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Genetic Underpinnings of Fasting and Oral Glucose-stimulated Based Insulin Sensitivity Indices.
- Source :
- Journal of Clinical Endocrinology & Metabolism; Nov2024, Vol. 109 Issue 11, p2754-2763, 10p
- Publication Year :
- 2024
-
Abstract
- Context Insulin sensitivity (IS) is an important factor in type 2 diabetes (T2D) and can be estimated by many different indices. Objective We aimed to compare the genetic components underlying IS indices obtained from fasting and oral glucose-stimulated plasma glucose and serum insulin levels. Methods We computed 21 IS indices, classified as fasting, OGTT<subscript>0,120</subscript>, and OGTT<subscript>0,30,120</subscript> indices, using fasting and oral glucose tolerance test (OGTT) data in 2 cohorts. We used data from a family cohort (n = 313) to estimate the heritability and the genetic and phenotypic correlations of IS indices. The population cohort, Inter99 (n = 5343), was used to test for associations between IS indices and 426 genetic variants known to be associated with T2D. Results Heritability estimates of IS indices ranged between 19% and 38%. Fasting and OGTT<subscript>0,30,120</subscript> indices had high genetic (ρG) and phenotypic (ρP) pairwise correlations (ρG and ρP: 0.88 to 1) The OGTT<subscript>0,120</subscript> indices displayed a wide range of pairwise correlations (ρG: 0.17-1.00 and ρP: 0.13-0.97). We identified statistically significant associations between IS indices and established T2D-associated variants. The PPARG rs11709077 variant was associated only with fasting indices and PIK3R rs4976033 only with OGTT<subscript>0,30,120</subscript> indices. The variants in FAM63A/MINDY1 , GCK , C2CD4A/B , and FTO loci were associated only with OGTT<subscript>0,120</subscript> indices. Conclusion Even though the IS indices mostly share a common genetic background, notable differences emerged between OGTT<subscript>0,120</subscript> indices. The fasting and OGTT-based indices have distinct associations with T2D risk variants. This work provides a basis for future large-scale genetic investigations into the differences between IS indices. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0021972X
- Volume :
- 109
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Journal of Clinical Endocrinology & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 180267700
- Full Text :
- https://doi.org/10.1210/clinem/dgae275