Background: The majority of drug developments in type 1 diabetes (T1D) are aimed at preventing decline of beta cell function (BCF), as this has been associated with better glycaemic control and fewer long-term complications. Traditionally, BCF is evaluated by the C-peptide response to the labour-intensive mixed-meal-tolerance-test (MMTT), but theres a need for a more practical alternative. We developed a new method to measure C-peptide in dried blood spots (DBS).
Objective: To explore the use of a novel method to detect residual BCF in children recently diagnosed with T1D.
Method: 26 T1D-subjects aged 6.916.5 years (10M;16F) had a MMTT within 6 months of diagnosis and 12 months after diagnosis with paired sampling of venous and DBS C-peptide at 0 and 90 minutes, and a urine sample for C-peptide/creatinine-ratio. In between MMTTs, weekly DBS C-peptide measurements before and after a standard breakfast were collected at home.
Results: DBS and plasma C-peptide levels correlated well (n=85 paired measurements; r=0.95; P<0.001). All but 2 subjects had detectable fasting and postprandial DBS C-peptide throughout the study. Median fasting DBS C-peptide levels (range) at 6, 9 and 12 mo from diagnosis were 308 (<50834), 210(<501299) and 272(<50967) pmol/l, respectively. In multiple regression models with time and glucose as covariates of 21 cases with a median (range) of 24(829) home DBS measurements, fasting and post-prandial DBS C-peptide were negatively affected by time in 67 and 71%, and positively affected by glucose levels in 67 and 43%, respectively. A significant interaction between fasting or post-prandial glucose and time was identified in 19 and 5% of cases, respectively, indicating that glucose responsiveness decreased over time. The decline in fasting DBS C-peptide correlated well with that identified by the MMTT (r=0.80; P=0.002) and the urine C-peptide/creatinine ratio (r=0.77; P=0.004).
Conclusion: DBS C-peptide measurement can be a useful tool in evaluating BCF in T1D intervention studies.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology