Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin
Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin
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DOI：
10.2337/diabetes.52.8.2168
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发表时间：
2003-08-01
期刊：
影响因子：
7.7
通讯作者：
Rich, SS
中科院分区：
文献类型：
--
作者：
Bergman, RN;Zaccaro, DJ;Rich, SS
胰岛素抵抗是2型糖尿病发生的重要危险因素。其他慢性疾病，包括高血压、心血管疾病和结肠癌。为了找到胰岛素抵抗的基因，有必要评估胰岛素在大人群中的作用。我们之前已经使用最小模型方法在一大群受试者(胰岛素抵抗和动脉粥样硬化研究[IRAS]家族研究)中测量了胰岛素作用。在这项研究中，我们比较了最小模型(胰岛素敏感性指数[S-I])和稳态模型评估(HOMA)方法得出的胰岛素抵抗的敏感性。前者来自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的测量。总共有112个家系，包括1362个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的遗传度显著高于HOMA(0.310比0.163)和空腹胰岛素(0.171)。此外，S-I与HOMA和空腹胰岛素的相关性只有50%是遗传因素造成的，其余的是环境因素造成的。因此，直接衡量胰岛素敏感性的S-I指数更多地是由遗传因素决定的，而不是反映空腹胰岛素的HOMA等指标。
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, 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 similar to50% 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.