Bergman Richard N, Zaccaro Daniel J, Watanabe Richard M, Haffner Steven M, Saad Mohammed F, Norris Jill M, Wagenknecht Lynne E, Hokanson James E, Rotter Jerome I, Rich Steven S
Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Diabetes. 2003 Aug;52(8):2168-74. doi: 10.2337/diabetes.52.8.2168.
Insulin resistance is an important risk factor for development of type 2 diabetes as well as other chronic conditions, including hypertension, cardiovascular disease, and colon cancer. To find genes for insulin resistance it is necessary to assess insulin action in large populations. We have previously measured insulin action in a large cohort of subjects (Insulin Resistance and Atherosclerosis Study [IRAS] Family Study) using the minimal model approach. In this study, we compare sensitivity from the minimal model (insulin sensitivity index [S(I)]) with the measure of insulin resistance emanating from the homeostasis model assessment (HOMA) approach. The former measure emerges from the glycemic response to endogenous and exogenous insulin; the latter is based solely on fasting measures of glucose and insulin. A total of 112 pedigrees were represented, including 1,362 individuals with full phenotypic assessment. Heritability of S(I) was significantly greater than that for HOMA (0.310 vs. 0.163) and for fasting insulin (0.171), adjusted for age, sex, ethnicity, and BMI. In addition, correlation between S(I) and either HOMA or fasting insulin was only approximately 50% accounted for by genetic factors, with the remainder accounted for by environment. Thus S(I), a direct measure of insulin sensitivity, is determined more by genetic factors rather than measures such as HOMA, which reflect fasting insulin.
胰岛素抵抗是2型糖尿病以及其他慢性疾病(包括高血压、心血管疾病和结肠癌)发生的重要危险因素。为了寻找胰岛素抵抗相关基因,有必要在大量人群中评估胰岛素作用。我们之前使用最小模型法在一大群受试者(胰岛素抵抗与动脉粥样硬化研究[IRAS]家族研究)中测量了胰岛素作用。在本研究中,我们将最小模型的敏感性(胰岛素敏感性指数[S(I)])与源自稳态模型评估(HOMA)方法的胰岛素抵抗测量值进行比较。前者的测量值源自对内源性和外源性胰岛素的血糖反应;后者仅基于空腹血糖和胰岛素测量值。总共代表了112个家系,包括1362名进行了全面表型评估的个体。经年龄、性别、种族和体重指数调整后,S(I)的遗传力显著高于HOMA(分别为0.310和0.163)以及空腹胰岛素(0.171)。此外,S(I)与HOMA或空腹胰岛素之间的相关性仅约50%由遗传因素解释,其余部分由环境因素解释。因此,S(I)作为胰岛素敏感性的直接测量指标,更多地由遗传因素决定,而非像HOMA这样反映空腹胰岛素的指标。