Drug Metabolism in Diabetic Subjects with Fatty Livers

The effect of fatty degeneration of liver parenchyma on drug metabolism was investigated in 21 obese non-insulin-dependent diabetic subjects by measuring plasma antipyrine kinetics, hepatic cytochrome P-450, liver size and the extent of fatty infiltration. The hepatic drug metabolising capacity, as measured by total antipyrine clearance and the estimated total amount of cytochrome P-450, was at the same level as in non-diabetic control subjects with normal livers. Relative antipyrine clearance (per unit weight of liver) and cytochrome P-450 concentrations were significantly lower in the diabetics than in controls. The extent of fatty infiltration correlated poorly with the indices of drug metabolism. In non-insulin-dependent diabetics, slight to moderate hepatic fatty infiltration, without more serious structural distortion interfering with hepatic blood flow or hepatocellular function, seems to have only a minor influence on drug metabolism.