Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance.

Objectives: We compared the fasting serum proinsulin levels in lean, overweight, and obese prepubertal children with normal glucose tolerance (NGT). We also evaluated the relationship between fasting proinsulin level and indices of insulin resistance (IR).

Subjects And Methods: One hundred nine prepubertal children (mean age, 8.6 yr) with NGT were included. The indices of IR included the homeostasis model assessment of IR (HOMA-IR) and adiponectin level. We recorded the presence of one or more of the following metabolic derangements: triglycerides ≥ 150 mg/dL, HDL-cholesterol < 35 mg/dL, and hypertension.

Results: Fasting proinsulin levels significantly increased with body mass index (BMI) category from lean (n = 52, 7.22 ± 3.01 pmol/L) to overweight (n = 14, 12.31 ± 2.91 pmol/L) to obese (n = 43, 16.51 ± 7.27 pmol/L) (p < 0.001), after controlling for HOMA-IR. The ratio of the fasting levels of proinsulin to insulin did not differ significantly between the three groups. Both BMI z-score and HOMA-IR were significant independent factors related to the fasting proinsulin level (p < 0.001 for each). A significant inverse association was found between fasting proinsulin level and adiponectin level (r = -0.464, p < 0.001). Children with NGT who had at least one metabolic derangement had higher proinsulin levels than those without metabolic derangement.

Conclusions: Obesity itself or obesity-related IR may independently impose β-cell overload on prepubertal children with NGT, leading to hyperproinsulinemia without causing failure to convert proinsulin to insulin when some degree of IR and metabolic derangement appears.