1. OBESITY Bavani Nadeswaran, MD Diplomat American society of Obesity Medicine

2. Which of the following is true about man who is 5'11" tall and weighs 205 pounds? a) There is insufficient information to calculate the BMI, as waist circumference is not included. b) He has a BMI of 25.6 kg/m2 and is overweight. c) He has a BMI of 28.6 kg/m2 and is obese. d) He has a BMI of 31.6 kg/m2 and is overweight. e) He has a BMI of 35.6 kg/m2 and is obese.

3. Which one of the following individuals is considered to be at higher risk for morbidity and mortality related to his or her weight? a) A man with a BMI of 24 and a waist circumference of 104 cm (41 in). b) A woman with a BMI of 26 and a waist circumference of 83 cm (33 in). c) A man with a BMI of 28 and waist circumference of 104 cm (41 in). d) A woman with a BMI of 28 and a waist circumference of 83 cm (33 in). e) A man with a BMI of 28 and a waist circumference of 97 cm (38 in).

4. Evaluation of Obesity

5. History: Comorbid Conditions Diabetes >60% of DMII is obesity related Hypertension Hyperlipidemia CVD and stroke NAFLD/NASH Obstructive sleep apnea/Hypoventilation GERD, hernias Cholelithiasis Cancers DVT, venous stasis Nephrolithiasis Skin conditions Hormonal Hypothyroid, Cushings, PCOS, Hypogonadism, fertility issues Gout Arthritis/Pain Depression Dyssomnia Disordered eating Surgical and treatment complications

7. History: Medications Weight Gain Antidepressants Atypical Antipsychotics PTSD/Sleep Anti-seizure Anti-histamines Anti-hypertensives Insulin, sulfonylureas Steroid Hormones Prednisone, contraceptive  Anti-retrovirals Weight Loss Diet pills, OTC and prescription GLP1 eg Exenatide Metformin Bupropion Topiramate Zonisamide Thyroid hormones Ritalin, amphetamines

8. History: Sleep Sleep Apnea BMI >40, OSA prevalence 40-90% Pain, discomfort Bladder issues Night shiftwork Sleep 8 hrs a/w increased body fat

9. Sedentary Behavior and Obesity TV > 20 hours/week 25% were obese TV < 5 hours/week 11-14% were obese Computer >10 hours/week Increased odds of obesity NOTE: Time spent reading was NOT related to obesity

10. BMI BMI is kg/(m)2 BMI ≥ 25 overweight BMI ≥ 30 obesity BMI 30-34.9 Class 1 BMI 35-39.9 Class 2 BMI ≥ 40 Class 3 or morbid/excessive obesity  Does NOT include: Gender, Age, Race, Body Composition, Fat distribution

11. Utilization of BMI Risk Assessment: E.g. For every 1 point increase in their BMI above 25, women had a 12% lower chance of surviving to age 70 in “good health”. Similar trends found in men. BMJ medical journal, U.S National Institutes of Health Boston Obesity Nutrition Research. Definition: Overweight and obesity, class I, II, II obesity Categorize: Bariatric surgery BMI ≥ 35 with comorbid or ≥40 with no additional comorbid conditions Diet pills BMI≥ 27

12. Abdominal Obesity Waist Circumferance > 102 cm (40”) in men >88 cm (35”) in women Waist : Hip >1:1 in Men >0.8 in women BMI & Waist Circumference = 2 pivotal factors in metabolic risk (NHLBI)

13. Obstructive Sleep Apnea Evaluation Neck Circumference >17” (M) and >16” (F) associate with Sleep Apnea Mallampati Score

14. Physical Assessment: Underlying Syndromes Diabetes: acanthosis nigricans/skin tags, polys, A1c, glucose Cushings: striae, thin skin, moon facies, ‘buffalo hump’, thin extremies with central obesity, ↑glucose, cortisol labs Hypogonadism: gynecomastic, fatigue, low vitality and libido, hormonal labs Hypothyroid: tired, dry skin, goiter, hyporeflexive, TSH lab Sleep apnea: neck size, pharynx, htn, dysrhythmia, snoring, cognitive decline, MVA’s, sleep study PCOS: hirsutism, acne, fertility or dysmenorrhea issues, hormonal labs, vag ultrasound

15. Physical Assessment: Lab Medical Weight Loss Glucose, A1c BUN, Cr, Lytes Liver profile Lipid profile C-reactive protein Uric acid CBC TSH Urine Nutritional prn Surgical Weight Loss Medical labs Iron, ferritin B12, RBC folate, B1 (thiamine) Ion calcium, iPTH Nutritional prn

16. A 54 year old woman with BMI of 31 kg/m2 presents for a physical exam. Which of the following is most appropriate initial recommendation for weight loss ? a)Recommend weight loss of 20% of current weight in 6 months, or 4-5 pound weight reduction/week. b) Assess previous attempts at weight loss before recommending an option. c) Reduction of caloric intake below 1000 kcal/day for a month to jumpstart her weight loss. d) Refer for bariatric surgery consultation.

17. A 47 year old man is seeking advice on diets. Which of the following is the most appropriate recommendation? a) Maintain caloric intake from fat to below 15% of total calories. b) Commercial diets such as Weight Watchers have not been studied in clinical trials; therefore they are not recommended. c) When comparing diets of very low-carbohydrate (Atkins) to very low-fat (Ornish), the rates of weight loss are the same at 6 months and 1 year. d) When comparing diets of very low-carbohydrate (Atkins) to very low-fat (Ornish), the average weight loss in one year was 7-10 kg greater on Atkins. e) When comparing diets with varying percentages of fat, protein, and carbohydrates, the average weight loss was the same at 2 years.

18. For a patient seeking counseling prior to starting an exercise program, which of the following is the most appropriate advice? a)Exercise alone (without dietary changes) typically results in significant weight loss of about 3-5 kg/week. b) Exercise-induced weight loss is less effective in reducing total body fat than diet-induced weight loss. c) Evidence supports screening asymptomatic men >45 yrs and women >55 yrs with an exercise stress test prior to starting a vigorous exercise program. d) Exercise has been shown to result in significant weight loss, but it is not as important for weight maintenance. e) Lifestyle activities, such as housework or parking the car further from the store, can achieve important health benefits

19. A 52 year old woman is ready to embark on a program to lose weight through caloric restriction and moderate physical activity. Which ONE of the following is true about behavioral techniques for weight loss? a)Keeping a food diary is the most effective behavioral strategy for inducing weight loss. b) Psychotherapy is an effective method of losing weight for most people. c) Group weight loss classes (i.e. education with social support) are not as effective as individual counseling. d) Time management is the most effective behavioral strategy for inducing weight loss. e) Behavioral strategies play only a small role in losing weight.

20. 10% Weight Loss Will Beneficially Improve the Following Conditions Affected by Obesity: Osteoarthritis Rheumatoid Arthritis Cancers of Breast, Esophagus, Stomach, Colon, Endometrium & Kidney CAD Carpal Tunnel Syndrome Chronic Venous Insufficiency Daytime Somnolence DVT DMII Kidney Disease Gall Bladder Disease Gout Heart Disorders HTN Impaired Immunity Impaired Respiratory Function Infection Following Wounds Infertility Liver Disease Low Back Pain OBGYN Complications Pain Pancreatitis Sleep Apnea Stroke Surgical Complications Urinary Stress Incontinence

21. DIET

22. Caloric Value of Food Proteins: 4 Cal Carbohydrates: 4 Cal Fats: 9 Cal Alcohol: 7 Cal

23. Dietary Therapies Can Be Focused on ENERGY DENSITY Energy density is the amount of energy available for a given weight (kcal/grams) Low energy density foods such as fruits and vegetables are emphasized High energy density foods (high fat foods) are reduced Eating lower densities allows for eating a greater weight of food, and this leads to satiety

24. The Glycemic Index Measurement of the elevation of blood glucose that occurs after the ingestion of a single carbohydrate food. Foods with a lower glycemic index are absorbed more slowly and may be preferable for obese individuals especially if they have insulin resistance. Measurement of the glycemic index is controversial and complicated as it is affected by the form of the food and by other foods eaten along with that particular one. Glycemic Load takes quantity into consideration.

25. Dietary Strategies Calorie Restricted / Balanced Deficit Diets Macronutrient-Specific Diets: - Low fat diet - Low carbohydrate diet (carbohydrate restriction) Protein-Sparing Modified Fast/Very Low Calorie Diet Meal Replacements Diets Post-Bariatric Surgery

26. Classification of Diets by Calories 0 – 400 Starvation; never recommended 400 – 800 VLCD (Very Low Calorie Diet) 800 – 1500 LCD (Low Calorie Diet) Above 1500 BDD (Balanced Deficit Diets) - Reduction of 500 – 1000 kcal/d from - Commercial programs- Jenny Craig, Weight watchers Self directed programs Atkins, Ornish, South Beach, Weight Watchers, Zone

27. VLCD Efficacy and Typical Weight Loss Losses of 15 – 22 pounds in 4 weeks Losses of 44 pounds in 12 weeks Losses of 68 – 90 pounds in 19 – 20 weeks By contrast, only 5 – 10% of patients lose 44 pounds or more with more conservative therapies

28. Low Calorie Diets (LCD) Calorie intake typically from 800 – 1500 cal/day Many different types: Calorie-reduced/balanced-deficit: focuses on counting calories or an exchange system of points Portion-controlled: the use of some meal replacements Low-fat: counting fat grams to reduce calories Low-carb: carbohydrate restriction leads to appetite reduction

29. Meal Replacement Diets Can be used as a complete diet program or as meal substitutes for 1 or 2 meals Have been shown be successful Used successfully in the “Action for Health in Diabetes” Program (AHEAD) In the first year exercise, attendance at treatment session, and use of meal replacements showed the highest correlation with weight reduction

30. Examples of Diet Programs DASH: Dietary Approaches to Stop Hypertension A balanced diet with no extreme percentages of macronutrients; low in sugar, salt, alcohol and saturated fat The Zone Diet: 40% C, 30% P, 30% F; focuses on lean meats (especially poultry), avoids high-fat animal products South Beach Diet: 28% C, 33%P, 39% F; emphasizes healthy carbs, such as whole grains and certain fruits and vegetables; Atkins Diet: 6% C, 35% P, 59% F; severe carbohydrate restriction and a high-fat diet Mediterranean Diet: 40% C, 17% P, 43% F; high amount of mono- unsaturated fats. The diet contains: vegetables, fruits, cereals, dairy products, meats and poultry, fish, wine, legumes, and olive oil – in that order American Diabetes Association (ADA): 60% C, 20% P, 20% F; Based on “exchange units”. For a 1600 calorie diet, it includes: 9 starch, 4 fruit, 4 vegetable, 5 meat, 2 milk, and 6 fat exchanges

32. Lean Body Mass Protection Extreme hypocaloric states increase protein requirements above recommended levels As a rule, on 800-1200 C LCD, use 1 gram of protein per kg IBW/d (65-70 gm/d) Over 1200, use 1 – 1.5 gram of protein per kg of IBW/d Typical weight loss has been shown to be 75% fat and 25% lean body mass

33. Physical Activity and Obesity

34. Energy Expenditure

36. Adaptations in CV Function and Aerobic Physical Activity ↑ Total Blood Volume ↑ Ventricular Compliance ↑ Venous Return ↑ Myocardial Contractility ↑ End Diastolic Vol ↑ Ejection Fraction ↑ Stroke Volume ↑ Cardiac Output ↑ Effectiveness of Cardiac Output distribution Optimized Peripheral Blood Flow ↑ Blood Flow to Active Muscle Decreased Resting HR

37. MET = Metabolic Equivalent What is a MET? An expression of energy cost in reference to physical activity  1 MET = resting O2 Consumption = 3.5ml/kg/min = sitting quietly  2 MET = twice RMR Estimates energy expenditure or cost of a particular activity

38. MET Categories  Light < 3 METs Driving your automobile = 2  Moderate = 3-6 METs Walking 4 mph, brisk pace = 5  Vigorous > 6 METs Carrying 25-49pds upstairs = 8

39. Exercise Dose-Response Curve

40. How Much Physical Activity Is Enough? General Health Benefit Moderate aerobic exercise 150 min/wk (about 30 minutes 5x/wk) + strength training Active Weight Loss 150-250 minutes per week Prevention of Weight Regain 300-420 minutes per week

41. Basic Physical Activity Rx: FITTE  Frequency  Intensity  Time  Type  Enjoyment

42. Behavioral Therapy

43. CBT Common Techniques Plan strategies—avoid food and situational triggers (Forget the pizza!) Substitute—food for another or non-food Planning—Prepare for special events Food Diary—Reminder, learning tool, feedback, journaling Create structure—specific time and place to eat, avoid mindless eating, how to shop

44. Lifestyle Change Counseling Strategies Realistic goals–Set moderate short-term goals Make small increases in daily walking Decrease portion size Feel good about yourself and your success Self-monitoring –If doctors could counsel on one behavioral strategy it is self monitoring Raising self-awareness is absolutely necessary Patients underestimate calories by 1/3 Overestimate physical activity by 1/2 Journaling is important

45. The Spirit of Motivational Interviewing (MI) Emphasizes personal choice and control Collaborative: partnership between patient and clinician Evocative: reasons to change come from patient rather than doctor Honoring patient autonomy: ultimately the patient decides what to do

46. Eating Attitudes and Behavior Assessments  Binge Eating DO - Binges 2 times/week for 6 months, no compensatory behavior  Night Eating DO - Consume 25-50% daily calories after evening meal  Anorexia – distorted body image, fear of gaining weight, missed periods  Bulemia - Binges at least 2 times/week for 3 consecutive months, followed by purging

47. For which of the following patients would the addition of pharmacotherapy for weight loss be appropriate, after attempts at lifestyle modification and caloric restriction have proven unsuccessful? a) A 25 year-old woman with impaired glucose tolerance and a BMI of 25 kg/m2. b) A 33 year-old man with hypertension and a BMI of 26 kg/m2. c) A 30 year-old woman with knee osteoarthritis and a BMI of 26 kg/m2. d) A 50 year-old man with normal blood pressure and glucose and a BMI of 31 kg/m2.

48. PHARMACOTHAY

49. Phenylethylamines Sympathomimetic effect – release norepinephrine from synaptic granules Works at level of central nervous system – hypothalamus and limbic system Appetite suppressant effect – anorectic Exact mechanism(s) for weight loss unknown Improvement of leptin sensitivity Effect on thermogenesis and BMR

50. Indications: Short term adjunct in a regimen of weight reduction involving lifestyle changes in the management of adult exogenous obesity BMI > 30 or > 27 with comorbidities (HTN, DM, hyperlipidemia) Contraindications: -advanced arteriosclerosis, CAD, mod/severe HTN, hyperthyroid, glaucoma, agitated states, history of known drug abuse, pregnancy Phenylethylamines – FDA labeling

51. Phenylethylamines - Studies Sympathomimetic + longitudinal care ASBP guidelines. Observational cohort 11,000 patients followed up to 5 yrs. Weight loss 10.2% initial body weight – 6 M Weight loss 10.65% initial body weight – 1 Y Weight loss 5% initial body weight – 5 Y

52. Orlistat Common names: Xenical®, Alli® Doses: Xenical – 120 mg tid with meal or <30 min post Alli – 60 mg tid with meal

53. Orlistat - Mechanism Gastric and Pancreatic lipase inhibitor Inhibits uptake of up to 1/3 of ingested fat ½ life of 1-2 hours Needs to be used in accordance with low-fat, calorie controlled diet

54. Orlistat - Studies RCT of 800 primary care patients – 17 centers; orlistat vs usual care over 2 years Average WT loss 8 kg vs 4 kg for placebo 57% of orlistat patient lost 5% of initial body WT at year 1 vs 30% placebo (dose dependent) 44% of orlistat maintained 5% of initial WT loss at year 2 vs 24% placebo

55. Topiramate Mechanism of action in weight loss: unknown Increased satiety through reduced GI motility Increased taste aversion Reduced calorie intake

56. Topiramate - Studies Weight loss maintenance RCT 300 subjects lost 8% initial body weight in 8- week diet run-in period; followed 44 week after Placebo gained 1.8% 96 mg lost 5.2% more 192 mg lost 6.4% more

57. Topiramate - Pragmatic Topiramate may be used off-label for the treatment of Obesity Synergistic effect when used along with phentermine Consider it over weight + counterparts (B-blockers, TCA’s) for migraine prophylaxis (FDA approved use) Parasthesias are relatively common but self-limited when come off drug Monitor bicarb levels routinely

58. Qsymia Qsymia (Phentermine/topiramate) Dosing regimen: 3.75/23 mg; 7.5/46 mg; 11.25/69 mg; 15/92 mg Two - 1 yr long RCT’s demonstrate 7.5 % and 9.5% additional WT loss over placebo (CONQUER) FDA apporved: treatment of obesity BMI >30 or BMI >27 with at least one obesity related comorbidity Contraindic: pregnancy, glaucoma, hyperthyroidism

59. Lorcacerin (Belviq®) Common name: Belviq® Doses: 10 mg po bid Mechanism: Serotonin 3C receptor agonist (fenfluramine was primarily at 2B receptor agonist) FDA approved: Weight loss Clinical trials: 3 RCT’s 1-2 years in length – 6000(n) Weight loss 1 year: 7.3 kg vs. 3.7 (control) Weight loss 2 year: 6.0 kg vs. 2.6 (control )

60. Lorcacerin (Belviq®) Common SE: headache, dizziness, GI changes (nausea) Rare SE: serotonin syndrome, valvular heart defects, priapism “If using lorcacerin concomitantly with another serotonin agent use extreme caution and careful observation.” “...2.4% of Belviq and 2.0% of patients receiving placebo developed echocardiographic criteria for valvular regurgitation at year one.” Particular caution in CHF patients

61. Metformin  Metformin (Glucaphage, Glucaphage XR):  Doses (500 or 850 bid/tid with meals)  Does come in an extended release from  Biguanide: reduces hepatic glucose production and improves insulin sensitivity  Induces modest weight loss initially.  Improves fertility in PCOD patients.  Reduces insulin resistance and may have a role in DM prevention

62. Metformin - Studies  Many studies pointing to utility of metformin in DM treatment, prevention, and weight loss  RCT weight loss study 12 diet treated NIDDM obese women over 24 weeks  1700 mg had significant reduction in appetite and calorie intake vs placebo over study period  Lost 8 kg more weight over 24 weeks than placebo

63. GLP-1 Agonists  Common names: Byetta (exenatide), Victoza (liraglutide)  Approved for treatment for type 2 DM  Liraglutide treatment for diabetes: Begin 0.6 mg SQ qd for 1 wk Then to 1.2 mg SQ qd (max dose of 1.8 mg qd)  Exenatide treatment for diabetes: Begin 5 mcg bid 30-60 min prior to meals for 1 M Then to 10 mcg bid 30-60 min prior to meals

64. GLP-1 Agonists - Mechanism  Enhance glucose dependent insulin release  Suppress inappropriate glucagon release  Delays gastric emptying  Reduction in food intake directly acting on receptors in the hypothalamus and area postrema

65. GLP-1 Agonists - Pragmatic  Great medications for DM treatment and for weight loss  Works synergistically with carbohydrate controlled dieting  Nausea is fairly common but usually self-limited which is reason for titration schedule  Be mindful of acute back pain or vomiting – D/C med and check pancreatic enzymes

66. Bupropion  Brand name: Wellbutrin, Wellbutrin XL, Zyban  Dosing: begin 150 qd for three days then titrate to 150 mg bid (or 300 mg qd for XL form)  Mechanism: Dopamine and norepinephrine reuptake inhibitor  FDA approved: major depressive disorder, smoking cessation  Caution: may lower seizure threshold, do not use in bulimia patients

67. Bupropion - Pragmatic  Very good antidepressant for depression with sedentary component. May at times worsen anxiety  Works centrally as an appetite suppressant (similar chemical structure as diethylpropion)  Only anti-depressant with consistent weight loss effect  May help blunt weight regain in smoking cessation

68. Mr. S. is a 45 year old man with a BMI of 49 kg/m2 type 2 diabetes, hypercholesterolemia and obstructive sleep apnea who has been unable to lose weight despite multiple attempts over the past 4-5 years. He is concerned about his long-term health and is considering bariatric surgery. Which of the following statements about bariatric surgery is true? a) Patients who undergo bariatric surgery require close follow-up for the first 2 years, but then can resume normal medical care and follow-up after that. b) The most commonly performed surgery in the U.S. is the Roux-en-Y gastric bypass, a procedure which combines both restriction and malabsorption to achieve weight loss. c) Like lifestyle modification and pharmacotherapy for obesity, there is no data on the long-term benefits of bariatric surgery. d) If he undergoes adjustable banding surgery, he can expect to achieve a near normal BMI within 5 years.

69. A 44-year-old man status post gastric bypass 4 months prior to admission presented with 2 weeks of numbness and weakness in his lower extremities requiring him to use a walker at home to ambulate. He also noted vomiting 2-3 times per day since his bypass. Neurologic exam revealed normal strength in the upper extremities; decreased strength bilaterally in the knee flexors, decreased pin-prick, 2-point discrimination, deep tendon reflexes, and temperature sensation in both lower extremities; as well as unsteady gait. What test are you going to order? 1.MRI spine 2.Electromyography 3.CBC with Diff and LP 4.Vitamin B 12 level 5.Vitamin B1 level

70. Why “Do” Weight Loss Surgery?  Because it works!  When weight is lost comorbidities improve.  Across the range of medical problems, about 90% of them will either improve or resolve.  Long term mortality is reduced.

71. Mortality Reduction  The August 23rd 2007 edition of New England Journal of Medicine provided breakthrough  Sjostrom et al in the Swedish Obesity Study (SOS) show a 29% reduction in death at average follow-up of 10.9 years  Adams et al in a retrospective study of 7900 patients at 7.1 years, 40% reduction in mortality; 60% in cancer death; 92% in DM death

72. Who is a Candidate for WLS?  NIH 1991 guidelines  Patients with a BMI of 40 or greater (roughly 100 pounds overweight)  Patients with a BMI of 35 (roughly 80 pounds overweight) or greater who also suffer from a severe medical condition related to obesity (sleep apnea, diabetes, HTN, etc…)  A patient who is prepared and willing to commit to the lifestyle changes that will be necessary after surgery.

73. Who has Increased Risk for WLS?  Male sex  Age >45  Diabetes and Hypertension  BMI > 50  Sleep apnea  History of thromboembolic events  History of unstable angina or CHF  Smokers

74. Types of Surgery  Purely Restrictive Restricts the amount of food (less calories). Does not alter digestive function Ex: Laparoscopic Adjustable Gastric Band (LAGB), Sleeve Gastrectomy  Mostly Restrictive Majority of WL by restriction (small stomach pouch) Smaller component by limiting calorie absorption. Ex: Gastric Bypass  Mostly Malabsorptive Larger percentage of small bowel “bypassed” leading to less absorption of ingested food (esp fat) Examples: Duodenal Switch, Biliopancreatic Diversion, or “long limb” Gastric Bypass Much less commonly done

75. Gastric Bypass  Rapid initial weight loss  Most done laparoscopically  Mainly restrictive; a little malabsorptive  Longer experience in USA  Most common WLS in the USA  Surgery: 1 hour and 40 minutes  Hospital stay: 1-3 days  Full recovery: 4-6 weeks

76. Laparoscopic Adjustable Gastric Banding  Band is placed around the top of the stomach  Induces weight loss three ways: Creates a small “stomach pouch” that fills with a little food. “Squeezes” the stomach prolonging the sensation of fullness. Helps suppress appetite.

77. Laparoscopic Sleeve Gastrectomy  Removes the “greater curve” (stretchy part)  Nothing is bypassed so there is very little malabsorption  Anatomy remains normal  Stomach is much smaller - about the size/shape of medium banana  Ghrelin decreases so hunger decreases  Increasingly popular and fastest growing option

78. Mostly Malabsorptive Procedures

79. Weight Loss Results  LAGB - ave. best WL = 45-50% EBW; 30 Kg Longterm - 40% regain most of their weight  Gastric Bypass - ave. best WL = 65-70% EBW; 40 Kg Longterm - 20% regain most of their weight  Sleeve Gastrectomy - ave. best WL=60-70% EBW; 37 Kg Longterm – unknown  Malabsorptive Procedures - ave. best WL=75-85%; 53 Kg Longterm- unknown