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

Willemsen, R. H.; Burling, K.; Barker, P.; Ackland, F.; Dias, R. P.; Edge, J.; Smith, A.; Todd, J.; Lopez, B.; Mander, A. P.; Guy, C.; Dunger, D. B.

doi:10.1101/286237

bioRxiv · 10.1101/286237

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

Willemsen, R. H.·Burling, K.·Barker, P.·Ackland, F.·Dias, R. P.·Edge, J.·Smith, A.·Todd, J.·Lopez, B.·Mander, A. P.·Guy, C.·Dunger, D. B.

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Abstract

ObjectiveTo evaluate a novel approach to measure {beta}-cell function by frequent testing of C-peptide concentrations in dried blood spots (DBS)\n\nPatientsThirty-two children, aged 7-17 years, recently diagnosed with type 1 diabetes.\n\nDesignMixed-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.\n\nResultsDBS and plasma C-peptide levels (n=115) correlated strongly (r=0{middle dot}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{middle dot}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.\n\nConclusionOur approach permitted frequent assessment of C-peptide, making it feasible to monitor {beta}-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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Willemsen, R. H., Burling, K., Barker, P., Ackland, F., Dias, R. P., Edge, J., Smith, A., Todd, J., Lopez, B., Mander, A. P., Guy, C., Dunger, D. B.. 2018-03-21. Frequent Monitoring of C-peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home. https://doi.org/10.1101/286237

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