TREATING THE ENDOTHELIUM TO RESTORE INSULIN SENSITIVITY

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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. Recent studies suggesting an effect of cardiovascular therapies to prevent diabetes remain unexplained. We hypothesize that these therapies improve vascular endothelial function allowing improved actions of insulin in the vasculature, which comprise a significant portion of insulin's metabolic action. We therefore propose to measure insulin-mediated glucose disposal and insulin-mediated vasodilation before and after 4 weeks therapy with Losartan (an angiotensin receptor blocker) or placebo, in a randomized crossover design. Subjects will include 14 subjects with impaired glucose tolerance, which is generally accompanied by both insulin resistance and impaired vascular function. Exclusion criteria will include frank hypertension, diabetes, or hypercholesterolemia, and biochemical or other contraindications to losartan therapy. The primary endpoint for statistical analysis will be the invasive measure of insulin stimulated endothelial function. We anticipate an improvement in both vascular and metabolic measures of insulin action following Losartan therapy but no change from untreated baseline following placebo.