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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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