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. The Insulin Resistance Syndrome (IR) provides the 'common soil' for the development of type 2 diabetes and cardiovascular disease and is responsible for extensive morbidity and mortality in our society. Bariatric surgery (BS) offers an efficacious treatment for sustained weight loss for morbidly obese patients. The metabolic improvements associated with the surgical procedure include enhancement of insulin release, insulin resistance, and glucose utilization. The mechanisms underlying the improvement in insulin sensitivity in these patients are not understood, and may be related to the marked reduced caloric and macronutrient intake, as well as to the fat malabsportion induced by the procedure. Additionally, the BS model provides the opportunity to study the effect of bypassing most of the stomach and duodenum on the entero-insular axis, and its subsequent effects on different metabolic pathways as well as satiety regulatory mechanisms. Therefore, we want to expand the subjects' inclusion criteria in our current grant, to obese subjects who attain weight loss through BS. In accordance to our current hypotheses, the overall goal of this study will be to determine the effect of BS on insulin sensitivity, the entero-insular axis, and intramyocellular fat. Subjects receiving BS will be recruited for the study. The study will have 3-phases- Phase I: 1-4 wks before surgery; Phase II: 3-6 months after surgery; and Phase III: 12-18 months after surgery.
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