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Published online October 16, 2007
Diabetes 57:56-63, 2008
DOI: 10.2337/db07-0887
© 2008 by the American Diabetes Association
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Insulin Resistance of Protein Metabolism in Type 2 Diabetes

Sandra Pereira, Errol B. Marliss, José A. Morais, Stéphanie Chevalier, and Réjeanne Gougeon

McGill Nutrition and Food Science Centre, McGill University Health Centre/Royal Victoria Hospital, Montreal, Quebec, Canada

Address correspondence and reprint requests to Réjeanne Gougeon, McGill Nutrition and Food Science Centre, MUHC/Royal Victoria Hospital, 687 Pine Ave. West, H6.61, Montreal, QC H3A 1A1, Canada. E-mail: rejeanne.gougeon{at}muhc.mcgill.ca

Key Words: {alpha}-KIC, {alpha}-ketoisocaproic acid • BCAA, branched-chain amino acid • FFA, free fatty acid • FFM, fat-free mass • HOMA-IR, homeostasis model assessment of insulin resistance • REE, resting energy expenditure

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

RESEARCH DESIGN AND METHODS—Hyperinsulinemic (~570 pmol/l), euglycemic (5.5 mmol/l), and isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic type 2 diabetic subjects and 23 subjects without diabetes matched for age and body composition, after 7 days on a inpatient, protein-controlled, isoenergetic diet. Glucose and leucine kinetics were determined using tracers.

RESULTS—In type 2 diabetes, postabsorptive (baseline) glycemia was 8–9 mmol/l, glucose production (Ra) and disposal (Rd) were elevated, and once clamped, endogenous glucose Ra remained greater and Rd was less (P < 0.05) than in control subjects. 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 type 2 diabetic men, although protein breakdown decreased equally (~20%) in male groups but less in female groups. Whereas protein synthesis increased in male control subjects and in both female groups, it did not in male subjects with type 2 diabetes. In men, homeostasis model assessment of insulin resistance predicted 44%, and, in women, waist-to-hip ratio predicted 40% of the change in synthesis.

CONCLUSIONS—During our clamp, men with type 2 diabetes 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.


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