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

rejeanne.gougeon{at}muhc.mcgill.ca

ABSTRACT

OBJECTIVE: Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes (T2DM) and obesity. We hypothesized that glycemia, insulin resistance and waist circumference modulate these alterations in T2DM and to a lesser extent in persons without T2DM.

RESEARCH DESIGN AND METHODS: In 88 lean and obese subjects without and 40 with T2DM on an inpatient protein-controlled isoenergetic diet for 7days, whole-body protein turnover was measured using the fed-fasted 60-hour oral ¹⁵N-glycine method. Nitrogen flux was determined from urinary ¹⁵N urea and protein synthesis, breakdown and net balance calculated. Indices of diabetes control, resting energy expenditure (REE) and body composition were assessed.

RESULTS: Higher protein turnover in the obese was further increased and net balance was lower in T2DM. Waist-to-hip ratio and lnHOMA-IR explained 40% of the variance in flux in T2DM; FFM and lnHOMA-IR 62% in subjects without T2DM. Overall, fasting glucose explained 16% of the variance in net balance. In T2DM, 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 T2DM, independently of obesity. Elevated flux is associated with greater visceral adiposity, REE and insulin resistance of glucose. In T2DM men, these alterations worsened with magnitude of hyperglycemia. In T2DM women, larger hip circumferences may protect against such alterations. Our findings suggest that dietary protein requirements may be greater in T2DM to offset a reduced net balance, aggravated as glycemia increases, especially in men.

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