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

HIV-1 蛋白酶抑制剂对内皮功能和血糖的影响

• 批准号: 7606379
• 负责人: MICHAEL P DUBE
• 金额: $ 26.87万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606379
• 关键词: Affect; Age; Anti-Retroviral Agents; Blood flow; Body fat; Cholesterol; Clinical; Computer Retrieval of Information on Scientific Projects Database; Endothelium; Evaluation; Fasting; Funding; Glucose; Grant; HIV Infections; HIV-1; High Density Lipoprotein Cholesterol; Hyperglycemia; Indinavir; Infusion procedures; Institution; Insulin; Invasive; LDL Cholesterol Lipoproteins; Lipids; Measurement; Measures; Non obese; Nonesterified Fatty Acids; Opportunistic Infections; Patient currently pregnant; Peptides; Pharmaceutical Preparations; Plasma; Protease Inhibitor; Rate; Research; Research Personnel; Resources; Source; Techniques; Triglycerides; United States National Institutes of Health; cardiovascular risk factor; day; glucose disposal; glucose uptake; healthy volunteer; insulin secretion; lipid metabolism; mortality; non-diabetic; response

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该提案的总体目的是证明HIV-1蛋白酶抑制剂（PI）将由于其对内皮功能以及葡萄糖以及葡萄糖和脂质代谢的影响而受到不利影响的心血管危险因素。这种探索性分析将在健康的志愿者中进行，因此它可以自由地从其他抗逆性药物和HIV Invection toctions and Invection from from the the the the wive效应。将PI药物引入常规临床实践已导致与HIV相关的死亡率和机会性感染的前所未有的降低，但与葡萄糖和脂质代谢的明显异常以及体内脂肪分布的改变有关。 我们将研究10个非肥胖，非高血压，非糖尿病，HIV阴性受试者。一切都将健康，年龄在20至50岁之间，不怀孕，也不会摄取任何药物。将在28-30天的PI Indinavir给药前和再次结束时进行两次研究对象。胰岛素分泌和全身葡萄糖摄取将通过高血糖夹技术测量。内皮依赖性和独立的血流将通过浸润性股动脉测量评估。 以下变量将在基线和28-30天评估之间进行比较：空腹血糖，胰岛素，C肽，全身葡萄糖处置率，高血糖期间稳态胰岛素分泌，总胆固醇，LDL胆固醇，HDL胆固醇，HDL胆固醇，trigysterol，trigysterol，trigysteries，trefty Artifty and tery Adicer，以及对LBF的变化。还将进行葡萄糖与脂质代谢的测量与内皮功能的度量之间的相关性。