Leucine Metabolism in Type II Diabetes Mellitus

Abstract

Severe muscle wasting is a well-recognized characteristic of untreated insulin-deficient diabetes mellitus, a condition in which leucine turnover and oxidation are accelerated. To ascertain whether a similar circumstance exists in type II diabetes when insulin is present but with reduced efficacy, we investigated leucine turnover and oxidation in five obese type II diabetic women by tracer infusion of L-[1-13C,15N]leucine in the postabsorptive state both before and after intensive insulin therapy. With conventional treatment, the type II diabetic women received 61 ± 33 (SD) U/day of insulin, and their fasting plasma glucose averaged 194 ± 41 (SD) mg/dl. Leucine carbon flux (Qc), nitrogen flux (QN), and oxidation (C) averaged 6.4 ± 1.2,15.6 ± 4.6, and 1.4 ± 0.3 mmol/h, respectively. These values were not different from the respective values of 6.6 ± 1.3, 17.0 ± 8.3, and 1.0 ± 0.2 mmol/h in matched obese nondiabetic controls, suggesting that leucine metabolism is not altered in insulin-treated type II diabetics. After a week of intensive insulin therapy in which the same diabetic subjects received 94 ± 36 U/day of insulin, postabsorptive plasma glucose declined to 117 ± 26 mg/dl. Leucine Qc(6.2 ± 1.0), QN (14.8 ± 3.7), and C (1.5 ± 0.5 mmol/h) were unaltered by the increased insulin therapy. Thus, obese type II diabetics had normal leucine kinetics but were hyperglycemic while receiving conventional insulin therapy. Additional intensive insulin therapy in these diabetic subjects improved plasma glucose but did not alter leucine kinetics. Thus, these data demonstrate a differential sensitivity of insulin's action on carbohydrate versus amino acid metabolism in type II diabetics.