Update on Bariatrics and she has remained morbidly obese Past - PDF document

Case Presentation: Patty 33 year-old woman with morbid obesity. 5’5” 262 lbs BMI 44 Morbidly obese since childhood. She has tried Weight Watchers, Curves, South Beach Diet, Low Carb Diet, Atkins Diet, Slim-Fast, Nutrisystem and the UCSF Medically Managed Weight Loss Program. Although she has been able to lose some weight from diets and exercise, over time the weight has always returned, Update on Bariatrics and she has remained morbidly obese Past Medical History Hypertension Migraine Diabetes mellitus (HBA1C 6.7%) Jonathan Carter, MD Asthma Associate Professor of Surgery Intertrigo 10/12/18 Urinary stress incontinence Polycystic ovarian syndrome What can we offer Patty? 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight. 2. We have new insights about why diets fail in the long run. Patty 3. No effective and durable drug therapy for severe obesity exists. 262 lbs 4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, hysterectomy. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus. 1 | [footer text here]

1990 What can we offer Patty? 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight. 2. We have new insights about why diets fail in the long run. 3. Drug therapy has a modest effect on weight. 4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, hysterectomy. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus. https://stateofobesity.org/adult-obesity/ 2000 1995 2 | [footer text here]

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2015 2016 Why is obesity unhealthy? Obesity reduces life expectancy RESPIRATORY CARDIOVASCULAR obstructive sleep apnea Hypertension Pickwickian syndrome Congestive Heart Failure asthma Cor pulmonale Years of lost life expectancy in women GASTROINTESTINAL Varicose veins GERD Pulmonary embolism Fatty liver disease / NASH Coronary artery disease 10 Hernia ENDOCRIN E Colon cancer Metabolic syndrome 8 GENITOURINARY Type 2 diabetes Urinary stress incontinence Dyslipidemia 6 Obesity-related glomerulonephropathy Polycystic ovary syndrome Hypogonadism Amenorrhea, infertility, menstrual disorders Breast and uterine cancer 4 MUSCULOSKELETAL Pregnancy complications Gout NEUROLOGIC Osteoarthritis Stroke Lower back pain Idiopathic intracranial hypertension Carpal tunnel syndrome Meralgia paresthetica SKIN 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 Dementia dermatoliposclerosis PSYCHOLOGIC lymphedema BODY MASS INDEX Depression cellulitis Low self-esteem intertrigo Body image disturbance hidradenitis suppurativa Social stigmatization Mechanick et al. SOARD 2008 6 | [footer text here]

What can we offer Patty? 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight. 2. We have new insights about why diets fail in the long run. 3. Drug therapy has a modest effect on weight. 4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, hysterectomy. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus. Randomly assigned 811 patients to 4 groups: low fat, low protein high fat, high protein low fat, high protein high fat, low protein Intensive group/individual instructional sessions Intensive follow-up to 2 years 7 | [footer text here]

14 participants of “The Biggest Loser” competition Participants were studied 1. prior to participation in the show 2. at the end of the 30 week competition 3. 6 years later 30 weeks: VLCD exercise Outcome variables Methodology Measured resting metabolic • Indirect calorimetry rate (RMR) • Fast for 12 hours, then lay supine • Breath into metabolic cart for 15 min • Measure O2 intake and CO2 emission • Calculate Resting Metabolic Rate (RMR) Body composition • By dual-energy x-ray absorptiometry • Measures Fat Mass (FM) and Fat-Free Mass (FFM) Predicted RMR Indirect calorimetry to measure resting metabolic rate Fast for 12 hours Breathe into Total energy expenditure • Clearance of 18 O H 2 O and 2 H H 2 O over 2 weeks • CO2 generation calculated, used to calculate TEE 8 | [footer text here]

Metabolic Adaptation = RMR (measured) – RMR (predicted) = the difference between what you are actually burning versus what you should be burning based upon your body composition, age, and sex. Reflects the body’s ability to slow metabolic rate in order to preserve fat mass In lay terms, is the body’s “starvation mode” What happened at 6 years? Body weight change Fat-free mass change Fat mass change in kilograms in kilograms in kilograms 9 | [footer text here]

What happened at 6 years? Metabolic adaptation foils long-term attempts at dieting Obesity is not a disease of gluttons and sloths. The body acts to preserve the fat mass set point. Diet and exercise do not change the set point. The metabolic rate slowed by 500 kcal/day, 6 years after the diet! The Good... Phentermine About 5% loss in total body weight What can we offer Patty? beyond placebo FDA approved (schedule IV controlled) 1. There are more and more patients like Patty and the The Bad... obesity epidemic continues without a plateau in sight. Side effects: dry mouth 2. We have new insights about why diets fail in the long insomnia run. dizzyness hypertension Mechanism: 3. Drug therapy has a modest effect on weight. tachycardia abuse potential stimulant similar to amphetamine 4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard About 50% drop out of therapy from • Safety now better than chole or side effects. • The weight stays off for most – rigorous durability Only indicated for SHORT TERM use • Metabolic surgery more and more accepted The Ugly... Phen-Fen still fresh in everyone’s mind (induced severe pulmonary HTN and/or cardiac valve disease) 10 | [footer text here]

The Good... The Good... Orlistat (Xenical) Rimonabant Over one year, good for about 4-8 pounds over placebo About 5% weight loss beyond placebo May also help with smoking cessation FDA approved for LONG term use The Bad... Reduces DM, HTN The Bad... Side effects: nausea Side effects: depression Mechanism: oily spotting Mechanism: diarrhea staining with flatus pancreatic lipase inhibitor in the GI tract fecal urgency antagonist of cannibinoid receptor CB1 NOT FDA approved steatorrhea Decreases LDL cholesterol The Ugly... Requires daily vitamin ADEK dosing Europe approved, then later withdrew because of suicides (2x risk of psychiatric disorder and 10% The Ugly... depression, 1% suicidal ideation 3x risk of acute kidney injury FDA label: risk of severe liver injury The Good... The Good... Qsymia Lorcaserin (Belviq) About 10% weight loss beyond placebo About 4-8 pounds additional weight loss at 12 weeks beyond placebo FDA approved in 2012 FDA approved in 2012 – Schedule IV Lowers BP. Benefit in sleep apnea. Not a lot of side effects! The Bad... The Bad... Side effects: Side effects: dry mouth hallucinations Mechanism: Mechanism: tingling fingers phentermine: stimulant selective serotonergic agonist 5HT2c constipation topiramate: anticonvulsant Initially declined by FDA over concerns BIRTH DEFECTS about safety. FDA reversed decision in 2012. DEA lists as Schedule IV Initially declined by FDA over concerns narcotic. about suicidal thoughts, palpitations, memory lapses, and cleft lip/palatte The Ugly... The Ugly... Heart valve damage? Need to wait for post marketing studies.... Requires monthly urine pregnancy tests! 11 | [footer text here]

The Good... Bupropion/naltrexone About 12 pounds of weight loss on (Contrave) average. Mechanism: Bupropion: norepinephrine reuptake Less than half of patients achieved inhibitor and nicotinic acetylcholine 5% weight loss at one year. agonist. Activated POMC neurons in hypothalamus = satiety The Bad... Patty Side effects cause ¼ to Naltrexone: opioid antagonist, potentiating effect on the POMC discontinue 262 lbs Some concern about long term cardiovascular effects Costs $100-250 per month! The Ugly... Black box warning: may affect mood and increase risk of suicide Patty Day of We performed an intervention…… intervention 12 | [footer text here]

2 months after 4 months after 208 lbs 180 lbs 6 months after 8 months after 161 lbs 149 lbs 13 | [footer text here]

10 months after 12 months after 146 lbs 143 lbs 18 months after 2 years after 142 lbs 138 lbs …first half-marathon! 14 | [footer text here]

2 year check-up: Weight: 138 pounds BMI 21.6 What was the intervention? Hypertension: resolved. Off all meds. Diabetes: complete resolution. HBA1C 5.6% PCOS: just stopped OCPs, trying to get pregnant Migraines: none in last year Asthma: resolved Stress incontinence: resolved GHRELIN Gastric bypass Cummings, NEJM 2002 15 | [footer text here]