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Diabetes Surgery Update

Diabetes Surgery Update. Walter J. Pories , MD, FACS Professor of Surgery, Biochemistry, Sport and Exercise Science Brody School of Medicine, East Carolina University. 12th Annual Minimally Invasive Surgery Symposium ( MISS 2012 ), February 20-25, 2012

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Diabetes Surgery Update

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  1. Diabetes Surgery Update Walter J. Pories, MD, FACS Professor of Surgery, Biochemistry, Sport and Exercise Science Brody School of Medicine, East Carolina University 12th Annual Minimally Invasive Surgery Symposium (MISS 2012), February 20-25, 2012 Grand America Hotel in Salt Lake City, Utah

  2. Disclosures Research Grant Support NIH/NIDDK Johnson & Johnson Glaxo Smith Kline HRSA x 3 Golden LEAF Foundation Brody Foundation Would you like to add your name?

  3. The Drunk and the Dollar The Drunk and the Dollar

  4. With diabetes, it’s always about sugar In 1552 BC, ancient Hindu writings first described black flies and ants congregating around the sweet urine of unwell individuals.

  5. In 400 BC, the Indian physician Sushruta described the urine’s sweet taste, and for hundreds of years this was the foundation of diagnosis

  6. And even today, we depend on measurement of glucose to make a diagnosis of diabetes • Fasting Blood Sugar • Hb1Ac • Postprandial Blood Sugar • Glucose Tolerance Test • Glucose Clamp

  7. Insulin can resolve hyperglycemia!December 30, 1921

  8. Sir Harold Himsworth (January 1936): • There are two forms of diabetes: • T1DM • T2DM • It took 15 years………… • Insulin adopted as the only effective treatment for both diseases

  9. And still today, according to the American Diabetes Association (ADA Website: 10/2011) • “In type 1 diabetes, the body does not produce insulin.” • “In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin.” • Accordingly, the objective in the current approaches to both forms of diabetes is lower glucose levels by • increasing insulin or • reducing insulin resistance

  10. The current Treatment of T2DM Insulin Production Insulin Sensitivity Glucose # Insulin # 2 Sensitizers # 3 Secretagogues * 3.1 Sulfonylureas # 4 Alpha-glucosidase inhibitors # 5 Peptide analogs mimetics * 5.2 Amylin analogues Decrease intake Increase exercise

  11. But T2DM patients are already hyperinsulinemic Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  12. Explaining the Hyperinsulinemia • The current view: Peripheral insulin resistance requires more insulin secretion? • OR could it be due to: too much insulin secretion by islets?

  13. Hyperglycemia due to Insulin Resistance Energy Storage: Glycogen and Lipid deposition Excess Insulin Mitogen: Cancers

  14. Hyperglycemia due to XS insulin secretion

  15. Hyperglycemia due to XS insulin secretion

  16. Hyperglycemia due to XS insulin secretion Energy Storage: Glycogen and Lipid deposition Excess Insulin Mitogen: Cancers

  17. With DJB, insulin levels are restored, not due to weight loss (Lakdawalla, 6 months in lean patients)

  18. Hyperinsulinemia is corrected rapidly after RYGB

  19. Yes, beta cells finally decrease their output but exhaustion of the beta cells is a late event Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  20. Yes, maximum insulin secretion falls with progression of T2DM Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  21. BUT…. Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  22. BUT it’s still higher than insulin secretion in a normal person Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  23. Is the problem the rise in basal secretion? Insulin secretion at night, without a food stimulus? Pories, et al. Surgical treatment of obesity and its effect on diabetes. 10 year follow-up. Am. J. Clin. Nutr. 55: 582S-585S, 1992

  24. Insulin levels after mid-level caloric meal challenge

  25. Insulin levels after mid-level caloric meal challenge Basal insulin level is twice normal; can’t respond more Reed M. submitted 2011

  26. Pre-surgery Within a week, the normal insulin levels and response are corrected………… Surgery Week

  27. Pre-surgery And stay corrected……. 3 Months Post Surgery Surgery Week

  28. What can we measure to address this question? • Insulin Sensitivity: Minimal Model • Insulin secretion: Minimal Model (AIRg), Meal test (glucose sensitivity) • Glucose disposal (AUG for glucose after a meal) • Glucose production (fasting glucose)

  29. Insulin sensitivity improves at 3 months but there is still profound insulin resistance

  30. Insulin secretion does improve but is not normal until three months

  31. Glucose sensitivity of insulin secretion does not return to normal

  32. Glucose disposal remains abnormal

  33. Glucose production improves but only to IGT levels

  34. Yet Hyperinsulinemiais completely corrected at one week

  35. Yet Hyperinsulinemiais completely corrected at one week • Hperinsulinemia is corrected simultaneously with the remission of T2DM • Insulin resistance improves but is not fully corrected by three months. • Hyperinsulinemia is the primary event.

  36. The RYGB even uncouples insulin and glucose Before Surgery

  37. The RYGB even uncouples insulin and insulin sensitivity and even insulin and FFA Before Surgery After Surgery

  38. Another clue:The remission of T2DM is “dose-related” to the reduction of contact between food and the gut

  39. HOW DO THESE DIFFERENT OPERATIONS PRODUCE THE SAME RESULTS? All articles in English, 1990 – 2006, 621 studies, 888 treatment arms, 135,246 patients XS WT Loss 46.2% 57.9% ? 55% 63.6% Stop T2DM 56.7% 80.3% ? 80% 95.1% Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge, I. Meta-analysis of Bariatric Surgery and Diabetes, Am J Med (2009)122: 248 - 256

  40. If the remission of T2DM is “dose-related” to the reduction of contact between food and the gut Does food stimulate the secretion of a factor that causes diabetes? The lesion lies between the gut and the islets not out in the periphery

  41. Hypertension Diabetes Hyperlipidemias Sleep Apnea Cancer Renal failure Metabolic Syndrome NASH Central Obesity Polycystic Ovary Disease Dyslipidemias Atherosclerosis Degen. Arthritis

  42. Hypertension Diabetes Hyperlipidemias Sleep Apnea Cancer Renal failure Hyper-insulinemia? NASH Central Obesity Polycystic Ovary Disease Dyslipidemias Atherosclerosis Degen. Arthritis

  43. Oral

  44. A Modest Proposal • The current therapy of T2DM aims to increase insulin production or decrease insulin sensitivity. • Observations from bariatric surgery suggest approach needs re-evaluation. • The hyperinsulinemia of T2DM is due to excess secretion of insulin in response to diabetogenic signals from the gut. • Insulin resistance is a secondary protective response • It’s not just about T2DM; it’s about the metabolic syndrome

  45. We don’t treat hyperthyroidism with thyroxineShould we be treating T2DM with insulin?

  46. With a Final Question….. • We don’t treat hyperthyroidism with thyroxine • Should we be treating T2DM with insulin?

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