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Management Of The Morbidly Obese

This document summarizes the management of morbid obesity. It defines obesity as an energy imbalance, classifies obesity by BMI, examines the genetic and environmental origins of obesity, discusses current treatment options including diet, pharmaceuticals, and bariatric surgery, and explores the effects and prevalence of obesity.

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Overview of obesity management objectives, including origins, treatments, effects of bariatric surgery.

Definition of obesity, classification by BMI, and historical context as a mortality marker.

Statistics on overweight and obesity in the U.S., its preventable death toll, and related diseases.

Discussion on obesity's genetic and environmental origins, including energy balance regulation.

Current treatment methods including diet, pharmaceuticals, and surgical interventions.

Detailed analysis of obesity medications like Sibutramine, Bupropion, Orlistat, including MOA and clinical trials.

Bariatric surgery types and outcomes, highlighting gastric bypass and banding procedures.

Comparison of gastric banding vs bypass outcomes; focuses on weight loss and complications.

Potential complications of bariatric surgery, including short bowel syndrome and surgical risks.

Effects of bariatric surgery on co-morbidities and overall health improvements post-surgery.

Key considerations in obesity treatment, stressing the rising prevalence, genetic factors, and efficacy of surgery.

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Management of the Morbidly Obese Sarah Nelson, Pharm.D. Pharmacy Practice Resident
Objectives Describe the proposed origins of obesity Discriminate between current treatment options for obesity Examine the effects following bariatric surgery Distinguish dynamic and kinetic differences in obese patients
Definition of Obesity An imbalance between energy intake and energy expenditure Consumption of calories which exceeds that required for the resting metabolic rate and active energy expenditure Energy equation: Intake (food) = expenditure + storage Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
Classification of Body Weight Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737 Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6 th edition. 63-81. Class III Obesity ≥ 40 Class II Obesity 35.0-39.9 Class I Obesity 30.0-34.9 Overweight 25.0-29.9 Normal weight 18.5-24.9 Underweight <18.5 Weight Category BMI (kg/m 2 )
Background Obesity recognized as a marker for mortality in the 1960’s Analysis of life insurance redemption Mortality lowest when BMI 20-25 Mortality dramatically increased when BMI >35 Mortality also increased when BMI <20 In 2000, WHO declared obesity as the greatest health threat facing the West Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
Prevalence of Weight Disorders 1.6 billion individuals are overweight Highest in United States 2 out of 3 Americans are overweight ½ of all overweight Americans are obese BMI ≥ 35 kg/m 2 : 23 million Americans BMI ≥ 40 kg/m 2 : 8 million Americans Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
Effects of Weight Disorders Major cause of preventable death >100,000 deaths per year $70 billion health care dollars per year 10% of national healthcare expenditure Pieracci F, Barie P, Pomp A. Critical care of the bariatric patient. Crit Care Med. 2006;34: 1796-1804
In a Decade . . . http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm
Effects of Obesity Increase in prevalence of co-morbidities Diabetes Mellitus Type 2 Heart Disease (HTN, XOL, stroke) Obstructive sleep apnea Weight-bearing degenerative disorders Depression Cancer Decreased life expectancy Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
Obesity and Diabetes Increase in circulating free fatty acids competes with circulating glucose  elevated insulin secretion and resistance Resistin, adiponectin, and TNF- α interact with insulin to generate insulin resistance Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S. http://www.nature.com/nrm/journal/v9/n5/images/nrm2391-f2.jpg
Origins of Obesity
Origins of Obesity Genetic Environmental/Behavioral
Regulation of Energy Balance Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
Genetic Effects Gene deletions/mutations Leptin deficiency/leptin receptor modification MC4R deficiency Most common monogenic disorder to date Present in 1-6% of obese individuals GAD65 over-expression Increases production of GABA  increased food intake Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
Genetic Effects Syndromic association >20 syndromes caused by genetic defects or chromosome abnormalities are characterized by obesity Most are in the setting of mental retardation Prader-Willi syndrome Pseudohypoparathyroidism type 1A Bardet-Biedl syndrome Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
Genetic Effects Genetics of common obesity 1977 NHLBI Twin Study  familial obesity due to genetic factors rather than environment Estimated heritability value of 0.81 upon 25 year follow up Adoption Studies Adopted children have body sizes more similar to biologic parents rather than adopted parents Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29. Stunkard A, Sorenson T, Hanis C, et al. An adoption study of human obesity. JAMA. 1986;314:193-198.
Environmental Location Access to walk paths, recreational facilities, etc. Access to fast food restaurants, supermarkets, health-related stores Socioeconomic status (SES) Inverse relationship between individual and area-level SES and weight Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
Environmental Results from the Ontario Heart Health Surveys (OHHS) demonstrate an increase in obesity with: Increased age (females>males) Absence of high school education Adoption of a sedentary lifestyle Nicotine consumption was a negative risk factor for obesity in the OHHS population Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
Treatment Options for Obesity
Treatment Options for Obesity Diet Therapy Pharmaceutical Agents Sibutramine Orlistat Bupropion Potential targets Surgical Therapy Gastric Banding Gastric Bypass Biliopancreatic diversion
Sibutramine (Meridia ® ) MOA: inhibits norepinephrine (NE) and serotonin (5-HT 2 ) neuronal uptake  enhances satiety Dose: 10 mg PO once daily x 4 wks, then may  to 15 mg daily x 100 wks Adverse Effects (>10%) Headache Insomnia Xerostomia Constipation Chaput JP, Tremblay A. Current and novel approaches to the drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
Sibutramine (Meridia ® ) Bray et al. (1999) Bray G, Blackburn G, Ferguson J et al. Sibutramine produces dose-related weight loss. Obes Res. 1999;7:189-98 . 46.5* 77.2* 9.0 30 101 36.5* 71.9* 8.2 20 96 34.7* 67.3* 7.0 15 98 17.2* 59.6* 5.7 10 99 12.1* 37.4 Ұ 3.7 5 107 10.5 Ұ 25.3 2.4 1 95 0 19.5 1.3 Placebo 87 >10% wt loss (%) >5% wt loss (%) Mean wt reduction (kg) Dose (mg) n
STORM Trial Randomized, double-blind, placebo controlled trial Effect of weight maintenance after weight loss All patients on a 600 kcal/day deficit diet James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
STORM Trial James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
Sibutramine (Meridia ® ) Use with caution in patients on concurrent serotonergic medications  risk of serotonin syndrome Previous black box warning Use with caution in patients with uncontrolled hypertension 12.5% patients   in BP by 15 mmHg Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
Bupropion MOA: inhibits NE and DA neuronal uptake  enhances satiety Dose: 300 to 400 mg daily Non-FDA approved indication Contraindicated in patients with seizure disorders Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
Bupropion Anderson et al. (2002) 24 week RDBPC parallel-group study Compared placebo, 300 mg, & 400 mg daily Calorie restricted diet & lifestyle intervention program initiated Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
Bupropion Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
Orlistat (Alli ® , Xenical ® ) MOA: reversible inhibitor of gastric and pancreatic lipases  decreases dietary fat absorption Only FDA approved drug that directly alters metabolism Dose: 120 mg TID with meals
Davidson et al. (1999) 2-year DBRPC study Diet modified to ensure adequate fat intake Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
Concerns with orlistat:  in fat-soluble vitamin deficiency Gastrointestinal adverse effects common Fatty/oily stool (20%) Oily spotting (26.6%) Fecal incontinence (7.7%) Fecal urgency (22.1%) Flatulence with discharge (23.9%) Orlistat (Alli®, Xenical®) Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
Other Medications Metformin 1700 mg daily  300 kcal intake reduction/30-minute eating period  hunger ratings Topiramate 65.2% of patients had weight loss of 0.5 kg to 19.5 kg in migraine study 200 mg daily  average body weight  5.9 kg Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
Future Pharmacologic Agents Recombinant human leptin Neuropeptide Y antagonists GLP-1 Ghrelin antagonists Endocannabinoid receptor antagonists Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
Rimonabant MOA: CB 1 receptor antagonist Dose: 20 mg daily Adverse Effects: suicidal ideation, anxiety, depression Not available in US NDA withdrawn
RIO Trials Efficacy Decreased body weight (-6.6 kg) Decreased waist circumference (-3.9 cm) Decreased BP (-1.8 mmHg SBP) Decreased A1c (0.7%) No decrease in LDL, total cholesterol Safety RR 1.9 for any psychiatric disorder 2.5x more likely to discontinue medication due to depression Idelevich E, Kirch W, Schlinder C. Current pharmacotherapeutic concepts for the treatment of obesity in adults. Therapeutic Advances in Cardiovascular disease. 2009;3:75-90.
Leptin Peptide that acts on the hypothalamus to modulate body weight, intake and fat stores Leptin deficiency  early onset obesity Treatment options: Leptin analogues > native leptin Leptin gene promoters CNTF may also potentiate leptin-like effects Chaput J, Tremblay A. Current and novel approaches to drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
Bariatric Surgery Only option for treatment of morbidly obese 20-fold increase in procedures in last 10 years Types of surgery Restrictive Malabsorptive Combination Steinbrook R. Surgery for severe obesity. NEJM. 2004;350:1075-79. Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.
Gastric Bypass Restrictive and malabsorptive Causes early satiety and incomplete nutrient digestion and absorption Roux-en-Y surgery Creation of 15-30 cm gastric pouch Connection of jejunum to gastric curvature Bypasses portion of stomach, duodenum, and portion of jejunum Most common bariatric surgery Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
Gastric Bypass Complications Mortality rate: 0.5% Early complications: anastomotic leak, PE, infection Late complications: strictures, bowel obstruction, malnutrition, dumping syndrome Outcomes 62-68% excess weight loss at 2 years Initial weight loss of 70-80% excess weight Regain of weight after 2 years is common Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
Gastric Banding Restrictive procedure Implantation of inflatable silicone band around the upper stomach Band adjustments are based on individual weight loss and appetite Adjustments required 5-6 times in 1 st year Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
Gastric Banding Complications Safest bariatric procedure available Mortality rate: 0.05-0.1% Late complications: gastric prolapse, band erosion, port infection, tubing problems Outcomes Weight loss is gradual 57% excess weight loss after 6 years Direct correlation with motivation and follow-up Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
Banding vs. Bypass Tice J, Karliner L, Walsh J et al. Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures. The American Journal of Medicine. 2008;121:885-93. 14 17 Long term complication 3.3 5.2 Short term complication 75 84 Osteoarthritis 48 37 Dyslipidemia 66 56 Hypertension 72 77 Diabetes 64 34 Weight loss Gastric Bypass (n=232) Gastric Banding (n=160) Pt characteristic (%)
Biliopancreatic diversion Restrictive and malabsorptive properties Limited gastrectomy Roux-en-Y reconstruction Patient still allowed to eat a full meal Results similar initially to gastric bypass Continued malabsorption increases 2 nd year weight loss Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Matrusso A, Roslin M, Kurian M et al. Bariatric surgery: an overview of obesity surgery. 2006;119:1357-62.
Complications of Bariatric Surgery Unexpected reoperation Wound dehiscence Foreign body removal laparotomy Splenic injury Hemorrhagic Intra-op hemorrhage Post-op hematoma Blood transfusion Anastomotic Leak Abdominal drainage Wound Infection Seroma dehiscence Obstruction Small bowel obstruction Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
Short Bowel Syndrome (SBS) Definition: intestinal remnant <180 cm AND malabsorption Complications necessitate small bowel resection Bowel obstruction Internal hernias Mesenteric thrombosis In a review of 265 pts with SBS 15% due to bariatric surgery 82% had Roux-en-Y gastric bypass McBride C, Petersen A, Sudan D. Short bowel syndrome following bariatric surgical procedures. American Journal of Surgery. 2006;192:828-32.
Outcomes in the Bariatric Patient
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -46.3 Biliopancreatic diversion -28.6 Gastric banding -43.5 Gastric bypass -8.6 Bupropion -7.6 Orilstat -10.2 Sibutramine Absolute weight change (kg) Treatment
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. --- Biliopancreatic diversion --- Gastric banding --- Gastric bypass -1.73 Bupropion -0.8 Orilstat 0.1 Sibutramine Systolic BP (mmHg) Treatment
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -5.79 Biliopancreatic diversion -3.2 Gastric banding -3.4 Gastric bypass -2.71 Bupropion 1.0 Orilstat -0.8 Sibutramine Fasting glucose (mg/dL) Treatment
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. Biliopancreatic diversion Gastric banding Gastric bypass -2.95 Bupropion -20 Orilstat -0.8 Sibutramine LDL (mg/dL) Treatment
Results from Bariatric Surgery Co-morbidities resolve as weight ↓ Hospitalization rate increases Band adjustments Complications Complications exist Nutritional deficiencies Medication absorption issues Surgical complications Short bowel syndrome Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
In the mean time . . .
Dosing Controversies in Obesity Weight IBW vs. ABW vs. Adjusted body weight Distribution Lipophilic vs. hydrophilic Protein bound Clearance Absorption Following bariatric surgery Erstad B. Which weight for weight-based dosage regimens in obese patients? AJHP. 2002;59:2105-10.
Conclusions Obesity is becoming more prevalent Genetic make-up may predispose pts to obesity Pharmacological agents + diet are effective for overweight patients Bariatric surgery is recommended for pts with BMI>35 Bariatric surgery is most effective treatment for obesity

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Management Of The Morbidly Obese

  • 1.
    Management of theMorbidly Obese Sarah Nelson, Pharm.D. Pharmacy Practice Resident
  • 2.
    Objectives Describe theproposed origins of obesity Discriminate between current treatment options for obesity Examine the effects following bariatric surgery Distinguish dynamic and kinetic differences in obese patients
  • 3.
    Definition of ObesityAn imbalance between energy intake and energy expenditure Consumption of calories which exceeds that required for the resting metabolic rate and active energy expenditure Energy equation: Intake (food) = expenditure + storage Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
  • 4.
    Classification of BodyWeight Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737 Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6 th edition. 63-81. Class III Obesity ≥ 40 Class II Obesity 35.0-39.9 Class I Obesity 30.0-34.9 Overweight 25.0-29.9 Normal weight 18.5-24.9 Underweight <18.5 Weight Category BMI (kg/m 2 )
  • 5.
    Background Obesity recognizedas a marker for mortality in the 1960’s Analysis of life insurance redemption Mortality lowest when BMI 20-25 Mortality dramatically increased when BMI >35 Mortality also increased when BMI <20 In 2000, WHO declared obesity as the greatest health threat facing the West Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
  • 6.
    Prevalence of WeightDisorders 1.6 billion individuals are overweight Highest in United States 2 out of 3 Americans are overweight ½ of all overweight Americans are obese BMI ≥ 35 kg/m 2 : 23 million Americans BMI ≥ 40 kg/m 2 : 8 million Americans Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
  • 7.
    Effects of WeightDisorders Major cause of preventable death >100,000 deaths per year $70 billion health care dollars per year 10% of national healthcare expenditure Pieracci F, Barie P, Pomp A. Critical care of the bariatric patient. Crit Care Med. 2006;34: 1796-1804
  • 8.
    In a Decade. . . http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm
  • 9.
    Effects of ObesityIncrease in prevalence of co-morbidities Diabetes Mellitus Type 2 Heart Disease (HTN, XOL, stroke) Obstructive sleep apnea Weight-bearing degenerative disorders Depression Cancer Decreased life expectancy Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
  • 10.
    Obesity and DiabetesIncrease in circulating free fatty acids competes with circulating glucose  elevated insulin secretion and resistance Resistin, adiponectin, and TNF- α interact with insulin to generate insulin resistance Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S. http://www.nature.com/nrm/journal/v9/n5/images/nrm2391-f2.jpg
  • 11.
  • 12.
    Origins of ObesityGenetic Environmental/Behavioral
  • 13.
    Regulation of EnergyBalance Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  • 14.
    Genetic Effects Genedeletions/mutations Leptin deficiency/leptin receptor modification MC4R deficiency Most common monogenic disorder to date Present in 1-6% of obese individuals GAD65 over-expression Increases production of GABA  increased food intake Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  • 15.
    Genetic Effects Syndromicassociation >20 syndromes caused by genetic defects or chromosome abnormalities are characterized by obesity Most are in the setting of mental retardation Prader-Willi syndrome Pseudohypoparathyroidism type 1A Bardet-Biedl syndrome Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  • 16.
    Genetic Effects Geneticsof common obesity 1977 NHLBI Twin Study  familial obesity due to genetic factors rather than environment Estimated heritability value of 0.81 upon 25 year follow up Adoption Studies Adopted children have body sizes more similar to biologic parents rather than adopted parents Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29. Stunkard A, Sorenson T, Hanis C, et al. An adoption study of human obesity. JAMA. 1986;314:193-198.
  • 17.
    Environmental Location Accessto walk paths, recreational facilities, etc. Access to fast food restaurants, supermarkets, health-related stores Socioeconomic status (SES) Inverse relationship between individual and area-level SES and weight Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
  • 18.
    Environmental Results fromthe Ontario Heart Health Surveys (OHHS) demonstrate an increase in obesity with: Increased age (females>males) Absence of high school education Adoption of a sedentary lifestyle Nicotine consumption was a negative risk factor for obesity in the OHHS population Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
  • 19.
  • 20.
    Treatment Options forObesity Diet Therapy Pharmaceutical Agents Sibutramine Orlistat Bupropion Potential targets Surgical Therapy Gastric Banding Gastric Bypass Biliopancreatic diversion
  • 21.
    Sibutramine (Meridia ®) MOA: inhibits norepinephrine (NE) and serotonin (5-HT 2 ) neuronal uptake  enhances satiety Dose: 10 mg PO once daily x 4 wks, then may  to 15 mg daily x 100 wks Adverse Effects (>10%) Headache Insomnia Xerostomia Constipation Chaput JP, Tremblay A. Current and novel approaches to the drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
  • 22.
    Sibutramine (Meridia ®) Bray et al. (1999) Bray G, Blackburn G, Ferguson J et al. Sibutramine produces dose-related weight loss. Obes Res. 1999;7:189-98 . 46.5* 77.2* 9.0 30 101 36.5* 71.9* 8.2 20 96 34.7* 67.3* 7.0 15 98 17.2* 59.6* 5.7 10 99 12.1* 37.4 Ұ 3.7 5 107 10.5 Ұ 25.3 2.4 1 95 0 19.5 1.3 Placebo 87 >10% wt loss (%) >5% wt loss (%) Mean wt reduction (kg) Dose (mg) n
  • 23.
    STORM Trial Randomized,double-blind, placebo controlled trial Effect of weight maintenance after weight loss All patients on a 600 kcal/day deficit diet James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
  • 24.
    STORM Trial JamesW, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
  • 25.
    Sibutramine (Meridia ®) Use with caution in patients on concurrent serotonergic medications  risk of serotonin syndrome Previous black box warning Use with caution in patients with uncontrolled hypertension 12.5% patients   in BP by 15 mmHg Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  • 26.
    Bupropion MOA: inhibitsNE and DA neuronal uptake  enhances satiety Dose: 300 to 400 mg daily Non-FDA approved indication Contraindicated in patients with seizure disorders Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  • 27.
    Bupropion Anderson etal. (2002) 24 week RDBPC parallel-group study Compared placebo, 300 mg, & 400 mg daily Calorie restricted diet & lifestyle intervention program initiated Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  • 28.
    Bupropion Anderson J,Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  • 29.
    Orlistat (Alli ®, Xenical ® ) MOA: reversible inhibitor of gastric and pancreatic lipases  decreases dietary fat absorption Only FDA approved drug that directly alters metabolism Dose: 120 mg TID with meals
  • 30.
    Davidson et al.(1999) 2-year DBRPC study Diet modified to ensure adequate fat intake Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
  • 31.
    Orlistat (Alli®, Xenical®)Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
  • 32.
    Concerns with orlistat: in fat-soluble vitamin deficiency Gastrointestinal adverse effects common Fatty/oily stool (20%) Oily spotting (26.6%) Fecal incontinence (7.7%) Fecal urgency (22.1%) Flatulence with discharge (23.9%) Orlistat (Alli®, Xenical®) Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  • 33.
    Other Medications Metformin1700 mg daily  300 kcal intake reduction/30-minute eating period  hunger ratings Topiramate 65.2% of patients had weight loss of 0.5 kg to 19.5 kg in migraine study 200 mg daily  average body weight  5.9 kg Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  • 34.
    Future Pharmacologic AgentsRecombinant human leptin Neuropeptide Y antagonists GLP-1 Ghrelin antagonists Endocannabinoid receptor antagonists Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  • 35.
    Rimonabant MOA: CB1 receptor antagonist Dose: 20 mg daily Adverse Effects: suicidal ideation, anxiety, depression Not available in US NDA withdrawn
  • 36.
    RIO Trials EfficacyDecreased body weight (-6.6 kg) Decreased waist circumference (-3.9 cm) Decreased BP (-1.8 mmHg SBP) Decreased A1c (0.7%) No decrease in LDL, total cholesterol Safety RR 1.9 for any psychiatric disorder 2.5x more likely to discontinue medication due to depression Idelevich E, Kirch W, Schlinder C. Current pharmacotherapeutic concepts for the treatment of obesity in adults. Therapeutic Advances in Cardiovascular disease. 2009;3:75-90.
  • 37.
    Leptin Peptide thatacts on the hypothalamus to modulate body weight, intake and fat stores Leptin deficiency  early onset obesity Treatment options: Leptin analogues > native leptin Leptin gene promoters CNTF may also potentiate leptin-like effects Chaput J, Tremblay A. Current and novel approaches to drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
  • 38.
    Bariatric Surgery Onlyoption for treatment of morbidly obese 20-fold increase in procedures in last 10 years Types of surgery Restrictive Malabsorptive Combination Steinbrook R. Surgery for severe obesity. NEJM. 2004;350:1075-79. Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.
  • 39.
    Gastric Bypass Restrictiveand malabsorptive Causes early satiety and incomplete nutrient digestion and absorption Roux-en-Y surgery Creation of 15-30 cm gastric pouch Connection of jejunum to gastric curvature Bypasses portion of stomach, duodenum, and portion of jejunum Most common bariatric surgery Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  • 40.
    Gastric Bypass ComplicationsMortality rate: 0.5% Early complications: anastomotic leak, PE, infection Late complications: strictures, bowel obstruction, malnutrition, dumping syndrome Outcomes 62-68% excess weight loss at 2 years Initial weight loss of 70-80% excess weight Regain of weight after 2 years is common Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  • 41.
    Gastric Banding Restrictiveprocedure Implantation of inflatable silicone band around the upper stomach Band adjustments are based on individual weight loss and appetite Adjustments required 5-6 times in 1 st year Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  • 42.
    Gastric Banding ComplicationsSafest bariatric procedure available Mortality rate: 0.05-0.1% Late complications: gastric prolapse, band erosion, port infection, tubing problems Outcomes Weight loss is gradual 57% excess weight loss after 6 years Direct correlation with motivation and follow-up Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  • 43.
    Banding vs. BypassTice J, Karliner L, Walsh J et al. Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures. The American Journal of Medicine. 2008;121:885-93. 14 17 Long term complication 3.3 5.2 Short term complication 75 84 Osteoarthritis 48 37 Dyslipidemia 66 56 Hypertension 72 77 Diabetes 64 34 Weight loss Gastric Bypass (n=232) Gastric Banding (n=160) Pt characteristic (%)
  • 44.
    Biliopancreatic diversion Restrictiveand malabsorptive properties Limited gastrectomy Roux-en-Y reconstruction Patient still allowed to eat a full meal Results similar initially to gastric bypass Continued malabsorption increases 2 nd year weight loss Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Matrusso A, Roslin M, Kurian M et al. Bariatric surgery: an overview of obesity surgery. 2006;119:1357-62.
  • 45.
    Complications of BariatricSurgery Unexpected reoperation Wound dehiscence Foreign body removal laparotomy Splenic injury Hemorrhagic Intra-op hemorrhage Post-op hematoma Blood transfusion Anastomotic Leak Abdominal drainage Wound Infection Seroma dehiscence Obstruction Small bowel obstruction Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
  • 46.
    Short Bowel Syndrome(SBS) Definition: intestinal remnant <180 cm AND malabsorption Complications necessitate small bowel resection Bowel obstruction Internal hernias Mesenteric thrombosis In a review of 265 pts with SBS 15% due to bariatric surgery 82% had Roux-en-Y gastric bypass McBride C, Petersen A, Sudan D. Short bowel syndrome following bariatric surgical procedures. American Journal of Surgery. 2006;192:828-32.
  • 47.
    Outcomes in theBariatric Patient
  • 48.
    Co-morbidities following TreatmentBuchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -46.3 Biliopancreatic diversion -28.6 Gastric banding -43.5 Gastric bypass -8.6 Bupropion -7.6 Orilstat -10.2 Sibutramine Absolute weight change (kg) Treatment
  • 49.
    Co-morbidities following TreatmentBuchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. --- Biliopancreatic diversion --- Gastric banding --- Gastric bypass -1.73 Bupropion -0.8 Orilstat 0.1 Sibutramine Systolic BP (mmHg) Treatment
  • 50.
    Co-morbidities following TreatmentBuchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -5.79 Biliopancreatic diversion -3.2 Gastric banding -3.4 Gastric bypass -2.71 Bupropion 1.0 Orilstat -0.8 Sibutramine Fasting glucose (mg/dL) Treatment
  • 51.
    Co-morbidities following TreatmentBuchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. Biliopancreatic diversion Gastric banding Gastric bypass -2.95 Bupropion -20 Orilstat -0.8 Sibutramine LDL (mg/dL) Treatment
  • 52.
    Results from BariatricSurgery Co-morbidities resolve as weight ↓ Hospitalization rate increases Band adjustments Complications Complications exist Nutritional deficiencies Medication absorption issues Surgical complications Short bowel syndrome Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
  • 53.
    In the meantime . . .
  • 54.
    Dosing Controversies inObesity Weight IBW vs. ABW vs. Adjusted body weight Distribution Lipophilic vs. hydrophilic Protein bound Clearance Absorption Following bariatric surgery Erstad B. Which weight for weight-based dosage regimens in obese patients? AJHP. 2002;59:2105-10.
  • 55.
    Conclusions Obesity isbecoming more prevalent Genetic make-up may predispose pts to obesity Pharmacological agents + diet are effective for overweight patients Bariatric surgery is recommended for pts with BMI>35 Bariatric surgery is most effective treatment for obesity

Editor's Notes

  • #5 BMI is not all encompassing, waist circumference and abdominal obesity have higher prognostic factors for morbidity BMI ranges may change for certain populations . . . Asian Americans have increased risk of DM with BMI around 23. Diet and lifestyle modifications are recommended for pts with BMI of 27 + and concurrent comorbidities or BMI &gt; 30; bariatric surgery is indicated for pts with class II obesity and at least 1 comorbiditiy and class III obesity
  • #7 These numbers have doubled in the past decade and are expected to double again by 2015.
  • #10 Risk of developing diabetes with a BMI of 35 vs 22 is 40-90 fold higher, greater risk in obese females
  • #15 Replacement of leptin via subcutaneous injection in a 9 y/0 with congenital leptin deficiency led to complete reversal of obesity after 1 year of leptin treatment MC4R: melanocortin 4 receptor; autosomal dominant forms of obesity mutates the gene that encodes M4CR
  • #17 We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptee who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese. There was a strong relation between the weight class of the adoptee and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02. There was no relation between the weight class of the adoptee and the body-mass index of their adoptive parents. Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class. Furthermore, the relation between biologic parents and adoptee was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat. We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.
  • #19 Absence of high school education increased female BMI by 1.52 kg/m2 and male BMI by 0.9 kg/m2
  • #22 Approved by the FDA in 1997. A beta-phenylethylamine that exhibits monoamine reuptake inhibitor activity for NE and 5ht2 and to a lesser extent, also dopamine Differs from fenfluramine and dexfenfluramine as it does not potentiate the release of NE and 5HT2 Active metabolites cause the hypophagic properties of sibutramine Exerts it’s affects by increasing the activity of other receptors via the increased levels of NE and 5HT2, namely alpha and beta receptors and 5HT2a/2c receptors Sibutramine and cardiovascular effects: Increases HR by 4 bpm Increases SBP by 4 mmHg Increases DBP by 2-4 mmHG Can be tolerated in pts with controlled htn.
  • #24 Silbutramine Trial of Obesity Reduction and Maintenance Trial
  • #28 24 week multicenter, randomized, placebo controlled, double blind, parallel group study
  • #33 Rates of GI effects decreased over 2 years, 5.5%, 4.4%, 1.8%, 2.8%, 2.1% respectively
  • #34 Metformin most likely alters leptin levels
  • #36 CB receptors are widely distributed throughout the body, including in the brain and areas related to feeding, fat cell, GI tract. CB2 receptors are expressed in the immune system. Fasting increases levels of cannabinoids to agonist CB1 receptors, Blockade of the agonism leads to decreased stimulation for intake of high fat and sweet foods. Works opposite of marijuana. Received marketing approval from the European Medical Agency in June 2006. RR of psychiatric disorder: 1.9
  • #37 RIO= Rimbonabant in Obesity
  • #39 Increase in bariatric surgery spurred by obesity epidemic and improved outcomes of bariatric surgery. Most effective for treatment of class II and III obesity that attains long term weight loss In 2006, 177,000 people received bariatric surgery, should be &gt;200,000 for 2007 4925 procedures in 1990, 12541 in 1997, 41000 in 2000, and 63000 in 2002
  • #40 Talk about length of Roux limb and risk for dumping syndrome
  • #41 Irreversible procedure, take-down can happen if needed.
  • #42 Laparoscopic adjustable gastric banding Best for women who wish to bear children as the band can be maximally deflated to allow for adequate nutritional intake with the fluctuating caloric needs of the pregnant woman Bands are usually not removed, even after adequate weight loss has been attained Poor candidates for LAGB are those who have severe obesity (BMI &gt;50), severe abdominal adiposity, chronic dysfunction of the GI tract (GERD). Outpatient procedure!
  • #43 Early complications: band failure, slippage, difficulty swallowing
  • #44 Bariatric procedure rates have increased exponentially Banding is promoted as a safer, potentially reversible and effective alternative to bypass. Evaluation of what procedure should be standard of care.
  • #45 Also called the duodenal switch