Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes

World J Pediatr. 2021 Feb;17(1):99-105. doi: 10.1007/s12519-020-00382-0. Epub 2021 Jan 7.

Abstract

Background: No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population.

Methods: Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes.

Results: Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged ≥ 11 years.

Conclusions: Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

Keywords: Endogenous insulin secretion; Mixed-meal tolerance test (MMTT); Type 1 diabetes mellitus.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Insulin Secretion*
  • Male

Substances

  • Biomarkers