Proinsulin and the proinsulin/insulin ratio in overweight and obese children and adolescents: relation to clinical parameters, insulin resistance, and impaired glucose regulation.

BACKGROUND: In adults with impaired glucose regulation (IGR) or type 2 diabetes mellitus (T2DM), proinsulin (PI) and its ratio to insulin (ins; PI/I ratio) are frequently elevated.
OBJECTIVE: Here we assessed the relationship among fasting PI, clinical parameters, and carbohydrate metabolism, a potential difference of the PI/I ratio between overweight and obese youth with or without IGR in an oral glucose tolerance test (OGTT) and the predictive power of PI levels for IGR. DESIGN AND PATIENTS: In a cross-sectional study, data of n = 259 children and adolescents attending our obesity clinic were studied.
METHODS: Fasting PI levels were determined in all patients and matched to the standard assessment of obesity. In n = 154 subjects at risk for T2DM, an OGTT was performed sampling for glucose, ins, and PI. MAIN OUTCOME MEASURES: ins, glucose, PI, PI/I ratio, insulin resistance [homeostasis model assessment of insulin resistance index (HOMA-IR)].
RESULTS: Puberty (by Tanner) and relative body weight [body mass index (BMI)-standard deviation of BMI (SDS)] showed a linear relationship to fasting PI levels (p < 0.001 for Tanner I vs. II-V; p = 0.04 and p = 0.026 for BMI-SDS < 2 vs. 2-2.5 and 2-2.5 vs. > 2.5, respectively). Subjects with ins resistance (HOMA-IR > 95th percentile, n = 140) had higher fasting PI levels than those without (p < 0.001), with no significant difference in fasting PI/I ratio (p > 0.05). As compared to subjects with normal glucose regulation, subjects with IGR (n = 35) had higher fasting PI (p = 0.001) and an increased PI/I ratio, both during fasting and at 30 min during OGTT (p = 0.049 and p = 0.014, respectively).
CONCLUSIONS: Children and adolescents with IGR have disproportionately elevated PI levels, both during fasting and after acute glucose stimulation indicating β-cell dysfunction.