Abstract

Objective: We previously demonstrated that 1) obesity impairs and 2) gender influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes (T2DM) accelerates protein turnover in daily fed-fasted states. We hypothesized that T2DM alters the insulin sensitivity of protein metabolism, and gender modulates it.

Research Design And Methods: Hyperinsulinemic, (∼570 pmol/L), euglycemic (5.5 mmol/L), isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic T2DM and 23 subjects without diabetes matched for age and body composition, after 7d inpatient, protein-controlled, isoenergetic diets. Glucose and leucine kinetics were determined using tracers.

Results: In T2DM, postabsorptive (baseline) glycemia was 8-9 mmol/L, glucose production (R_a) and disposal (R_d) were elevated, and once clamped, endogenous glucose R_a remained greater and R_d was less (P <0.05) than in controls. Baseline leucine kinetics did not differ despite higher insulin levels. The latter was an independent predictor of leucine flux within each sex. With clamp, total flux increased less (P = 0.016) in T2DM men, though protein breakdown decreased equally (∼20%) in male groups but less in female groups. Whereas protein synthesis increased in male controls and in both female groups, it did not in male T2DM. In men, HOMA-IR predicted 44%, whereas in women, waist-to-hip ratio predicted 40% of the change in synthesis.

Conclusions: During our clamp, men with T2DM have greater insulin resistance of protein metabolism than that conferred by excess adiposity itself, whereas women do not. These results may have implications for dietary protein requirements.