Determinants of Whole-Body Protein Metabolism in Subjects With and Without Type 2 Diabetes

Abstract

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 15N-glycine method. Nitrogen flux was determined from urinary 15N 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 ln homeostasis model assessment of insulin resistance (HOMA-IR) explained 40% of the variance in flux in type 2 diabetes; fat-free mass and lnHOMA-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.