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

BackgroundIn 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 -cell dysfunction, and for assessing responses to intervention therapy. However, measures of the timing of C-peptide responsiveness could have additional value. ObjectivesWe assessed the contribution of the timing of C-peptide responsiveness during oral glucose tolerance tests (OGTTs) to hemoglobin A1c (HbA1c) variation at T1D diagnosis. MethodsWe analyzed data from 85 individuals <18years 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. ResultsAt diagnosis, the mean (SD) age was 11.2 +/- 3.3years, body mass index (BMI)-z was 0.4 +/- 1.1, 51.0% were male. The average HbA1c was 43.54 +/- 8.46mmol/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 60minutes had higher HbA1c values than those with peaks later (P=0.003). HbA1c variance was better explained with timing measures added to regression models (R-2=11.6% with AUC C-peptide alone; R-2=20.0% with 120/30 C-peptide added; R-2=13.7% with peak C-peptide alone, R-2=20.4% with timing of the peak added). Similar associations were seen between the 2-hour glucose and the C-peptide measures. ConclusionsThese findings show that the addition of timing measures of C-peptide responsiveness better explains HbA1c variation at diagnosis than standard measures alone.