INSULIN SENSITIVITY, HEMDYNAMICS AND ENDOTHELIAL FUNCTION IN WOMAN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 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。 先兆子痫是妊娠期特有的高血压疾病，是孕产妇和新生儿发病率和死亡率的主要原因。 内皮功能障碍是先兆子痫的病理生理学的中心特征，并且已经表明导致内皮功能障碍的机制包括高胰岛素血症、血脂异常和高心输出量。 产后胰岛素抵抗和高心输出量持续存在，表明这些妇女有潜在的疾病。 目前尚不清楚是否存在与代谢综合征相关的其他特征，以及这些特征是否与内皮功能障碍相关并导致内皮功能障碍。 因此，本提案的具体目的是：1）评价有先兆子痫病史的产后妇女的胰岛素抵抗和代谢综合征的特征，这些特征被认为有助于内皮功能障碍，和2）通过评价用胰岛素增敏剂改善胰岛素抵抗后这些异常的改善，探索胰岛素抵抗和这些确定的特征之间的关系。 一项旨在检查特定目标1的横断面研究将阐述以下假设：与无先兆子痫病史的女性相比，有先兆子痫病史的产后女性具有胰岛素抵抗，并具有代谢综合征的特征（中心性肥胖、血脂异常、心输出量升高和内皮依赖性血管舒张功能降低）。 一项双盲、安慰剂对照的随机研究将在6个月交叉研究中使用胰岛素增敏剂罗格列酮，在基线、6个月和12个月进行测量，以解决第二个假设。

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. Pre-eclampsia, a hypertensive disorder unique to pregnancy, is leading cause of maternal and neonatal morbidity and mortality. Endothelial dysfunction is a central feature in the pathophysiology of pre-eclampsia and mechanisms that have been suggested to contribute to the endothelial dysfunction include hyperinsulinenmia, dyslipidemia, and high cardiac output. Insulin resistance and high cardiac output persist postpartum, suggesting that these women have an underlying disorder. It is unknown whether there is persistence of other features commonly associated with the metabolic syndrome and whether these features are linked and contribute to endothelial dysfunction. Thus, the specific aims of this proposal are: 1) Evaluate postpartum women with a history of pre-eclampsia for features of the insulin resistance and the metabolic syndrome that are thought to contribute to endothelial dysfunction, and 2) Explore the relationships between insulin resistance and these identified features by evaluating for improvement in these abnormalities after insulin resistance is ameliorated with an insulin sensitizing agent. A cross-sectional study, designed to examine specific aim 1, will address the hypothesis that postpartum women with a history of pre-eclampsia are insulin resistant and have features of the metabolic syndrome (central adiposity, dyslipidemia, elevated cardiac output, and decreased endothelial dependent vasodilation) as compared to women without a history of pre-eclampsia. A double-blind, placebo-controlled randomized study will address the second hypothesis using an insulin sensitizing agent, rosiglitazone, in a 6 month cross-over study with measurements at baseline, 6 months, and 12 months.