Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans
MO Goodarzi, CD Langefeld, AH Xiang, YDI Chen… - …, 2014 - Wiley Online Library
MO Goodarzi, CD Langefeld, AH Xiang, YDI Chen, X Guo, AJG Hanley, LJ Raffel, F Kandeel…
Obesity, 2014•Wiley Online LibraryObjective 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 …
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 …
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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