An attempt to determine the role of insulin resistance in the development of non-alcoholic steatohepatitis (NASH). NASH is a condition characterized by deposits of sac-like fats within the cells of the liver. The causes of NASH are not known. However, an association between NASH and glucose intolerance has been established. A major part of the inability to metabolize sugar is the resistance to insulin. History has shown that 5-10% of patients who undergo liver biopsy have NASH symptoms. The true prevalence of the condition is unknown. Most patients with NASH have no symptoms and NASH comes to attention when patients have enlarged livers or elevated serum shown in blood tests done for liver function. A smaller percentage of patients have symptoms of chronic liver disease with fatigue, itching, swelling, accumulation of fluids, and liver failure. The presence of obesity can also be a clue. There is limited data on the history of NASH. Progression of the condition is generally slow. Many of the NASH patients have diabetes. It is felt that insulin resistance leads to the development of NASH. Until recently, it has not been possible to test the hypothesis that insulin resistance might play a role in the development of NASH. However, the development of a new class of insulin sensitizers offers an opportunity to do so. The study will examine the relationship between insulin resistance and NASH. Patients identified with NASH and age and sex-matched control subjects will be asked to participate in the study. They will be questioned about personal and family history of high blood pressure and cholesterol levels. Prior to the study each patient will be evaluated by the General Clinical Research Center nutritionist and body measurements and fat measurement will be taken. Each subject will be given a glucose tolerance test. The energy each subject uses over a 24 hour period will be calculated and insulin sensitivity will be determined. Frequent blood samples will be taken to assure a steady glucose level. A liver and skin biopsy will be performed, following which, the subjects will begin treatment with either troglitazone or a sugar pill taken daily for two years. Neither subject nor doctor will know which treatment each subject is taking. Each subject will visit the Clinical Research Center every three months for liver monitoring and resupplying of pills. At the two year mark, a final visit will determine the effect of the treatment on the liver.
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