Insulin Resistance in HCV Infection

描述(由申请人提供)： 这项建议的总体目标是支持首席研究员在专注于以患者为导向的研究的职业生涯中的发展。这个应用程序既有培训部分，也有科学部分。培训部分包括临床研究硕士学位的课程工作以及为职业发展提供坚实的赞助结构。科学部分整合了多学科方法，以评估丙型肝炎(丙型肝炎)感染对慢性丙型肝炎患者胰岛素作用的影响。流行病学研究表明，丙型肝炎病毒与2型糖尿病(DM)存在关联。而2型糖尿病则以胰岛素抵抗为特征。因此，丙型肝炎病毒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)。丙型肝炎病毒还会引起肝脏脂肪变性，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丙型肝炎患者脂肪变性的一个原因，这可能会恶化肝脏疾病的结局，这一点非常重要。这项研究的具体目的是： 1.研究非糖尿病合并丙型肝炎患者胰岛素敏感性和胰岛素分泌的变异性。 2.探讨丙型肝炎病毒感染者脂肪变性程度与胰岛素抵抗程度的相关性。 3.确定根除丙型肝炎病毒对胰岛素抵抗和胰岛素分泌的影响。 4.成功根除丙型肝炎病毒后，胰岛素敏感性的变化与肝脏脂肪变性的变化相关。 前瞻性队列设计将用于评估门诊丙型肝炎患者的人群。胰岛素抵抗、胰岛素分泌功能、血脂和脂蛋白谱将使用特定的方法进行评估。胰岛素敏感性/胰岛素抵抗的参数将与与丙型肝炎病毒相关的宿主和病毒因素进行比较，以努力确定可能是原因的特定因素。最后，因为我们认为丙型肝炎病毒和胰岛素抵抗之间的联系是有原因的，我们预计丙型肝炎病毒的成功治疗将导致胰岛素敏感性的改善和肝脏脂肪变性的减少。这项研究的一个重要优点是，将在丙型肝炎治疗前后对患者进行评估。这将允许直接评估丙型肝炎病毒在促进胰岛素抵抗和肝脏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.