Genetic underpinnings of fasting and oral glucose-stimulated based insulin sensitivity indices.
J Clin Endocrinol Metab
; 2024 Apr 18.
Article
em En
| MEDLINE
| ID: mdl-38635292
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, OGTT0,120 and OGTT0,30,120 indices, using fasting and oral glucose tolerance test (OGTT) data in two 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=5,343), 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 OGTT0,30,120 indices had high genetic (ρG) and phenotypic (ρP) pairwise correlations (ρG and ρP 0.88 to 1) The OGTT0,120 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 was associated only with fasting indices, and PIK3R rs4976033 only with OGTT0,30,120 indices. The variants in FAM63A/MINDY1, GCK, C2CD4A/B, and FTO loci were associated only with OGTT0,120 indices.CONCLUSION:
Even though the IS indices mostly share a common genetic background, notable differences emerged between OGTT0,120 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2024
Tipo de documento:
Article