HEPATIC DRUG-METABOLISM IS INCREASED IN POORLY CONTROLLED INSULIN-DEPENDENT DIABETES-MELLITUS

In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t(1/2)) and metabolism: the mean antipyrine t(1/2) slowed from 4.7 ± 0.2 (SEM) initially to 7.8 ± 0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6 ± 1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.