TREATING THE ENDOTHELIUM TO RESTORE INSULIN SENSITIVITY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近的研究表明，心血管治疗对预防糖尿病的影响仍然无法解释。 我们假设这些疗法改善了血管内皮功能，从而改善了胰岛素在血管系统中的作用，这构成了胰岛素代谢作用的重要部分。 因此，我们建议测量胰岛素介导的葡萄糖处置和胰岛素介导的血管舒张治疗前后4周氯沙坦（血管紧张素受体阻滞剂）或安慰剂，在一个随机交叉设计。 受试者将包括14例糖耐量受损受试者，糖耐量受损通常伴有胰岛素抵抗和血管功能受损。 排除标准包括明确的高血压、糖尿病或高胆固醇血症，以及氯沙坦治疗的生化或其他禁忌症。 统计分析的主要终点将是胰岛素刺激的内皮功能的侵入性测量。 我们预期氯沙坦治疗后胰岛素作用的血管和代谢指标均有所改善，但安慰剂治疗后与未治疗基线相比无变化。

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.