Associations of HbA1c with the timing of C-peptide responses during the oral glucose tolerance test at the diagnosis of type 1 diabetes

Pediatr Diabetes. 2019 Jun;20(4):408-413. doi: 10.1111/pedi.12845. Epub 2019 Apr 15.

Abstract

Background: In new onset type 1 diabetes (T1D), overall C-peptide measures such as area under the curve (AUC) C-peptide and peak C-peptide are useful for estimating the extent of β-cell dysfunction, and for assessing responses to intervention therapy. However, measures of the timing of C-peptide responsiveness could have additional value.

Objectives: We assessed the contribution of the timing of C-peptide responsiveness during oral glucose tolerance tests (OGTTs) to hemoglobin A1c (HbA1c) variation at T1D diagnosis.

Methods: We analyzed data from 85 individuals <18 years with OGTTs and HbA1c measurements at diagnosis. Overall [AUC and peak C-peptide] and timing measures [30-0 minute C-peptide (early); 60 to 120 minute C-peptide sum-30 minutes (late); 120/30 C-peptide; time to peak C-peptide] were utilized.

Results: At diagnosis, the mean (±SD) age was 11.2 ± 3.3 years, body mass index (BMI)-z was 0.4 ± 1.1, 51.0% were male. The average HbA1c was 43.54 ± 8.46 mmol/mol (6.1 ± 0.8%). HbA1c correlated inversely with the AUC C-peptide (P < 0.001), peak C-peptide (P < 0.001), early and late C-peptide responses (P < 0.001 each), and 120/30 C-peptide (P < 0.001). Those with a peak C-peptide occurring at ≤60 minutes had higher HbA1c values than those with peaks later (P = 0.003). HbA1c variance was better explained with timing measures added to regression models (R2 = 11.6% with AUC C-peptide alone; R2 = 20.0% with 120/30 C-peptide added; R2 = 13.7% with peak C-peptide alone, R2 = 20.4% with timing of the peak added). Similar associations were seen between the 2-hour glucose and the C-peptide measures.

Conclusions: These findings show that the addition of timing measures of C-peptide responsiveness better explains HbA1c variation at diagnosis than standard measures alone.

Keywords: C-peptide; HbA1c; OGTT; glycemia; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / genetics
  • Blood Glucose / metabolism
  • C-Peptide / analysis
  • C-Peptide / metabolism*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Genetic Association Studies
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Time Factors
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A