Marian L Yurchishin, Lauren A Fowler, Amy M Goss, William T Garvey, Barbara A Gower
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引用次数: 0
摘要
研究目的研究目的是确定胰岛素抵抗(IR)遗传风险评分(GRS)与胰岛素敏感性指标之间的关联是否因种族和/或体重指数状况而异,研究对象为非裔美国人(AA)和无糖尿病的欧洲裔美国人(EA)成年人:以样本中位数(25.9 kg/m2)为切点,将 53 名 AA 和 54 名 EA 参与者分为 "高 "或 "低 "BMI 组。GRS是从之前确定的52个基因变异中得出的。骨骼肌胰岛素敏感性通过高胰岛素血糖钳夹法进行测量。胰岛素抵抗稳态模型评估(HOMA-IR)和松田胰岛素敏感性指数是根据口服葡萄糖耐量试验值计算得出的,分别用于确定肝脏和全身的胰岛素敏感性。按种族分层的线性回归模型评估了体重指数状况和胰岛素敏感性测量值之间的相互作用:结果:在 EA 参与者中,GRS 与 HOMA-IR 和松田指数的关系因 BMI 状态而异,其中只有高 BMI 组的 GRS 与 IR 相关。在 AA 参与者中,夹钳的关联因 BMI 状态而异,但只在低 BMI 组中观察到关联:这些结果凸显了IR的异质性,并支持了IR遗传易感性与肥胖之间的关系具有种族和组织特异性的假设。
Predictability of genetic risk score for insulin resistance is influenced by both BMI and race.
Objective: The study objective was to determine whether associations between a genetic risk score (GRS) for insulin resistance (IR) and measures of insulin sensitivity differ by race and/or BMI status in African American (AA) and European American (EA) adults without diabetes.
Methods: Fifty-three AA and 54 EA participants were classified into "high" or "low" BMI groups using the sample median (25.9 kg/m2) as the cut point. The GRS was derived from 52 previously identified genetic variants. Skeletal muscle insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index of insulin sensitivity were calculated from oral glucose tolerance test values to determine hepatic and whole-body insulin sensitivity, respectively. Linear regression models, stratified by race, assessed interactions between BMI status and GRS on measures of insulin sensitivity.
Results: In EA participants, associations of GRS with HOMA-IR and the Matsuda index differed by BMI status, where the GRS was associated with IR in the high-BMI group only. In AA participants, associations from the clamp differed by BMI status, but an association was observed only in the low-BMI group.
Conclusions: These results highlight the heterogeneity of IR and support the hypothesis that the relationship between genetic predisposition for IR and obesity is race- and tissue-specific.