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Evolving Treatment Strategies: The Complexity of Energy Homeostasis

Evolving Treatment Strategies: The Complexity of Energy Homeostasis. Artificial sweetners lead to weight gain?. Energy In (Caloric Intake). Energy Balance and Body Weight: What is Metabolism?. Body Weight. Energy Out (Metabolism). Energy Homeostasis: The Quick Fix?. New Set Point.

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Evolving Treatment Strategies: The Complexity of Energy Homeostasis

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  1. Evolving Treatment Strategies:The Complexity of Energy Homeostasis Artificial sweetners lead to weight gain?

  2. Energy In (Caloric Intake) Energy Balance and Body Weight:What is Metabolism? Body Weight Energy Out (Metabolism)

  3. Energy Homeostasis:The Quick Fix?

  4. New Set Point The Diet StrategyFailure Rate of Diet Alone 90-98% Baseline Weight ↓ 5-10% Counter-Regulation

  5. Weight ManagementCounter-Regulation and the Failure of the “Diet” – HCG Diet

  6. Weight LossCounter-Regulation and the Failure of the “Diet” – Ideal Protein 308 295 Ideal Protein Diet ↓ 28% Fatigue, Depression, Fibromyalgia, Sleep Disorder, “Must be something hormonal” 211

  7. Energy In (Caloric Intake) Energy Balance and Body Weight:What is Metabolism? Body Weight Energy Out (Metabolism)

  8. Low MetabolismHow Do I Fix It? – “Get Your Ducks in a Row” • Sleep Problems – Sleep Apnea • Vitamin D Deficiency • Thyroid • Vitamin B12 • Low Testosterone (male) • Medications (centrally acting)

  9. Energy Homeostasis:The Miracle Pill?

  10. Rimonobant Sibutramine (Meridia) Phentermine Topiramate (Topomax) Tesofensine (NS2330) Belviq Lorcaserin (5HT2C) Hormones Insulin Leptin Ghrelin PYY CCK Adiponectin Psychological Pleasure Reward Visual Olfactory Taste Energy Homeostasis:The Search for the Magic Pill? Mechanical Gastric Distension Weight Loss Pills Belviq N=8,000 52-104 weeks Weight Loss: 3-3.7% over placebo 47% loss >5% Dosing: 10mg BID Qsymia N=3,700 52-104 weeks Weight Loss: 6.7-8.9% over placebo 70% loss >5% Dosing: 3.75/23mg, 7.5/46mg, 11.25/69mg, 15/92mg Substrates Glucose Aminoacids Free Fatty Acids Lipids Empatic (bupropion + zonisamide) Contrave (bupropion + naltrexone) Neural Vagal Afferents The Miracle Pill Making Progress?? Dopamine, Cannabanoids Norepinephrine, NPY Serotonin, POMC, GABA etc… 4-8% Total body weight loss Not sustainable 20-30% Non-response rate Qsymia (phentermine + topiramate) Hypothalmus Energy Balance Center

  11. Impaired Insulin Secretion Islet a-cell Increased Glucagon Secretion Islet b-cell Neurotransmitter Dysfunction The Ominous Octet – Treatment Strategies DecreasedIncretin Effect Increased Lipolysis Surgery? Increased Glucose Reabsorption Increased HGP Decreased Glucose Uptake

  12. ADA Clinical Practice Recommendations 2011:Changing Treatment Paradigms

  13. Energy Homeostasis:A Role for Surgery? X Lap Band Restriction of caloric intake Gastric Bypass (Roux-En-Y) Restriction of caloric intake Malabsorption of nutrients

  14. Gastric Bypass: Five Operations CONFIDENTIAL

  15. Gastric Bypass: Five Operations • Isolation of gastric cardia CONFIDENTIAL

  16. Gastric Bypass: Five Operations • Exclusion of distal stomach CONFIDENTIAL

  17. Gastric Bypass: Five Operations • Exclusion of duodenum and proximal jejunum CONFIDENTIAL

  18. Gastric Bypass: Five Operations • Exposure of distal jejunum to undigested nutrients CONFIDENTIAL

  19. Gastric Bypass: Five Operations • Partial vagotomy CONFIDENTIAL

  20. Energy Homeostasis:A Role for Surgery? Sleeve Gastrectomy Stomach becomes a “sleeve” Alters signaling mechanisms Independent glycemic effect

  21. Metabolic Surgery: The STAMPEDE Trial Type 2 DM, A1c > 7.0%, BMI 27 - 43 N = 150, single center, one surgeon Intensive Medical Therapy No Surgery Sleeve Gastrectomy Gastric Bypass Primary Outcome: Proportion with A1c < 6.0% at 12 months

  22. Metabolic Surgery: The STAMPEDE Trial

  23. Metabolic Surgery: The STAMPEDE Trial

  24. THE END

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