Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans

Mark O. Goodarzi, Carl D. Langefeld, Anny H. Xiang, Yii Der I. Chen, Xiuqing Guo, Anthony J.G. Hanley, Leslie J. Raffel, Fouad Kandeel, Jerry L. Nadler, Thomas A. Buchanan, Jill M. Norris, Tasha E. Fingerlin, Carlos Lorenzo, Marian J. Rewers, Steven M. Haffner, Donald W. Bowden, Stephen S. Rich, Richard N. Bergman, Jerome I. Rotter, Richard M. WatanabeLynne E. Wagenknecht

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Objective The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). Methods GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components. Results Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI, M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P<0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P<0.0001); and -0.16 to -0.36 for AIRg and MCRI (P<0.0001-0.06). Conclusions These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.

Original languageEnglish (US)
Pages (from-to)1157-1164
Number of pages8
JournalObesity
Volume22
Issue number4
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Fingerprint Dive into the research topics of 'Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans'. Together they form a unique fingerprint.

  • Cite this

    Goodarzi, M. O., Langefeld, C. D., Xiang, A. H., Chen, Y. D. I., Guo, X., Hanley, A. J. G., Raffel, L. J., Kandeel, F., Nadler, J. L., Buchanan, T. A., Norris, J. M., Fingerlin, T. E., Lorenzo, C., Rewers, M. J., Haffner, S. M., Bowden, D. W., Rich, S. S., Bergman, R. N., Rotter, J. I., ... Wagenknecht, L. E. (2014). Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans. Obesity, 22(4), 1157-1164. https://doi.org/10.1002/oby.20639