A study to determine if HCV (hepatitis C virus) is a risk for insulin resistance leading to impaired glucose tolerance in chronic HCV patients. HCV is now recognized as one of the most common causes of chronic liver disease and cirrhosis in North America. Recently, a relationship between non-insulin dependent diabetes mellitus (NIDDM) and chronic HCV has been discovered. Several studies have shown a 15-20% prevalence of NIDDM in patients with HCV compared to 2-4% in age and sex matched control subjects. The causes of diabetes development in patients with HCV are not known. Almost all patients who have HCV who are diabetic have NIDDM which is associated with insulin resistance rather than decreased insulin production. It is well known that cirrhosis is associated with insulin resistance, impaired glucose tolerance, and NIDDM. However, in a large study, most of the patients with HCV and NIDDM did not have cirrhosis. In this proposal, the possibility that HCV infection leads to a state of insulin resistance which eventually leads to NIDDM will be tested. This study will have a test group and a control group and will be done in three phases. First will be the baseline studies where consents will be signed, clinical data will be obtained, and a liver biopsy will be done to determine the amount of inflammation and fibrosis of the liver. Amount of fatty liver will be scored. Second, initial studies will be done. Tests will be an oral glucose tolerance test, body fat measurement, nutritional evaluation, fasting venous insulin C peptide levels, and hormone levels. Then, an overnight fast will take place, a pill of glucose will be given, and insulin levels will be assessed. The third phase will be an evening meal and then fasting again until the metabolic studies are complete. The next morning, glucose will be measured along with specific hormones. The amount of glucose put out by the liver will be measured, blood samples will be obtained, energy expenditure will be measured, urine will be collected. Insulin sensitivity will be tested by infusing insulin and glucose at the same time and then blood tests will be done to assure steady glucose levels.
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