Type 2 Diabetes: A Surgical Disease??? <ul><li>The prevalance of obesity and diabetes mellitus is rising & strongly linked...
Historic Perspective <ul><li>“ Diabetes remission has been reported before the advent of bariatric surgery as a  serendipi...
Historic Perspective <ul><li>Bittner  et al. also reported amelioration of diabetes with lowered plasma glucose and insuli...
Should patients with type 2 DM be considered for surgical treatment regardless of their BMI ? <ul><li>Current indications ...
DJ Bypass & Glucose Metabolism <ul><li>Bariatric Surgery clearly has an antidiabetic effect; thought to be secondary to su...
 
Animal Model of DJ bypass and Glycemic Control <ul><li>Animal Model of nonobese type 2 diabetes; Goto-Kakizaki rats </li><...
 
Results of DJ Bypass on Glycemic Control <ul><li>Group 1 and Group 2 rats remained the same weight during the experiment <...
Leptin??? <ul><li>Adipocyte-derived hormone </li></ul><ul><li>In mice, leptin acts as a hormonal signal on the afferent li...
Reversal of Insulin Resistance by Leptin
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Type 2 Diabetes & Surgical Disease

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  • This raises an interesting question?????
  • To make a joke: it’s funny that in 1955 this was published in Obstetrics journal….OB/GYN’s were 50 years ahead of general surgeons!!!!!
  • To make a joke: it’s funny that in 1955 this was published in Obstetrics journal….OB/GYN’s were 50 years ahead of general surgeons!!!!!
  • This would revolutionize bariatric surgery
  • Hypothesis regarding the possible contribution of the proximal intestine to the alterations of glucose metabolism in type 2 diabetes
  • Type 2 Diabetes & Surgical Disease

    1. 1. Type 2 Diabetes: A Surgical Disease??? <ul><li>The prevalance of obesity and diabetes mellitus is rising & strongly linked to DM with accompanying insulin resistance </li></ul><ul><li>Impaired insulin secretion and insulin resistance are both causative factors in the development of Type 2 DM </li></ul><ul><li>Amelioration of Type 2 diabetes is a proven outcome of surgical treatment of obesity </li></ul><ul><li>Biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGBP) are more effective for amelioration of DM than other procedures </li></ul><ul><ul><li>May lead to normalization of glycosylated hemoglobin, plasma glucose and insulin in as much as 90-100% of morbidly obese patients with DM 1 </li></ul></ul><ul><ul><li>Insulin sensitivity is increased approximately 4-5 fold after RYGB induced weight loss 2 </li></ul></ul><ul><ul><li>Prevents progression from impaired glucose tolerance to diabetes, by as much as 30 fold 2 </li></ul></ul>1.Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007):221-224 2. Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507
    2. 2. Historic Perspective <ul><li>“ Diabetes remission has been reported before the advent of bariatric surgery as a serendipitous outcome of gastric resections for peptic ulcer in non obese patients.” </li></ul><ul><li>In 1955, Friedman reported 3 patients with DM who had poor glycemic control , despite therapy with high daily doses of insulin </li></ul><ul><ul><li>3-4 days after subtotal gastrectomy all 3 pateints showed an improvement in their DM with sudden reduction in insulin requirements </li></ul></ul><ul><ul><li>This observation occurred sooner than associated weight loss </li></ul></ul><ul><ul><li>More importantly, these patients later regained their weight without an associated loss of glucose control or glycosuria </li></ul></ul>Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 9:497-507 Friedman NM et al. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg Gynecol Obstetr 1955; 100:201-204 .
    3. 3. Historic Perspective <ul><li>Bittner et al. also reported amelioration of diabetes with lowered plasma glucose and insulin after subtotal gastrectomy and gastrointestinal reconstructions that excluded duodenal passage (B2 and RYGB) </li></ul><ul><li>Conclusion: Plasma glucose and insulin fall rapidly and antidiabetic medications can be reduced or stopped shortly after gastrointestinal bypass interventions </li></ul>Rubino F. Bariatric Surgery:effects on glucose homeostasis. Curr OpiClin Nutr Metab Care 9:497-507 Bittner R. Homeostasis of glucose and gastric resection: the influence of food passage through the duodenum. Z Gastroenterology 1981; 19:698-707.
    4. 4. Should patients with type 2 DM be considered for surgical treatment regardless of their BMI ? <ul><li>Current indications for bariatric surgery include BMI = or > than 40 kg/m 2 or between 35 and 40 kg/m 2 with obesity-related comorbidities </li></ul><ul><li>All bariatric operations are performed based on these specific criteria; therefore, the antidiabetic effects of bypass surgery is well documented in this population of severely or morbidly obese patients </li></ul><ul><li>These procedures occaionally performed in non-obese individuals </li></ul><ul><ul><li>Mingrone et al. reported a case of BPD for a non obese female with chylomicronemia whose plasma insulin and blood glucose levels were normalized within 3 months </li></ul></ul><ul><ul><li>Noya et al. reported remission of type 2 DM in 9/10 moderately obese patients with mean BMI 33, who underwent BPD </li></ul></ul>
    5. 5. DJ Bypass & Glucose Metabolism <ul><li>Bariatric Surgery clearly has an antidiabetic effect; thought to be secondary to surgically induced weight loss and decreased caloric intake </li></ul><ul><li>But, how do we explain the finding that glycemic control occurs within days, before significant weight loss has been achieved??? </li></ul><ul><ul><li>Direct effect of the surgical bypass of proximal intestines </li></ul></ul><ul><ul><li>Hormonal Regulation of Glucose Metabolism </li></ul></ul><ul><ul><ul><li>Insulin, glucagons-like peptide(GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon and leptin </li></ul></ul></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007):221-224
    6. 7. Animal Model of DJ bypass and Glycemic Control <ul><li>Animal Model of nonobese type 2 diabetes; Goto-Kakizaki rats </li></ul><ul><li>Twelve (12-14 wk old) rats randomly underwent </li></ul><ul><li>gastrojejeunal bypass or no intervention </li></ul><ul><li>* All fed with same type of diet </li></ul><ul><li>* All fed with same amount of diet </li></ul><ul><li>* Pre-op, post op 1 wk & 1 month </li></ul><ul><li>weight assessment & fasting glycemia </li></ul><ul><li>* Oral Glucose Tolerance Test performed at each </li></ul><ul><li>time point </li></ul><ul><li>* Hormone levels were measured after 20 minutes of oral </li></ul><ul><li>overload </li></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007):221-224
    7. 9. Results of DJ Bypass on Glycemic Control <ul><li>Group 1 and Group 2 rats remained the same weight during the experiment </li></ul><ul><li>OGTT improved in DJ bypass group </li></ul><ul><li>Glucose levels were better at 1 week & 1 month after DJ bypass in all times of OGTT (basal, 10 min, 120 min) </li></ul><ul><li>Postoroal glucose load levels of glucagon, insulin, GLP-1 and GIP remained unchanged in both groups </li></ul><ul><li>In DJ bypass group + significant decrease in leptin levels noted </li></ul>
    8. 10. Leptin??? <ul><li>Adipocyte-derived hormone </li></ul><ul><li>In mice, leptin acts as a hormonal signal on the afferent limb of a negative feeback loop between the adipose tissue and hypothammic centers </li></ul><ul><li>Physiological increase in plasma leptin has been shown to significantly inhibit glucose-stimulated insulin secretion in vivo and to determine insulin resistance </li></ul>Pacheco D, et al. The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats. Am J Surgery; 194 (2007):221-224
    9. 11. Reversal of Insulin Resistance by Leptin

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