The addition of timing measures of C-peptide responsiveness may partly explain the glycated hemoglobin (HbA1c) level variation at diagnosis of type 1 diabetes (T1D), according to study results published in Pediatric Diabetes.

Previous studies have reported C-peptide responsiveness changes during the progression to T1D, but there are no data regarding the timing of C-peptide responses at diagnosis and the association with glucose levels. The goal of this trial was to study whether timing of C-peptide responsiveness during oral glucose tolerance test (OGTT) might explain variance in HbA1c levels at diagnosis of T1D.

The investigators used data from the Diabetes Prevention Trial-Type 1, which provides the opportunity to assess C-peptide responsiveness at diagnosis of T1D because patients were diagnosed by OGTT before administration of exogenous insulin, which may interfere with C-peptide responsiveness.

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The trial enrolled 85 patients age <18 years at diagnosis (mean age, 11.2 years; 51% boys) with complete OGTT data and HbA1c measurement at diagnosis. Peak C-peptide, area under the curve C-peptide, and measures of relative timing were recorded, including early C-peptide response, late C-peptide response, the 120-minute/30-minute C-peptide ratio, and time to peak C-peptide.

There was an inverse correlation between HbA1c with measures of overall C-peptide responsiveness: area under the curve C-peptide (r =-0.34; P <.001) and peak C-peptide (r =-0.37; P <.001). The inverse correlation was consistent with both early and late C-peptide responses (r =-0.34 and -0.38, respectively; P <.001 for both) and the 120-minute/30-minute C-peptide ratio (r =-0.40; P <.001).

In 27 patients with a peak C-peptide at ≤60 minutes, HbA1c levels were higher compared with 58 participants with a peak C-peptide at >60 minutes (6.5% ± 0.9% vs 5.9% ± 0.6%, respectively; P =.003).

Multivariable regression models showed that the addition of measures of timing of C-peptide responsiveness assisted in explaining HbA1c variance.

Similar to HbA1c, there was also inverse correlation between 2-hour glucose levels after OGTT with early and late C-peptide responses (r =-0.43 and -0.46, respectively; P <.001).

The researchers indicated that the study had several limitation, including the use of HbA1c measurements in analysis, which are more indicative of blood glucose levels over 2 to 3 months and might not reflect the actual association between glucose levels and C-peptide at diagnosis.

“The consideration of the timing of insulin secretion following a glucose challenge would allow for a better characterization of beta-cell dynamic function at the diagnosis of type 1 diabetes,” concluded the researchers.


Ismail HM, Evans-Molina C, DiMgelio LA, et al. Association of HbA1c with the timing of C-peptide responses during the oral glucose tolerance test at the diagnosis of type 1 diabetes [published online March 20, 2019]. Pediatr Diabetes. doi:10.1111/pedi.12845

This article originally appeared on Endocrinology Advisor