3. Hepatic insulin sensitivity and glucose metabolism: Because fat infiltration of liver and muscle causes insulin resistance and impairs glucose tolerance, we will measure parameters of metabolic control including fasting plasma glucose, free fatty acids, fructosamine, HbA1c and fasting lipid profile. To assess the effect of pioglitazone on hepatic insulin sensitivity, fasting (basal) and postprandial hepatic glucose production will be studied using a double-tracer technique (infusion of 3-3H glucose combined with an oral glucose load radiolabeled with 1-14C glucose) (23). Glucose and lipid oxidation will be measured by indirect calorimetry (24). In addition, an index of hepatic and peripheral insulin sensitivity will be derived from the oral glucose tolerance test (OGTT) (25).