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

Pediatr Diabetes. 2011 May;12(3 Pt 2):242-9. doi: 10.1111/j.1399-5448.2010.00734.x. Epub 2011 Mar 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Body Weight
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Female
  • Germany / epidemiology
  • Glucose Tolerance Test
  • Humans
  • Infant
  • Insulin Resistance*
  • Male
  • Metabolic Syndrome / blood
  • Obesity / blood*
  • Obesity / ethnology
  • Proinsulin / blood*
  • Puberty
  • Sex Characteristics
  • Young Adult

Substances

  • Proinsulin