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Metabolic Surgery Mechanisms of Actions the Foregut Theory
 

Metabolic Surgery Mechanisms of Actions the Foregut Theory

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Metabolic Surgery Mechanisms of Actions the Foregut Theory Metabolic Surgery Mechanisms of Actions the Foregut Theory Presentation Transcript

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