Metabolic Surgery Mechanisms of Actions the Foregut Theory

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  • Page d’acceuil de la Présentation Titre + photo IRCAD + Logo IRCAD & EITS
  • Metabolic Surgery Mechanisms of Actions the Foregut Theory

    1. 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. 2. Rates of Remission of Diabetes Adjustable Gastric Banding Roux-en-Y Gastric Bypass Biliopancreatic Diversion >95% (Immediate) 48% (Slow) 84% (Immediate)
    3. 3. Rehfeld J, 2004 1967 – Gastric Bypass DISCOVERY OF GASTROINTESTINAL HORMONES
    4. 4. Duodenal-Jejunal Bypass (DJB)
    5. 5. January 2004
    6. 6. DJB <ul><li>Controls type 2 diabetes in non obese rats independently on: </li></ul><ul><li>weight loss </li></ul><ul><li>decreased caloric intake </li></ul><ul><li>nutrients malabsorption </li></ul>Ann Surg 2004 Ann Surg November 2006
    7. 7. Gastrointestinal Bypass Surgery Direct Antidiabetic Effect > Type 2 Diabetes: an operable disease ?
    8. 8. The Surgeon and the Diabetologists
    9. 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. 10. November 2006
    11. 11. Goto-Kakizaki Rat (GK) <ul><li>Animal model of type 2 diabetes </li></ul><ul><ul><li>The most-widely used lean model in type 2 diabetes research </li></ul></ul><ul><ul><ul><li>( Nature Genet 1996 ) </li></ul></ul></ul><ul><ul><ul><li>Non-obese </li></ul></ul></ul><ul><ul><ul><li>Normolipidemic </li></ul></ul></ul><ul><ul><ul><li>Hyperinsulinism </li></ul></ul></ul><ul><ul><ul><li>Insulin resistance </li></ul></ul></ul>
    12. 12. Gastro-jejunal Anastomosis <ul><ul><li>Early Ileal Stimulation </li></ul></ul>Annals of Surgery Nov 2006
    13. 13. (GJA) DJB Sham + PF to DJB Annals of Surgery Nov 2006
    14. 14. Oral Glucose Tolerance Annals of Surgery Nov 2006
    15. 15. Oral Glucose Tolerance Annals of Surgery Nov 2006
    16. 16. Oral Glucose Tolerance Annals of Surgery Nov 2006
    17. 17. Duodenal Exclusion Annals of Surgery Nov 2006
    18. 18. OGTT after Doudenal Exlcusion P<0.05 Annals of Surgery Nov 2006
    19. 19. Restoration of Duodenal Passage AUC OGTT X 2 Annals of Surgery Nov 2006
    20. 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
    21. 21. Implication for the Pathophysiology of T2D <ul><li>Nutrients contact with duodenal mucosa is detrimental </li></ul><ul><li>in diabetic rats </li></ul><ul><li>A dysfunctional duodenal response to nutrients passage </li></ul><ul><li>plays a role in the pathophysiology of type 2 diabetes </li></ul>
    22. 22. Hypothesis Hypoglycemia <ul><ul><ul><li>Rubino et al; Ann Surg 2002 </li></ul></ul></ul>
    23. 23. Hypothesis <ul><ul><ul><li>Rubino et al; Ann Surg 2002 </li></ul></ul></ul>
    24. 24. Hypothesis <ul><ul><ul><li>Rubino et al; Ann Surg 2002 </li></ul></ul></ul>
    25. 25. Hypothesis <ul><ul><ul><li>Rubino et al; Ann Surg 2002 </li></ul></ul></ul>
    26. 26. GIP and GLP-1 <ul><li>Stimulated by enteral nutrients </li></ul><ul><li>insulin secretion / action </li></ul><ul><li> -cell proliferation </li></ul>… Anti-Incretin <ul><li>Stimulated by enteral nutrients </li></ul><ul><li>insulin secretion / action </li></ul><ul><li> -cell proliferation </li></ul>Anti-incretin
    27. 27. Anti-Incretin Insulin Resistance Beta cell depletion Hyperglycemia Too much Dumping Syndrome Nesidioblastosis Hyperinsulinemia Hypoglycemia Not Enough TYPE 2 DIABETES
    28. 28. Conclusions <ul><li>Our findings in rats support the hypothesis that a dysfunction of the duodenum may contribute to the pathophysiology of type 2 diabetes </li></ul>

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