Mentored Patient-Oriented Research Career Development Aw

提案(改编自申请人的摘要)：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和 代谢紊乱类似于X综合征。使用PI一直是 与高甘油三酯血症相关，胰岛素抵抗包括 糖尿病和中心性肥胖症的发展 伴随着四肢和臀部脂肪的减少。目前还不清楚 这些复杂情况是如何相互关联的。基于以下经验： 患有X综合征的患者，如果这些新陈代谢 PI治疗集群的并发症，那么它们又会与 增加患冠状动脉疾病的风险。这一提议的一个假设 腹围增加的患者和那些 患有高甘油三酯血症而身体无明显临床改变的患者 脂肪分布会有更多的内脏脂肪和胰岛素 抵抗力与对照组相比。调查人员推测，这些 变化代表一种症状，而不是几种。为了检验这一假设， 四组HIV感染者将进行比较：1)接受PI治疗的患者 谁已经形成了“蛋白水解酶腹肌”；2)接受PI治疗的患者 高甘油三酯血症，但体脂无明显临床变化 分布；3)PI治疗的患者没有这两种并发症； 4)幼稚的病人。身体成分和内脏肥胖症 由双能X射线吸收法(DEXA)和计算机化测定 分别进行断层扫描。胰岛素敏感性将使用 频繁取样静脉血糖试验(FSIGT)。一项前瞻性研究是 还计划检验这样的假设，即在PI治疗开始后， 胰岛素敏感性下降将预示内脏脂肪的发展 因此，在其发展过程中可能是随意的。这是一个 研究内脏肥胖症及其发病机制的难得机会 与胰岛素抵抗的关系。最后，调查人员提出假设 与PI治疗相关的外周脂肪组织的减少 由于甘油三酯(TGS)在体内动员增加或储存减少 那些仓库。脂肪组织丢失的其他潜在机制包括 此外，还将研究细胞凋亡和去分化。外设的流失 脂肪储存提供了一个独特的机会来确定与 总体上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.