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

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

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