Objective: We assessed whether beta-cell function progressively decreases over time with greater type 1 diabetes mellitus (T1DM) duration using a mixed-meal tolerance test (MMTT). We also assessed simpler and more practical surrogate parameters for clinical use.
Methods: We studied 57 children and adolescents with T1DM in Hangzhou (China), mean age at diagnosis was 8.3 years (range 2.3 to 15.3 years), with an average diabetes duration of 2.5 years (range 2 weeks to 8 years). A 120-minute MMTT was performed with plasma C-peptide measurements taken every 30 minutes. Urine C-peptide and creatinine levels were measured at 0 and 120 minutes. Severe insulin deficiency(SID) was defined as a C-peptide peak from the MMTT <0.2 nmol/l.
Results: Every one-year increase in diabetes duration was associated with a 37% decrease in C-peptide AUC (P<0.001). The rate of SID steadily increased over time, being particularly marked after two years when the rate increased from 13% to 67%. In addition, every one-year decrease in age at T1DM diagnosis was associated with a 20% decrease in C-peptide AUC (P=0.005). There was a consequent decline in the rate of SID with increasing age at diabetes diagnosis, with a 86% prevalence among children under 5 years of age compared to virtually no cases among children aged 11 years or older. Fasting C-peptide levels were perfectly corrected with both C-peptide peak and AUC.The C-peptide peaks at any time point had 100% sensitivity and thus were able to detect all cases of SID (n=25). However, the peak at 0120 min was the only one with 100% specificity, with no false positives. Fasting C-peptide was somewhat accurate to detect cases of SID, missing just one case (sensitivity 96%) and with no false positives (100% specificity). Urine C-peptide/creatinine at 120 minutes had 100% sensitivity, but poor specificity at 63% with 11 false positives (out of 30 negatives). Urine C-peptide peak had nearly perfect sensitivity at 96%, and its specificity was considerable better than that of the ratio at 87%.
Conclusions: There seems to be a steady decrease in beta-cell function with increasing duration of T1DM. In addition, children diagnosed at a younger age tend to have a much more marked loss in beta-cell function. Importantly, we showed that surrogate makers can be used in a routine clinical setting to detect SID in Chinese children and adolescents, particularly fasting C-peptide levels and a 120-minute urine C-peptide peak.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology