Insulin resistance of protein metabolism in type 2 diabetes.
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.


METHODS
Hyperinsulinemic ( approximately 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 (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 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 ( approximately 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.
Pereira
Sandra
S
McGill Nutrition and Food Science Centre, MUHC/Royal Victoria Hospital, 687 Pine Ave. West, H6.61, Montreal, QC H3A 1A1, Canada.
Marliss
Errol B
EB
Morais
José A
JA
Chevalier
Stéphanie
S
Gougeon
Réjeanne
R
D000328:Adult; D000596:Amino Acids / Q000097:blood; D001774:Blood Chemical Analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005498:Follicular Phase; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D007930:Leucine / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D012016:Reference Values
D000596:Amino Acids; D007328:Insulin; D011506:Proteins; D007930:Leucine