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Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans
Author(s) -
Goodarzi Mark O.,
Langefeld Carl D.,
Xiang Anny H.,
Chen YiiDer I.,
Guo Xiuqing,
Hanley Anthony J. G.,
Raffel Leslie J.,
Kandeel Fouad,
Nadler Jerry L.,
Buchanan Thomas A.,
Norris Jill M.,
Fingerlin Tasha E.,
Lorenzo Carlos,
Rewers Marian J.,
Haffner Steven M.,
Bowden Donald W.,
Rich Stephen S.,
Bergman Richard N.,
Rotter Jerome I.,
Watanabe Richard M.,
Wagenknecht Lynne E.
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20639
Subject(s) - insulin sensitivity , insulin , medicine , correlation , endocrinology , genetic correlation , sensitivity (control systems) , insulin resistance , genetic variation , environmental health , population , geometry , mathematics , electronic engineering , engineering
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 ( S I ), 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 ( S I , 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 S I 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 S I 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 S I suggest common genetic determinants.