GLUCOSE METABOLISM IN THE IMMEDIATE AND SHORT-TERM FOLLOW-UP AFTER BARIATRIC

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a study for evaluation immediate and short-term follow-up outcome of glucose metabolism; insulin resistance, insulin secretion and gut hormones profile in type 2 diabetic subjects undergoing bariatric surgery. Specifically, this study is designed to investigate mechanisms and rates of improvement and possibly reversal of type 2 diabetes mellitus following bariatric surgery. We hypothesize that long before dramatic weight loss is achieved with bariatric surgery, there is a marked improvement in glucose metabolism in patients with type 2 diabetes due to several mechanisms. We anticipate a decrease of ¿¿lipotoxicity¿¿ (i.e. decrease in adipocyte hormones and free fatty acids), leading to improvement of insulin resistance and perhaps more importantly, a marked improvement in the capacity for insulin secretion due not only to alleviation of insulin resistance, but also by specific effects of Roux-en-Y procedures on the entero-insular axis of gut hormones and subsequent effects on ¿¿-cell function. Specific aim of the study will concern the rate of improvement of pancreatic B cell function (measurement of insulin secretion in response to IV and oral glucose), gut hormone secretion, and overall glucose metabolism immediately following bariatric surgery.Two weeks prior to surgery, type 2 diabetic subjects will undergo a standard 75 gram oral glucose tolerance test and hyperglycemic clamp to assess insulin secretion and sensitivity (whole body glucose disposal) performed in the General Clinical Research Center (as outpatient visits). Following surgery, at 2 days, 2 weeks and 2 months subjects will undergo hyperglycemic clamp and oral glucose tolerance test (2 weeks and 2 months only). During these tests, measurements will include plasma levels of glucose, insulin , C-peptide, free fatty acid levels and adipocyte hormone profile (adiponectin, leptin, TNF-¿¿, and IL-6). A gut hormone profile (ghrelin, glucagons-like-peptide 1 GLP-1, glucagon, PYY) will be performed at fasting and specific postprandial times. Results will be compared between two groups: patients undergoing laposcopic Roux-n-Y gastric bypass and gastric banding