Effect of exogenous insulin on protein metabolism with differing nonprotein energy intakes in type 2 diabetes mellitus

OBJECTIVE: To determine if insulin treatment combined with a generous protein intake would normalize whole-body protein kinetics and nitrogen balance in obese subjects with Type 2 diabetes mellitus when compared to obese nondiabetic subjects: 1) during weight-maintenance and 2) after a very low energy diet (VLED). DESIGN: Clinical intervention study of iso- followed by hypoenergetic feedings with or without exogenous insulin. SUBJECTS: Sixteen obese subjects with a body mass index (BMI) of 39 +/- 4 kg/m(2), with Type 2 diabetes mellitus (three men, six women) or without (one man, six women). MEASUREMENTS: Nitrogen flux rate calculated from the urine N-15-urea enrichment by using the 60 h oral N-15-glycine method, rates of protein synthesis and breakdown calculated from nitrogen flux on days 6-8 (and 13-15 in the diabetic subjects) of isoenergetic feeding and days 24-26 of a 1.9 MJ diet. RESULTS: With insulin therapy: 1) during isoenergetic feeding, in the hyperglycaemic diabetic subjects, nitrogen balance was significantly less than in the obese controls (-0.6 +/- 0.6 compared with +1.8 +/- 0.9 g N/d, P = 0.037) but became positive (+2.6 +/- 0.6 g N/d, P < 0.05); nitrogen flux decreased and net protein synthesis increased from values different from those of the obese controls to values no longer different; 2) during the VLED, plasma glucose concentrations < 7 mmol/L were achieved and maintained in all diabetic subjects. Nitrogen equilibrium observed in five out of seven obese nondiabetic and four out of nine diabetic subjects was associated with no change in nitrogen flux from the euglycaemic isoenergetic studies, but with 17% and 23% lower rates of synthesis (P < 0.05) and 7% and 15% lower rates of breakdown (NS) in nondiabetic and diabetic subjects, respectively. CONCLUSION: Sufficient exogenous insulin to near-normalize glycaemia improves the altered protein metabolism in hyperglycaemic diabetic subjects during isoenergetic feeding, and restores nitrogen equilibrium better than with VLED alone. Protein metabolism is more sensitive to the state of diabetes control than is generally appreciated 'clinically'.