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Anti Diabetes Operations: The Foundation for New Procedures
 

Anti Diabetes Operations: The Foundation for New Procedures

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  • This is “KEY”reference that’s why the key symbol is on the slide
  • This is “KEY”reference that’s why the key symbol is on the slide
  • JIB ultimately abandonned secondary to complications
  • as the DJB model leaves the stomach undisturbed
  • This leads to the next important question….Should patients with Ype 2 DM be considered for surgical treatment regardless of their BMI? Mention that interestingly, sporadic observations of diabetes remission have also been reported before the advent of bariatric surgery as a serendipitous outcome of gastric resection for peptic ulcer in non obese patients; In 1955 Freidman reported 3 patients with uncontrolled DM for years who had sudden reduction in insulin requriement 3-4 days after subtotal gastrectomy, long before substantial weight loss.
  • What about diabetic patients with normal BMI? Can surgery be considered for non-obese diabetic patients
  • MUST CLICK TWICE TO GET TO NEXT AND FINAL SLIDE !!!!!!!

Anti Diabetes Operations: The Foundation for New Procedures Anti Diabetes Operations: The Foundation for New Procedures Presentation Transcript

  • Anti-Diabetes Operations : The Foundation for New Procedures George S.Ferzli, M.D., Giancarlo Cires, M.D., Benjamin Chandler, Rosemarie E.Hardin, M.D. Metabolic Surgery Symposium New Mexico, 2007
  • Background
    • Impaired insulin secretion and insulin resistance both contribute to Type II DM
    • The causes of these alterations are not fully elucidated
    • Current therapies include: diet, exercise, oral hypoglycemics, insulin, and behavior modification
    Problem??? None of these options offers a cure!!! Solution: BARIATRIC SURGERY??
  • Francesco Rubino . Bariatric Surgery:Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care. 9:497-507
    • Bariatric surgery may provide new possibilities for “ cure ” of Type 2 DM
    • Clinical evidence supports operations for morbid obesity induces significant weight loss but leads to improvement or resolution of comorbid disease states, particularly Type 2 DM
    • RYGB and BPD are the most effective in controlling DM
    • Both result in sustained normal concentrations of plasma glucose, insulin & Hgb A1C in 80-100% of morbidly obese patients with DM
    • Insulin sensitivity is increased 4-5 x after RYGB-induced weight loss
    • RYGB and BPD prevents progression from impaired tolerance to DM
  • Francesco Rubino . Bariatric Surgery:Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care. 9:497-507
    • The resoultion of DM after RYG and BPD occurs too fast to be accounted for by weight loss alone
    • RYGB and BPD must have direct impact on glucose homeostasis
     
  • Buchwald H, Avidor Y, Braunwald E. et al. Bariatric Surgery: A Systemic Review & Meta-analysis. JAMA 2004; 292:1724-1737
    • Involved 136 studies
    • N=22,094 patients
    • Focused on the effect of bariatric surgery on obesity co-morbidities
    • T2 DM completely resolved in 76.8 % of patients
    • Improved in 86 %
    • Lowered the rate of progression from impaired glucose tolerance to DM by 30 fold
  • Buchwald H, Avidor Y, Braunwald E. et al. Bariatric Surgery: A Systemic Review & Meta-analysis. JAMA 2004; 292:1724-1737
    • With respect to diabetes resolution; ability to discontinue all diabetes-related medications,maintain normal fasting glycemia,normalization of glycosylated hemoglobin a gradation of effect was demonstrated
      • 98.9% for BPD or duodenal switch
      • 83.7% for RYGB
      • 71.6% for VBG
      • 47.9% for LAGB
  • Anti-diabetic Effect of Bariatric Surgery
    • Intestinal Malabsorption
      • Weight loss reduces insulin resistance
      • Glucose malabsoprtion reduces stress on islet cells
      • Fat malabsorption reduces circulating free fatty acids and improves insulin sensitivity
    • Hormonal Changes
      • Re-routing of food alters the dynamic of gut-hormone secretion
        • Decrease in plasma levels of leptin & insulin
        • Increased levels of adiponectin & peptide YY3-36
        • Increased levels of glucagon-like peptide 1 (GLP-1)
    • Rearrangement of GI anatomy
      • “ Hindgut hypothesis”
      • “ Foregut hypothesis”
  • Foregut vs. Hindgut
    • Foregut hypothesis suggests exclusion of duodenum and proximal jejunum from the transit of nutrients may interrupt signals that lead to insulin resistance and Type 2 DM
    • Hindgut hypothesis suggests enhanced delivery of nutrients to distal ileum alters secretion of hormones & improves glucose metabolism
    • *** GLP-1 may be a major mediator of this effect
    Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Proposed Mechanism?
  • Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
    • Rubino et al tested hypothesis on Goto-Kakizaki rats
    • Rats underwent either DJ bypass or gastrojejunostomy
    • DJ bypass = Forgut hypothesis
    • Gastrojejunostomy = Hindgut Hypothesis
  • Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
    • RESULTS
    • DJ bypass rats had better oral glucose tolerance
    • Gastrojejunostomy did not affect glucose homeostasis
    • Rats with GJ who then had duodenal exclusion had improved glucose homeostasis
    • Supports proximal intestinal bypass for treatment of DM
  • Pacheco D . The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakazi rats. Am J Surgery; 194 (2007):221-224
    • 12 rats underwent either DJ bypass or no intervention
    • Basal glucose levels at time 0 in basal time, at 1 week, and at 1 month were lower in group 1 than group 2.
    • Post oral glucose overload levels of glucagon, insulin, GLP-1, and GIP remained unchaged during the treatment in both groups.
    • In group 1, leptin levels had a significant decrease at 1 week and 1 month after surgery
  • Diabetes Operations
    • Restrictive
    • Malabsorptive
    • Mixed procedures
  • Restrictive Procedures
    • Create a small gastric pouch
    • Includes laparoscopic adjustable gastric band and vertical banded gastroplasty
    • There is no bypass of intestinal contents
    • Not as effective in controlling DM
  • Roux-en-Y Gastric Bypass
    • Considered gold standard for obesity surgery
    • May be done open or laparoscopically
    • Stapler is used to create small gastric pouch
    • After RYGB, ingested food bypasses approximately 95% of the stomach, the entire duodenum and a portion of the jejeunum; usually results in 60-70% excess weight loss and most of this effect is maintained for at least 15 years
    Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Malabsorptive Procedures
    • Reduce the area of intestinal mucosa available for nutrient absorption
    • First attempt to obtain weight loss through this strategy was through the jejunoileal bypass
    • JIB diverted nutrients from small intestine by anastomosing the proximal jejunum to terminal ileum
    • Drawback: excessive long term nutritional complications and hepatic cirrhosis due to bacterial; overgrowth
    Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Jejunoileal Bypass
    • Proximal jejunum is anastamosed to terminal ileum
    • Diverts enteral nutrients from most of small intestine
    • Results:good weight loss
    • Long term complications include bacterial overgrowth and cirrhosis
    Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Biliopancreatic Diversion
    • First described by Nicola Scopinaro of Genoa, Italy in 1979
    • Partial gastrectomy,leaves behind a 200-500 cc size upper stomach
    • Re-anastomosed to distal 250cm of small intestine
    • Bypassed biliopancreatic limb attached 50cm proximal to iliocecal valve
    • The last segment of ileum where food and bile mix is referred to as a “common channel” and is responsible for most fat absorption
    Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Duodenal Switch Duodenal switch variant involves sleeve gastrectomy and preservation of pylorus and short segment of duodenum
  • Anti-diabetic Effect of Bariatric Surgery
    • Prospective Swedish Obese Subjects Study
    • Involved obese patients who underwent gastric surgery & matched, conventially treated obese controls
    • Follow up 2 years (n=4047) & 10 years (n=1703)
    • Surgery lead to more dramatic improvement in diabetes control than conventional therapy
  • Direct Effect or Secondary Gain?
    • Evidence suggests control of DM after GI bypass surgery is not secondary to weight loss
    • Spontaneous model of non obese Type 2 DM using Goto Kakizaki rats
    • Demonstrated that duodenal jejunal bypass ( a stomach sparing experimental model of RYGB) significantly improved glucose tolerance in comparison to sham operations.
    • This study allowed the effects of intestinal bypass to be isolated from those related to gastric restriction *
    DM Type 2 is a potentially operable disease Rubino F. Bariatric Surgery: Effects on Glucose Homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
  • Bariatric Surgery for Control of DM in non-obese patients???
    • Current indications for bariatric surgery include BMI > 40 kg/m 2 or BMI between 35-40 kg/m 2 with obesity-related co-morbidities
    • Bariatric surgery has been occasionally performed in nonmorbidly obese individuals; 1977: Mingrone reported a case of a young, non obese woman with DM who underwent BPD for chylomicronemia
      • Result???
      • Plasma insulin and blood glucose levels normalized within 3 months
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
    • 39 patients underwent laparoscopic ileal interposition into proximal jejunum via sleeve or diverted sleeve gastrectomy
    • Patients had BMI < 35
    • All had type II DM for at least 3 years
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
    • Mean operative time was 185 minutes
    • Mean post-op follow up was 7 months
    • 87% of patients discontinued preop oral hypoglycemics, insulin, or both
    • Hemoglobin A1c decreased from 8.8% to 6.3%
    • All but one patient experienced normalization of cholesterol
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
  • DePaula AL . et al. Laparoscopic treatment of type 2 DM for patients with BMI less than 35. Surg Endosc. In press
  • FUTURE?????