Minimal Model–Based Insulin Sensitivity Has Greater Heritability and a Different Genetic Basis Than Homeostasis Model Assessment or Fasting Insulin

Insulin resistance is an important risk factor for devel-opment of type 2 diabetes as well as other chronic conditions, including hypertension, cardiovascular dis-ease, and colon cancer. To find genes for insulin resis-tance it is necessary to assess insulin action in large populations. We have previously measured insulin ac-tion 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 [SI]) with the measure of insulin resistance ema-nating from the homeostasis model assessment (HOMA) approach. The former measure emerges from the glyce-mic response to endogenous and exogenous insulin; the latter is based solely on fasting measures of glucose an