Mechanisms of Diabetes Control After Weight Loss Surgery

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6-Abstract- The mechanisms of type 2 diabetes (T2DM) remission after gastric bypass surgery (GBP) are unclear. The levels of the gut hormones incretins and their effect on insulin secretion, which is impaired in T2DM, markedly increase after GBP. The anatomical changes of GBP, rather than weight loss, seem to be responsible for the changes of incretins. The objective of this proposal is to investigate the different mechanisms by which GBP and gastric banding (GB) affect glucose control. We wish to understand the role of weight loss versus changes in gut peptides in the short and long term in morbidly patients with T2DM randomized to GBP or GB. AIM 1 will compare the short term effect of GBP and GB on incretin levels and effect after an equivalent 10 kg weight loss, testing the hypothesis that incretin levels and effect will increase more after GBP than after GB. AIM 2 will study the long-term changes in the incretin levels and effect after oral glucose and during a 24-h multiple meal diet, before and 2 years after GBP and GB, testing the hypothesis that mean incretin levels is greater after GBP than after GB. AIM 3 will study the changes of insulin secretion in response to IV glucose (AIRg) and insulin sensitivity (Si), measured by the minimal model, 2 years after GBP and GB, testing the hypothesis that for an equivalent increase of Si, AIRg will increase more after GBP than after GB.