Premium
Heritability and genetic correlations of insulin sensitivity measured by the euglycaemic clamp
Author(s) -
RasmussenTorvik L. J.,
Pankow J. S.,
Jacobs D. R.,
Steffen L. M.,
Moran A. M.,
Steinberger J.,
Sinaiko A. R.
Publication year - 2007
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2007.02271.x
Subject(s) - insulin resistance , heritability , insulin , endocrinology , medicine , glucose clamp technique , population , clamp , insulin sensitivity , biology , genetics , mechanical engineering , clamping , environmental health , engineering
Aims Studies investigating genetic factors influencing insulin sensitivity/insulin resistance have measured this phenotype using a variety of methods. In this study, genetic correlations and heritability of insulin sensitivity measured using the euglycaemic hyperinsulinaemic clamp and related phenotypes were examined. Methods The study population included 818 non‐diabetic individuals from 297 nuclear families. Genetic correlations and heritability estimates were calculated using variance components methods. Results Homeostasis model of insulin resistance (HOMA‐IR) and fasting insulin were very highly phenotypically and genetically correlated ( r = 0.99 and r = 0.99). HOMA‐IR and insulin sensitivity measured with the euglycaemic clamp were only moderately genetically correlated ( r = – 0.53), suggesting that the two traits may be influenced, at least in part, by different genes. Heritabilities for fasting insulin ( h 2 = 0.36) and HOMA‐IR ( h 2 = 0.38) were consistent with the published literature, but heritability for insulin sensitivity measured by the euglycaemic clamp was slightly lower than other published estimates ( h 2 = 0.24). Conclusions Because HOMA‐IR (or fasting insulin) and insulin sensitivity measured with the euglycaemic clamp are not highly genetically correlated, they should not be used interchangeably in genetic studies. Given the very high correlations between fasting insulin and HOMA‐IR, HOMA‐IR does not offer any advantage over fasting insulin in analyses of insulin sensitivity in this population.