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Multicenter Study
. 2014 Apr;22(4):1157-64.
doi: 10.1002/oby.20639.

Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans

Mark O Goodarzi  1 , 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 Watanabe, Lynne E Wagenknecht
Affiliations
Multicenter Study

Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans

Mark O Goodarzi et al. Obesity (Silver Spring). 2014 Apr.

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.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors have no competing interests relevant to this study.

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