1. Metabolic Surgery Mechanisms of Actions The Foregut Theory Francesco Rubino, MD Department of Surgery, Catholic University, Rome, Italy United States Surgical Metabolic Surgery Panel June 14, 2007 San Diego, CA

2. Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immediate) 48% (Slow) 84% (Immediate)

3. Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES

4. Duodenal-Jejunal Bypass (DJB)

5. January 2004

7. Gastrointestinal Bypass Surgery Direct Antidiabetic Effect > Type 2 Diabetes: an operable disease ?

8. The Surgeon and the Diabetologists

9. Mechanisms of Surgical Treatment of T2D The exclusion of the duodenal nutrient passage may offset an abnormality of gastrointestinal physiology responsible for insulin resistance and type 2 diabetes « Foregut hypothesis »

10. November 2006

13. (GJA) DJB Sham + PF to DJB Annals of Surgery Nov 2006

14. Oral Glucose Tolerance Annals of Surgery Nov 2006

15. Oral Glucose Tolerance Annals of Surgery Nov 2006

16. Oral Glucose Tolerance Annals of Surgery Nov 2006

17. Duodenal Exclusion Annals of Surgery Nov 2006

18. OGTT after Doudenal Exlcusion P<0.05 Annals of Surgery Nov 2006

19. Restoration of Duodenal Passage AUC OGTT X 2 Annals of Surgery Nov 2006

20. Conclusion Exclusion of the proximal small bowel from the flow of nutrients is the primary mediator of diabetes resolution after DJB Annals of Surgery Nov 2006

27. Anti-Incretin Insulin Resistance Beta cell depletion Hyperglycemia Too much Dumping Syndrome Nesidioblastosis Hyperinsulinemia Hypoglycemia Not Enough TYPE 2 DIABETES