Determinants of whole-body protein metabolism in subjects with and without type 2 diabetes

OBJECTIVE - Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes and obesity. We hypothesized that glycemia, insulin resistance, and waist circumference modulate these alterations in type 2 diabetes and, to a lesser extent, in individuals without type 2 diabetes. RESEARCH DESIGN AND METHODS - In 88 lean and obese subjects without and 40 with type 2 diabetes on an inpatient protein-controlled isoenergetic diet for 7 days, whole-body protein turnover was measured using the fed-fasted 60-h oral N-15-glycine method. Nitrogen flux was determined from urinary N-15 urea and protein synthesis, breakdown and net balance calculated. Indexes of diabetes control, resting energy expenditure (REE), and body composition were assessed. RESULTS - Higher protein turnover in obese subjects was further increased and net balance, was lower in type 2 diabetes. Waist-to-hip ratio and In homeostasis model assessment of insulin resistance (HOMA-IR) explained 40% of the variance in flux in type 2 diabetes; fat-free mass and InHOMA-IR explained 62% in subjects without type 2 diabetes. Overall, fasting glucose explained 16% of the variance in net balance. In type 2 diabetes, net balance correlated negatively with fasting glucose in men and positively with hip circumference in women. CONCLUSIONS - Kinetics of whole-body protein metabolism are elevated, and net balance is diminished in type 2 diabetes, independently of obesity. Elevated flux is associated with greater visceral adiposity, REE, and insulin resistance of glucose. In type 2 diabetic men, these alterations worsened with magnitude of hyperglycemia. In type 2 diabetic women, larger hip circumferences may protect against such alterations. Our findings suggest that dietary protein requirements may be greater in type 2 diabetes to offset a reduced net balance, aggravated as glycemia increases, especially in men.