Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (S_I) and insulin secretion. While a strong genetic component for T2DM is well established, there are few reports on racial differences in the magnitude of the genetic effects of T2DM and indices of glucose and insulin metabolism. We report here on the familial resemblance for traits related to glucose metabolism at pre-exercise training levels in 492 members from 99 sedentary White families and 259 members from 108 Black families participating in the multicenter HERITAGE Family Study. All these traits were obtained from the frequently sampled intravenous glucose tolerance test (IVGTT). They include glucose disappearance index (K_g), an overall index for glucose tolerance, acute insulin response to glucose (AIR_Glucose) which is an index for insulin secretion, and those derived from the minimal model including S_I and the disposition index (DI). DI, derived as the product of S_I and AIR_Glucose, is a measure of the activity of the B-cells adjusted for insulin resistance. After adjustment for age, sex, and body mass index, the maximal heritability estimates in Blacks (Whites) are 48 ± 14% (25 ± 8%) for K_g, 44 ± 14% (46 ± 8%) for AIR_Glucose, 38 ± 12% (44 ± 8%) for S_I and 32 ± 14% (24 ± 8%) for DI. Interestingly, Blacks have higher heritability for overall glucose tolerance than Whites but there is no race difference in heritability estimates for insulin sensitivity or insulin secretion.