Mentored Patient-Oriented Research Career Development Aw

提案（改编自申请人摘要）：艾滋病毒感染者的治疗 患有PI的个体与身体脂肪分布的变化有关， 代谢紊乱与X综合征相似。 PI的使用已经 与高胰岛素血症相关的胰岛素抵抗，包括 糖尿病和向心性肥胖的发展， 伴随着四肢和臀部脂肪的减少。 目前还不清楚 这些并发症是如何相互关联的 经验的基础上 X综合征患者，如果这些代谢性疾病 PI治疗的并发症集群，那么他们将反过来与 增加患冠状动脉疾病的风险 这个提议的一个假设是 那些腹围增大的病人 发生高甘油三酯血症而身体无临床明显变化的患者 脂肪分布会有更多的内脏脂肪和胰岛素 与对照组相比， 研究人员推测， 变化代表一种综合征，而不是几种综合征。 为了验证这个假设， 将比较四组HIV感染受试者：1）PI治疗的患者 2）PI治疗的患者， 高脂血症，但无临床上明显的体脂变化 3）PI治疗的患者无这两种并发症;和 4)PI初治患者。 身体成分和内脏肥胖将是 通过双能X射线吸收测定法（DEXA）和计算机化 断层扫描，分别。 胰岛素敏感性将使用 频繁采样静脉葡萄糖试验（FSIGT）。 一项前瞻性研究是 还计划检验以下假设：在开始PI治疗后， 胰岛素敏感性的下降将预示着内脏脂肪的发展 积累，因此，在其发展中可能是偶然的。 这是一 研究内脏肥胖的发展及其 与胰岛素抵抗的关系 最后，研究人员假设 与PI治疗相关的外周脂肪组织减少， 由于甘油三酯（TG）的动员增加或储存减少， 那些仓库 脂肪组织损失的其他潜在机制包括 还将研究细胞凋亡和去分化。 外围设备的丢失 脂肪储存提供了一个独特的机会，以确定基因参与， 调节脂肪组织的质量和分布。

PROPOSAL (Adapted from the applicant's abstract): Treatment of HIV-infected individuals with PIs is associated with changes in body fat distribution and metabolic disturbances similar to those seen in syndrome X. PI use has been variably associated with hypertriglyceridemia, insulin resistance including diabetes mellitus and the development of central obesity which is often accompanied by loss of fat from the extremities and buttocks. It is unclear how these complications relate to each other. Based on the experience of patients with syndrome X, it is highly probable that if these metabolic complications of PI therapy cluster, then they will in turn be associated with an increased risk of coronary artery disease. One hypothesis of this proposal is that patients who develop an increase in abdominal girth as well as those who develop hypertriglyceridemia without a clinically apparent change in body fat distribution will both have significantly more visceral fat and insulin resistance compared to controls. The investigators hypothesize that these changes represent one syndrome rather than several. To test this hypothesis, four groups of HIV-infected subjects will be compared: 1) PI-treated patients who have developed a "protease paunch;" 2) PI-treated patients with hypertriglyceridemia but no clinically apparent change in body fat distribution; 3) PI-treated patients free of these two complications; and 4) PI-naive patients. Body composition and visceral adiposity will be determined by dual energy X-ray absorptiometry (DEXA) and computerized tomography, respectively. Insulin sensitivity will be measured using the frequently sampled intravenous glucose test (FSIGT). A prospective study is also planned to test the hypothesis that, after the initiation of PI therapy, a decline in insulin sensitivity will predict the development of visceral fat accumulation and, therefore, may be casual in its development. This is a unique opportunity to study the development of visceral obesity and its relationship to insulin resistance. Finally, the investigators hypothesize that the decrease in peripheral adipose tissue associated with PI therapy is due to increased mobilization or decreased storage of triglycerides (TGs)in those depots. Other potential mechanisms of adipose tissue loss including apoptosis and dedifferentiation will also be studied. The loss of peripheral fat stores offer a unique opportunity to determine the genes involved in regulating adipose tissue mass and distribution in general.