Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes

Pediatr Diabetes. 2012 Feb;13(1):51-8. doi: 10.1111/j.1399-5448.2011.00812.x. Epub 2011 Nov 27.

Abstract

Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes.

Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C ≤ 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA).

Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p < 0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p < 0.0001) and IA (p = 0.0024, p = 0.0068, p < 0.0001) at 1, 6, and 12 months. Glucagon (p < 0.0001 and p < 0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002).

Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Age of Onset
  • Blood Glucose / analysis
  • C-Peptide / analysis
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Female
  • Follow-Up Studies
  • Glucagon / analysis
  • Glucagon / blood*
  • Glucagon-Like Peptide 1 / analysis
  • Glucagon-Like Peptide 1 / blood*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Proinsulin / analysis
  • Proinsulin / blood*
  • Remission, Spontaneous

Substances

  • Blood Glucose
  • C-Peptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Proinsulin