Utility of early insulin response and proinsulin to assess insulin resistance.

Objective: To determine whether obesity and premature adrenarche are additive events increasing the risk of insulin resistance and beta-cell failure, using early insulin response (EIR) or the insulinogenic index and proinsulin (PI) as markers.

Study Design: This was a prospective case-control study conducted at a tertiary care academic medical center involving 81 prepubertal, predominantly Hispanic children (34 males, 47 females), classified as lean controls (4 males, 6 females; mean age, 6.5 +/- 1.2 years; mean body mass index [BMI] z-score, 0.08 +/- 0.6), obese controls (20 males, 10 females; mean age, 7.2 +/- 1.5 years; mean BMI z-score, 2.5 +/- 0.5), lean premature adrenarche (3 males, 11 females; mean age, 7.1 +/- 1.2 years; mean BMI z-score, 0.09 +/- 0.6), and obese premature adrenarche (7 males, 20 females; mean age, 7.3 +/- 1.0; mean BMI z-score, 2.2 +/- 0.4). Fasting glucose (G(0)), insulin (I(0)), PI(0), androgen levels, insulin-like growth factor 1, insulin-like growth factor binding protein 1, and lipid levels were obtained. An oral glucose tolerance test was performed. EIR was calculated as (I(30) - I(0))/(G(30) - G(0)). Between-group differences were assessed by 2-way analysis of variance, with interactions and associations explored with correlation/regression.

Results: EIR was greater in the obese subjects with and without premature adrenarche. Combined analysis of the independent variables obesity and premature adrenarche showed that the obese premature adrenarche group had the highest EIR. The obese subjects with premature adrenarche had greater fasting PI levels than their lean counterparts. The differences in fasting PI/I ratio among the groups were not statistically significant.

Conclusions: Using EIR and PI as markers to assess the risk of insulin resistance and impaired insulin secretion indicates that obese children with premature adrenarche may be at greater risk for the development of prediabetes and type 2 diabetes mellitus compared with their lean counterparts.