Frequent Monitoring of C-peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home.

Willemsen, Ruben H 
Burling, Keith 
Barker, Peter 
Ackland, Fran 
Dias, Renuka P 

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Objective: To evaluate a novel approach to measure ß-cell function by frequent testing of C-peptide concentrations in 'dried blood spots' (DBS). Patients: Thirty-two children, aged 7-17 years, recently diagnosed with type 1 diabetes. Design: Mixed-meal-tolerance-test (MMTT) within 6 and again 12 months after diagnosis with paired venous and DBS C-peptide sampling at 0 and 90 minutes. Weekly DBS C-peptide before and after standardized breakfasts collected at home. Results: DBS and plasma C-peptide levels (n=115) correlated strongly (r=0·91; p<0.001). The Bland-Altman plot indicated good agreement. The median number of home-collected DBS cards per participant was 24 over a median of 6.9 months. Repeated DBS C-peptide levels varied considerably within and between subjects. Adjustment for corresponding home glucose measurements reduced the variance permitting accurate description of changes over time. The correlation of the C-peptide slope over time assessed by repeated home DBS versus area under the curve during the two MMTTs was r=0·73; p<0.001. Mixed models showed that a 1-month increase of diabetes duration was associated with 17 pmol/l decline in fasting DBS C-peptide, whereas increases of 1 mmol/l in glucose, 1 year older age-at-diagnosis and 100 pmol/l higher baseline plasma C-peptide were associated with 18, 17 and 61 pmol/l higher fasting DBS C-peptide levels, respectively. In addition, glucose responsiveness decreased with longer diabetes duration. Conclusion: Our approach permitted frequent assessment of C-peptide, making it feasible to monitor ß-cell function at home. Evaluation of changes in the slope of C-peptide using this method may permit short-term evaluation of promising interventions.

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Adolescent, Area Under Curve, Blood Glucose, Blood Glucose Self-Monitoring, C-Peptide, Child, Correlation of Data, Diabetes Mellitus, Type 1, Dried Blood Spot Testing, Fasting, Feasibility Studies, Female, Humans, Male, Time Factors
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Journal of Clinical Endocrinology and Metabolism
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Oxford University Press
European Commission Horizon 2020 (H2020) Societal Challenges (115797 INNODIA)
Helmsley Charitable Trust (via
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (091157/Z/10/B)
Novo Nordisk UK Research Foundation, NIHR Cambridge Biomedical Research Centre, JDRF (9-2011-253/5-SRA-2015-130-A-N), the Wellcome Trust (WT091157/107212 and WT083650/Z/07/Z) and the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115797 (INNODIA)). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation programme and “EFPIA”, ‘JDRF” and “The Leona M. and Harry B. Helmsley Charitable Trust”.