Precision Prediction & Precision Medicine


Charlotte Vollenbrock, Dick Mul, Pim Dekker, Erwin Birnie, Martine de Vries, Lianne Boesten, Joost Groen, Nel Geelhoed-Duijvestijn, Henk-Jan Aanstoot, Bruce Wolffenbuttel

Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus. Diabet Med . 2023 Feb;40(2):e15012.

In 2016 the ‘Biomarkers of heterogeneity in type 1 diabetes’ project was set up. In this project we are searching for biomarkers in people with established (>5 years) type 1 diabetes. The goal of this study is to investigate the associations between clinical, (auto)immune, metabolic, inflammatory and other parameters, and (potential) biomarkers. Blood and urine samples were collected annually (over 2 years) in standardized conditions and biobanked. In addition, a subgroup of participants underwent mixed meal-tests.


One of the research questions was how many people with type 1 diabetes show remaining insulin production as measured by C-peptide levels (using high-sensitive C-peptide assays) and if there are associations between remaining C-peptide production and clinical parameters. Earlier we already reported that residual C-peptide production is associated with a lower risk of both impaired awareness of hypoglycemia (IAH) and severe hypoglycemia (click here).


In this paper we aimed to evaluate the stability of C-peptide levels in people with type 1 diabetes over time (n=535). We also wanted to compare fasting C-peptide and C-peptide response after mixed-meal tolerance test (MMTT) after 90 minutes or 120 minutes with the C-peptide area under the curve (AUC) of the complete MMTT-curve (i.e. 0, 30, 60, 90 and 120 minutes) in long-standing type 1 diabetes, to see if the MMTT-procedure for assessment of detectable remaining C-peptide production could be simplified (n=168).

Key findings:

  • 25% of participants had detectable fasting serum C-peptide levels
  • Fasting C-peptide levels were significantly lower after 1 year
  • Participants with higher fasting C-peptide:
    • had higher age at diagnosis and shorter disease duration
    • were less frequently insulin pump users
  • 65% of participants had both non-detectable fasting and post-MMTT serum C-peptide concentrations
  • 90-minutes and 120-minutes timepoints showed good concordance with the MMTT total AUC


Concluding, the authors state


"Measuring C-peptide after MMTT identified an additional 10% of individuals with detectable C-peptide compared with measuring C-peptide in the fasting state, while 90-minutes and 120-minutes timepoints after MMTT showed good concordance with the MMTT total AUC. From a practical point of view, we propose to uniformly measure serum C-peptide concentration 90 minutes after mixed-meal ingestion for the estimation of residual insulin secretion in individuals with a longer diabetes duration" -

Please click here for the Pubmed link.


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