INS VNTR is a QTL for the insulin response to oral glucose in obese children

We performed a genotype-phenotype association study to examine whether the insulin VNTR (INS VNTR) polymorphism located in the insulin gene promoter was associated with changes in insulin response to oral glucose. Two classes of INS VNTR alleles are observed in Caucasians, the "short" class I and the "long" class III. Plasma insulin and glucose concentrations and indices of insulin secretion (IGI) and sensitivity (ISI) were measured using an oral glucose tolerance test (OGTT) in 387 obese children aged 12 ± 0.1 yr with a mean body mass index (BMI) of 30.6 kg/m² (161% of the normal mean). During OGTT, plasma insulin and IGI were 20-30% higher in I/I obese children vs. III carriers (P < 0.01). A general linear model adjusting for age, sex, and puberty was also used to evaluate the influence of the VNTR genotype on the BMI-IGI (P = 0.07) and the BMI-ISI (P < 0.006) relationships. The INS VNTR can therefore be considered a quantitative trait locus influencing glucose-stimulated insulin physiology in obese juveniles.