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Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study
Authors:Hong Y,Weisnagel S J,Rice T,Sun G,Mandel S A,Gu C,Rankinen T,Gagnon J,Leon A S,Skinner J S,Wilmore J H,Bergman R N,Bouchard C,Rao D C  HERITAGE Family Study
Affiliation:Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA,;Division of Kinesiology, Department of Social and Preventive Medicine,;Diabetes Research Unit, Laval University, Ste-Foy, Québec, Canada,;Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA,;Laboratory of Molecular Endocrinology, CHUL Research Center, Ste-Foy, Québec, Canada,;School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, MN,;Department of Kinesiology, Indiana University, Bloomington, IN,;Department of Health and Kinesiology, Texas A&M University, College Station, TX,;Departments of Genetics and Psychiatry, University of Southern California, Los Angeles, CA, and;Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
Abstract:Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (SI) 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 (Kg), an overall index for glucose tolerance, acute insulin response to glucose (AIRGlucose) which is an index for insulin secretion, and those derived from the minimal model including SI and the disposition index (DI). DI, derived as the product of SI and AIRGlucose, 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 Kg, 44±14% (46±8%) for AIRGlucose, 38±12% (44±8%) for SI 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.
Keywords:heritability    insulin sensitivity    IVGTT    MINMOD    type 2 diabetes mellitus
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