgery Weill Cornell Medical College New York, New York Alan R. Schwartz, MD Professor of Medicine Pulmonary and Sleep Medicine Johns Hopkins University School of Medicine Director, Johns Hopkins Sleep Center Johns Hopkins Bayview Medical Center Baltimore, MarylandActivity Goals ¢ Describe the relationship between obesity and its comorbidities, such as type 2 diabetes and OSA, as well as its effect on quality of life * Evaluate the clinical options to reduce obesity and related comorbidities + Develop patient counseling techniques and referral practices aimed at increasing the appropriate use of bariatric surgery to treat obesityWhy Treat Obesity? eee 7 Costs US healthcare expenditures associated with excess body weight among morbidly obese adults exceeded $147 billion!@) Mortality 2nd most frequent cause of preventable death in United States! }. : Associated Chronic Diseases fae Outranks smoking, drinking problems, BY Th ser or living in poverty’) a. Finkelstein EA, et al. Health Affairs. 2009:28:w822-831; b. Mokdad AH, et al. JAMA. 2004;291 1238-1245; c. Sturm R. Health Affairs, 2002;21:245-253; d. Sturm R, Wells KB. Pub/ Health. 2001 ;115:229-235.Disease Prevalence Attributable to Obesity* Type 2 diabetes Endometrial ca. Gallbladder dis. Osteoarthritis Hypertension CHD Breast cancer Colon cancer 0% 20% 40% 60% 80% "Obesity is defined as BMI > 29 kg/m? Adapted from: Wolf AM, et al. Obes Res. 1998:6:97-106.A Fat Cell Is an Endocrine Cell Fat cells generate and release a wide variety of peptides and metabolites that provide signals to distant parts of the body. Lactate CETP Prostaglandin Angiotensinogen PLTP Prostacyclin Leptin Monobutyrin Adiponectin Galectin-12. Free fatty acids PAI-1 TNF-alpha Adipsin (complement D Interleukin-6 pain P LPL CETP = cholesteryl ester transfer protein; LPL = lipoprotein lipase; PAl = plasminogen activator inhibitor; PLTP = phospholipid transfer protein; TNF = tumor necrosis factor Bray GA. J Nutr. 2002;132:3451S-3455S.Disease Prevalence Attributable to Obesity* (cont) Type 2 diabetes Endometrial ca. Gallbladder dis. Osteoarthritis Hypertension CHD Breast cancer Colon cancer 0% 20% 40% 60% 80% Obesity is defined as BMI > 29 kg/m? Adapted from: Wolf AM, et al. Obes Res. 1998:6:97-106.Guide for Selecting Obesity Treatment BMI, kg/m? 18.5-24.9 | 25-29.9 | 30-34.9 | 35-39.9 240 Diet, exercise, behavior treatment Pharmacotherapy Surgery Normal Overweight + Obese Severely Morbidly weight BMI BMI obese obese BMI 25-29.9 — 30-34.9 BMI BMI 18.5-24.9 35-39.9 240 NIH. http:/Awww.nhibi.nih.gov/guidelines/obesity/pretgd_c.pdfEffects of Moderate Weight Loss (5%-10%) Big Impact on Risk Factors ~5% 5%-10% WeightLoss WeightLoss HbAtc ye yu Blood pressure vy Pb) Hn Total cholesterol Qh Hu HDL cholesterol Da BD Triglycerides wy [a] vy le] a. Wing RR, et al. Arch Intern Med. 1987;147:1749-1753; b. Mertens IL, et al. Obes Res. 2000;8:270-278; c, Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S; d. Wood PD, et al. N Eng! J Med. 1991;325:461-466; e. Ditschunheit HH, et al. Eur J Clin Nutr. 2002;56:264-270.How Is Adult Obesity Treated? For select patients, 3 most effective Surgery treatment Can add 3%-8% 2 plscebo-subtracted b Pharmacotherapy weightloss 7 aN et (er- 1] list Activity Foundation of all 1 | weight management approaches Lifestyle Modification Obesity Society. www.obesityonline.orgPharmacotherapy Concerns + Large-scale need: Approximately 66% of Americans eligible for medication «FDA concerns over safety and effectiveness « Need to maintain weight loss with medication over prolonged time while balancing risk for adverse events with prolonged use + Insufficient number of trained individuals to administer medication and provide prolonged managementImprovement in Comorbidities Following Weight Loss: Diabetes Prevention Program Weight loss target: Lifestyle: 7% + 58% reduction in type 2 diabetesll + 41% reduction in metabolic syndromel) * 28% reduction in hypertension medication usel*) + 25% reduction in hyperlipidemia medication usell 1 kg (2.2 Ib) of weight loss = 16% reductionin development of diabetes a. Knowler WC, et al. NW Eng! J Med. 2002;346:393-403; b. Orchard TJ, et al. Ann Intern Med. 2005:142:611-619; c. Ratner R, et al, Diabetes Care. 2005;28:888-894.Expected Weight Loss With Currently Approved and Investigational Drugs Agent Drug(kg) Placebo (kg) Net weightloss (kg) Phentermine 6.8 28 4.0 Orlistat 7.3 3.5 3.0 Topiramate 45 17 2.8 Bupropion 6.0 28 3.2 Topiramate/phentermine 14.7 2.5 12.2 Bupropion/naltrexone 8.2 19 6.2 Bupropion/zonisamide 7.2 2.9 43 Pramlintide/metreleptin 12.7 No placebo 12.7 vs no placebo Lorcaserin 8.2 3.4 48 Liraglutide 7.2 2.8 44 Cetilistat 43 28 15 Tesofensine 11.2 2 9.2 Velneperit 71 43 2.8 Powell AG, et al. Clin Pharmacol Ther. 2011;90:40-51.Sleep Apnea Severity in Bariatric Cohorts Author Baseline AHI (95% Cl)| Weight Charuzi +o 60.80 (50.65, 70.95) 9.77 Sugerman +a 64.00 (51.91, 76.09) 8.63 Pillar —a— 40.00 (24.91, 55.09) 7.07 Scheuller { fl 96.90 (74.48, 119.32) 4.39 Guardiano —tr— 55.00 (33.52, 76.48) 4.66 Rashied a 56.00 (48.32, 63.68) 11.29 Valencia-Flores a 51.70 (44.44, 58.96) 11.56 Dixon +a 61.60 (49.10, 74.10) 8.40 Kaltra —a— ' 22.20 (6.23, 38.17) 6.66 Haines a: 51.00 (50.22, 51.78) 14.24 Fritscher ot 66.00 (47.08, 84.92) 5.49 Lettieri a 47.80 (34.28, 61.32) 7.85 [overan] <> 4100.00 ro + 1 0515 30 100 60 Apnea-hypopnea AHI = apnea-hypopnea index: Cl = confidence interval Greenburg DL, et al. Am J Med, 2009;122:535-542.Pathogenesis of Respiratory Disturbances in Obesity OBESITY obstruction \ | Arousals ¥$a0, 40, | 4 | Pharyngeal 4 FRC Hypoventilation IHypersomnolence Cor pulmonale Respiratory failure Hypertension, glucose intolerance, cardiovascular disease ASLEEP FRC = functional residual capacity AWAKE Diagram courtesy of Alan Schwartz, MD.Obesity and Upper Airway Obstruction During Sleep NORMAL APNEIC Image courtesy of Alan Schwartz, MD.Pathogenesis of Respiratory Disturbances in Obesity (cont) OBESITY Pharyngeal Lat obstruction 4 FRC Hypoventilation Arousals ¥Sa0, 40, Respiratory IHypersomnolence Cor pulmonale failure Hypertension, glucose intolerance, cardiovascular disease ASLEEP AWAKE Diagram courtesy of Alan Schwartz, MD.Cumulative Incidence of Cardiovascular Events Effects of Sleep Apnea Severity and CPAP Treatment Fatal Events Nonfatal Events 8 — Controls 35 —— Controls 304 |—— snorers 30 |—— Snorers — Mild OSAH sg 25-| | Mild OSA 3 ea ~ — severe & 20-| | Severe OSAH 20 c —— OSAH With CPAP, § —— OSAH With CPAF Sis a ° 3 £10 = T 1 oF T T 0 36 72 108 148 0 36 Time From Diagnosis, mo CPAP = continuous positive airway pressure; OSAH = OSA and hypopnea Marin JM, et al. Lancet. 2005;365:1046-1053,Bariatric Surgeries in the United States Year No. of Bariatric Surgeries* 19984] 15,000 2000!) 32,000 2002I4) 72,000 200411 120,000 2006! 175,000 + Increasing number of patients will require more postoperative management (complications, maintenance, failures) + Many healthcare professionals at some point will treat patients who have undergone bariatric surgery *Numbers are approximate. a. Santry HP, et al. JAMA. 2005;294:1909-1917. b. American Society for Metabolic and Bariatric Surgery. www.asmbs.orgBariatric Surgery: Common Procedures Stomach ouch Bypassed _ Ps Pouch pottion of Bile duct ~ ‘stomach Gastric ) *sleeve’ Duodenum Pylotus \ \ Long \ Roux-limb Excised , “een stomach “Commen limb Common _Bitlepancreatic Colon limb limb R M4 Biliopancreatic Gastric band aie Ce ho) CT) aC TS gastrectomy erie yy ot Rosenthal RJ, Jones DB, eds. Weight Loss Surgery: A Multidisciplinary Approach. Matrix Medical Communications; 2008 American Society for Metabolic and Bariatric Surgery. www.asmbs.org.Types of Surgeries Performed in the United States Approximate BestReported Procedure Percentage of Excess Body Con tons Procedures WeightLoss P pee ss 50% 75% 8%-10% Laparoscopic adjustable band 35% 50% 2% ceaa 10% 59%-61% 2% Biliopancreatic diversion with < 10% > 75% 10% duodenal switch The death rate from gastric bypass is no higher PURE lael mi CT gel lata Rosenthal RJ, Jones DB, eds. Weight Loss Surgery: A Multidisciplinary Approach. Matrix Medical Communications; 2008Sleep Apnea Is a Predictor of an Adverse Outcome From Bariatric Surgery —a- History of DVT but no OSA —-History DVT and OSA —=—No history of DVT or OSA —#—History of OSA but no DVT 8 0.20 § 0.18 £0.16 90.14 2 0.12 oO 3 0.10 0.08 30.08 = 0.04 § 0.02 Oo ¢ 0.004 : : r - > 1 : 1 30 35 40 45 50 55 60 65 70 Body Mass Index DVT = deep vein thrombosis LABS Consortium. N Eng/ J Med. 2009;361:445-454.Effects of CPAP on Postsurgical Complications Group 1(OSAS) 1B (n = 88) — Nohome Group 2 1A CPAP) Home CPAP Total (control) (n=36) (n= 32) (n= 33) (n=101) (n= 101) Pvalue Any complication 18(50) 12(37.5) 9(27.3) 39 (39) 18(18) 001 Serious 12(33.3) —-9(28.1) 3(8.1) 24(24) 9(9) 004 complication Total ICU 14(38.9) 8(25.0) 1(3.0) 23.(23) 8(8) 003 Unplanned ICU 12(33.3)-—-7(21.9) 13.0) 20 (20) 66) 003 Hospitalstay,d 74429 69433 60424 est28 8 B41+44 007 No home CPAP Home CPAP (n= 68) (n= 33) Pvalue Any complication 30 (44.1) 9(27.3) 40 Serious complication 2130.9) 318.1) 02 Total ICU 22(32.3) 103) 001 Unplanned ICU 19(27.9) 13) 003 Hospital stay, dl 72+ 34 60+ 24 03 Gupta R, et al. Mayo Clin Proceed. 2001Sleep Apnea Severity Following Bariatric Surgery Charuzi e 8.00 (4.63, 11.37) 11.35 Sugerman = 26.00 (17.94, 34.06) 7.12 Pillar = 24.00 (11.95, 36.05) 4.56 Scheuller FP 11.30 (3.71, 18.89) 7.50 Guardiano i 14.00 (2.22, 25.78) 4.70 Rashied re 23.00 (18.86, 27.14) 10.67 Valencia-Flores = 13.40 (8.66, 18.14) 10.14 Dixon = 13.40 (8.30, 18.50) 977 Kaltra =| 5.60 (0.37, 10.83) 9.64 Haines a 16.00 (0.37, 10.83) 12.97 Fritscher +e 23.70 (9.95, 37.45) 3.82 Lettieri i 24,50 (17.26, 31. Boe 779 Greenburg DL, et al. Am J Med. 2009;122:535-542. ' ! Bev] ieee tee] 00 0515 30 ariatric Surgery Apnea- Hypopnea ms 69 (49.04, 60.34)Lap band Patient preference for lowest risk, reversible Short hospital stay Least disability BMI 30-35 History of alcohol abuse Needs adjustment Vitamins important, not critical Diabetes or sleep apnea, Who Gets Which Procedure? Roux-en-Y gastric bypass + Patient preference for lowest weight + Diabetes, BMI > 35 + Vitamins critical + Noalcohol abuse Sleeve gastrectomy + Patient preference for fewest problems with eating * Vitamins important, not criticalMeta-Analysis of Clinical Outcomes From Bariatric Surgery * 22,094 subjects: 73% female, mean age 39, mean BMI 47 + Percent excess body weight loss: 61% - 48% for banding - 62% for Roux-en-Y gastric bypass - 70% for biliopancreatic diversion or biliopancreatic diversion with a duodenal switch + 30-day operative mortality - 0.1% for banding - 0.5% for gastric bypass - 1.1% for biliopancreatic diversion or biliopancreatic diversion with a duodenal switch + Outcomes - Diabetes: 77% resolved - Hyperlipidemia: 70% improved - Hypertension: 62% resolved - OSA: 86% resolved BuchwaldH, et al. JAMA. 2004:292:1724-1737.Indications for Bariatric Surgery * An available weight loss option for well-informed and motivated patients with - BMI= 40 kg/m? - BMI 235 kg/m2who have comorbid conditions* and acceptable operative riskll + FDA has recently approved lap band surgery for patients with BMI 30-35 kg/m? who have comorbid conditions* + Patients should have tried but failed an adequate exercise and diet program! *Comorbid conditions include hypertension, impaired glucose tolerance, diabetes, hyperlipidemia, and OSA.EI a. NIH. http://www.nhibi.nih.gov/guidelines/obesity/ob_gdins.pdf. b. Snow V, et al. Ann Intern Med. 2005:142:525-531.Use of Bariatric/Metabolic Surgery + Low mortality + Low morbidity + Lifesaving + Cost-effective < 2% of eligible patients in the United States undergo metabolic surgery. Rosenthal Rd, Jones DB, eds. Weight Loss Surgery: A Multidisciplinary Approach. Matrix Medical Communications; 2008Short-term Obesity Therapy Does Not Result in Long-term Weight Loss 5 i Diet alone 2 0 @ Behavior therapy = ACombined therapy 35 s & o -10 D> 5 6715 -20 r ; , Baseline End of 1-Year 5-Year Treatment Follow-up Follow-up Wadden TA, et al. Int J Obes. 1989:13 (Supp! 2):39-46.Mortality Rates Following Common Operations in US Hospitals!! Abdominal Pediatric Aortic Esophageal Hip Pancreatic Heart Aneurysm CABG Craniotomy Resection Replacement Resection Surgery Number of hospitals performing 2485-1086 1600 1717 3445 1302 458 operation National average 3.9 3.5 10.7 21 0.3 8.3 5.4 mortality rate, % Annual hospital 30491 12 5 24 8 4 caseloads, median Bariatric surgery mortality % (> 110,000 patients)!*) a. Dimick JB, et al. JAMA. 2004;292:847-851; b. Pories WJ. J Clin Endocrinol Metab. 2008;93:S89- 96.Cultural Barriers/Misperceptions mene Bisesse Treatment peace emphasized / nv * Surgery, >. B 2 = radiotherapy, Ka chemotherapy + Lifestyle smock coca modification Risk Factor Disease Treatment 4 emphasized ; > => + Lifestyle modification 3 + Surgery, drug therapy Overeating Sedentary Lifestyle ObesityThank you for participating in this activity. To proceed to the online CME test, click on the Earn CME Credit link on this page.