EFFECT OF HIV-1 PROTEASE INHIBITORS ON ENDOTHELIAL FUNCTION AND GLUCOSE

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 本研究的总体目标是证明HIV-1蛋白酶抑制剂（PI）对血管内皮功能和糖脂代谢的影响会对心血管危险因素产生不利影响，本研究将在健康志愿者中进行探索性分析，以避免其他抗逆转录病毒药物的混杂作用和HIV感染本身。将PI药物引入常规临床实践中，导致HIV相关死亡率和机会性感染前所未有的降低，但与葡萄糖和脂质代谢的显著异常以及体脂分布的改变相关。 我们将研究10名非肥胖、非高血压、非糖尿病、HIV阴性的受试者。所有人都是健康的，年龄在20到50岁之间，没有怀孕，也没有服用任何药物。受试者将接受2次研究，一次在PI茚地那韦给药前，另一次在PI茚地那韦给药28-30天结束时。高血糖钳夹技术测定胰岛素分泌和全身葡萄糖摄取.将通过侵入性股动脉测量评价内皮依赖性和非内皮依赖性血流。 将比较基线和28-30天评价之间的以下变量：空腹血糖、胰岛素、c肽、全身葡萄糖处置率、高血糖期间的稳态胰岛素分泌、总胆固醇、LDL胆固醇、HDL胆固醇、甘油三酯、游离脂肪酸和分级药物输注后LBF的变化。还将进行葡萄糖和脂质代谢指标与内皮功能指标之间的相关性研究。

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 overall objective of this proposal is to demonstrate that HIV-1 protease inhibitors (PI) will adversely affected cardiovascular risk factors due their effects on endothelial function and glucose and lipid metabolism.This exploratory analysis will be done in healthy volunteers so that it is free from the confounding effects of other antiretroviral drugs and from HIV infection itself. The introduction of PI drugs into routine clinical practice has resulted in unprecedented reductions in HIV-related mortality and opportunistic infections, but has been associated with marked abnormalities in glucose and lipid metabolism and alterations in body fat distribution. We will study 10 non obese, non hypertensive, non diabetic, HIV-negative subjects. All will be healthy, between the ages of 20 and 50 years, not pregnant, and not ingesting any drugs. Subjects will be studied on 2 occasions, once before and again at the end of 28-30 days of administration of the PI indinavir. Insulin secretion and whole- body glucose uptake will measured by the hyperglycemic clamp technique. Endothelium dependent and independent blood flow will be evaluated by invasive femoral arterial measurements. The following variables will compare between the baseline and 28-30 day evaluations: Fasting plasma glucose, insulin, c-peptide, whole-body glucose disposal rate, steady-state insulin secretion during hyperglycemia, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, free fatty acids, and changes in LBF in response to the graded drug infusion. Correlations between measures of glucose and lipid metabolism and measures of endothelial function will also be performed.