Génétique du diabète de type 2: comment évaluer l’héritabilité de la capacité sécrétoire de la cellule β ?

Abstract

Aims/hypothesis

The aim of this study was to estimate the heritability of the beta-cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine.

Methods

This was a twin-family study that included 54 families from the Netherlands Twin Register. The participants were healthy twin pairs and their siblings of the same sex, aged 20–50 years. Insulin response of the beta cell was assessed by a modified hyperglycemic clamp with GLP-1 and arginine. Insulin sensitivity index (ISI) was assessed by the euglycemic-hyperinsulinemic clamp. Multivariate structural equation modeling was used to obtain heritabilities and the genetic factors underlying individual differences in BMI, ISI, and secretory responses of the beta cell.

Results

The heritability of insulin levels in response to glucose was 52 and 77% for the first and second phase, respectively, 53% in response to glucose + GLP-1, and 80% in response to an additional arginine bolus. Insulin responses to the administration of glucose, glucose + GLP-1, and glucose +GLP-1 + arginine were highly correlated (0.62 < R < 0.79). Heritability of BMI and ISI was 74 and 60%, respectively. The genetic factors that influenced BMI and ISI explained about half of the heritability of insulin levels in response to the three secretagogues. The other half was due to genetic factors specific to the beta cell.

Conclusions/Interpretation

In healthy adults, genetic factors explain most of the individual differences in the secretory capacity of the beta cell. These genetic influences are partly independent from the genes that influence BMI and ISI.