Insulin resistance of protein metabolism in type 2 diabetes
Insulin resistance of protein metabolism in type 2 diabetes
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DOI：
10.2337/db07-0887
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发表时间：
2008-01-01
期刊：
影响因子：
7.7
通讯作者：
Gougeon, Rejeanne
中科院分区：
文献类型：
--
作者：
Pereira, Sandra;Marliss, Errol B.;Gougeon, Rejeanne
目的：我们先前证明：1)肥胖会损害蛋白质代谢的胰岛素敏感性，2)性别会影响蛋白质代谢的胰岛素敏感性，而3)2型糖尿病血糖控制不良会加速每日禁食状态下的蛋白质周转。研究设计与方法：对17例高血糖2型糖尿病患者和23例年龄和体成分相匹配的非糖尿病患者进行高胰岛素血症(类似于570Prnol/L)、正常血糖(5.5 mmoL/L)和异氨基酸血症(保持在吸收后浓度)钳夹治疗，7天后进行蛋白质控制的等能量饮食。结果：2型糖尿病患者吸收后血糖(基线)为8~9 mm ol/L，葡萄糖生成(R-a)和葡萄糖处置(R-d)均升高，阻断后内源性血糖R仍高于对照组，RD低于对照组(P<；0.05)。尽管胰岛素水平较高，但基线亮氨酸动力学没有差异。后者是男女之间亮氨酸流量的独立预测因子。使用钳夹，男性2型糖尿病患者的总流量增加较少(P=0.016)，但男性组的蛋白质分解降低了20%，而女性组的降解率较低。虽然男性对照组和两组女性的蛋白质合成都有所增加，但患有2型糖尿病的男性受试者却没有。在男性中，胰岛素抵抗的稳态模型评估预测了44%，而在女性中，腰臀比预测了40%的合成变化。结论-在我们的夹闭期间，男性2型糖尿病患者的蛋白质代谢胰岛素抵抗比过度肥胖本身导致的更大，而女性则不是。这些结果可能会对膳食蛋白质的需求产生影响。
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 (similar to 570 prnol/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. 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 (similar to 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.