Insulin Resistance in HCV Infection

描述（由申请人提供）： 本提案的总体目标是支持主要研究者在以患者为导向的研究职业生涯中的发展。这一应用既有培训内容，也有科学内容。培训内容包括临床研究硕士课程以及职业发展的坚实赞助结构。科学部分整合了多学科方法，以评估丙型肝炎（HCV）感染对慢性HCV感染患者胰岛素作用的影响。流行病学研究表明，HCV与2型糖尿病（DM）之间存在关联。2型糖尿病的特点是胰岛素抵抗。因此，HCV感染可能促进组织对胰岛素介导的葡萄糖摄取的抵抗。胰岛素抵抗对肝脏疾病很重要，因为它会导致肝脏脂肪变性（脂肪肝）。HCV还引起肝脂肪变性，并与加速的肝纤维化有关。因此，确定胰岛素抵抗是否是慢性HCV感染患者脂肪变性的一个原因，这可能会恶化肝脏疾病的结果，这是非常重要的。这项研究的具体目标是： 1. 描述非糖尿病患者胰岛素敏感性和胰岛素分泌的变异性， HCV感染。 2.为了确定脂肪变性的严重程度和胰岛素抵抗程度之间的相关性， HCV感染者。 3.确定HCV根除对胰岛素抵抗和胰岛素分泌的影响。 4.将成功根除HCV后胰岛素敏感性的变化与肝脂肪变性的变化相关联。 前瞻性队列设计将用于评估门诊HCV人群。将使用特定方法评价胰岛素抵抗、胰岛素分泌功能、脂质和脂蛋白谱。胰岛素敏感性/胰岛素抵抗的参数将与HCV相关的宿主和病毒因素进行比较，以确定可能是因果关系的特定因素。最后，因为我们相信HCV和胰岛素抵抗之间的联系是因果关系，我们预期HCV的成功治疗将导致胰岛素敏感性的改善以及肝脏脂肪变性的减少。这项研究的一个重要优点是，患者将在HCV治疗前后进行评估。这将允许直接评价HCV在促进胰岛素抵抗和肝脂肪变性中的致病作用。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to support the principal investigator's development in a career focused on patient-oriented research. This application has both training and scientific components. The training component includes course work towards a Master's in Clinical Research as well as a solid sponsorship structure for career development. The scientific component integrates a multidisciplinary approach in order to assess the impact of hepatitis C (HCV) infection on insulin action in patients with chronic HCV infection. Epidemiological studies have shown that there is an association between HCV and type 2 diabetes mellitus (DM). Type 2 DM in turn, is characterized by insulin resistance. Thus, it is possible that HCV infection promotes tissue resistance to insulin-mediated glucose uptake. Insulin resistance is of importance to liver disease because it can lead to hepatic steatosis (fatty liver). HCV also causes hepatic steatosis, and is associated with accelerated hepatic fibrosis. Therefore, it is of great importance to determine whether insulin resistance represents a cause of steatosis in patients with chronic HCV infection that could worsen the outcome of liver disease. The specific aims of this study are: 1. To characterize the variability in insulin sensitivity and insulin secretion in non-diabetic patients with HCV infection. 2. To determine the correlation between severity of steatosis and the degree of insulin resistance in HCV-infected individuals. 3. To determine the effect of HCV eradication on insulin resistance and insulin secretion. 4. To correlate changes in insulin sensitivity with changes in hepatic steatosis after successful HCV eradication. A prospective cohort design will be used to assess an outpatient HCV population. Insulin resistance, insulin secretory function, lipid and lipoprotein profiles will be evaluated using specific methodologies. Parameters of insulin sensitivity/insulin resistance will be compared to host and viral factors associated with HCV, in an effort to identify specific factors that may be causal. Finally, because we believe that the connection between HCV and insulin resistance is causal, we anticipate that successful treatment of HCV will result in improved insulin sensitivity together with a reduction in hepatic steatosis. One of the important advantages of this study is that patients will be evaluated before and after HCV treatment. This will permit a direct evaluation of the causative role of HCV in promoting insulin resistance and hepatic steatosis.