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

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.