PATHOGENESIS OF INSULIN RESISTANCE AND HEPATIC STEATOSIS IN PATIENTS WITH

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。有证据表明，HCV患者的糖尿病患病率高于一般人群。肝脏脂肪沉积是肝硬化进展的一个危险因素，与基因型1相比，基因型3的肝脏脂肪沉积增加。肝脏和身体对葡萄糖的利用受损似乎会导致脂肪沉积和血液中炎症物质的增加。具体目的和程序：通过口服葡萄糖耐量试验，比较不同类型HCV患者的糖尿病发病倾向及其年龄、性别、BMI与正常健康志愿者相匹配的情况。2. 测定不同类型HCV患者在细胞水平上的脂肪沉积程度、结构和蛋白质变化，并与无基础肝病的UTMB手术患者“对照”肝脏标本进行比较。3)比较不同类型HCV患者和匹配的健康志愿者血液中炎症物质的水平。使用基因分析来观察炎症物质的分布，通过基因芯片与正常对照进行比较。将招募40名初次接受治疗的HCV患者和多达40名健康志愿者。第1组（N=20）：基因型为1的HCV患者，第2组（N=20）：基因型为3的HCV患者，第3组（N20）：无肝脏疾病的健康志愿者。这项研究将帮助我们了解慢性HCV患者糖尿病患病率较高的主要因素，也将告诉我们为什么基因型为3的HCV患者的肝脏脂肪比基因型为1的HCV患者多。

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. Evidence demonstrates that the prevalence of diabetes is greater in HCV patients than in the general population. Fat deposition in the liver is a risk factor for progression to cirrhosis and increased fat deposition in liver is seen genotype-3 compared to genotype-1. Impaired use of glucose by liver and the body seems to cause fat deposition and increased inflammatory substances in the blood. Specific Aims and Procedures: 1. To compare tendency to develop diabetes in different types of HCV patients and their age, gender, and BMI matched normal healthy volunteers by using oral glucose tolerance test. 2. To determine degree of fat deposition, structural and protein changes at cellular level in different types of HCV patients and compare with "controlled" liver specimens from the UTMB surgical patients without underlying liver diseases 3) To compare blood levels of inflammatory substances in different types of HCV patients and matched healthy volunteers. To use gene analysis to look at the inflammatory substance profiles compared to normal controls by using gene chips. 40 treatment naive HCV patients and up to 40 healthy volunteers will be enrolled. Arm 1 (N=20): HCV patients with genotype 1 Arm 2 (N=20): HCV patients with genotype 3 Arm 3 (N20): Healthy volunteers without liver diseases This study will help us understand the predominant factors responsible for higher prevalence of diabetes in patients with chronic HCV and also will tell us why patients with HCV genotype 3 have more fat in liver than genotype-1.