Precision Prediction & Precision Medicine


Martine J Wellens, Charlotte E Vollenbrock, Pim Dekker, Lianne S M Boesten, Petronella H Geelhoed-Duijvestijn, Martine M C de Vries-Velraeds, Giesje Nefs, Bruce H R Wolffenbuttel , Henk-Jan Aanstoot, Peter R van Dijk

Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes. BMJ Open Diabetes Res Care . 2021 Sep;9(1):e002288.

We are happy to report publication of the first data of the ‘Biomarkers of heterogeneity in type 1 diabetes’ study.


Impaired awareness of hypoglycemia (IAH), the inability to detect the onset of hypoglycemia, is a serious consequence of long-duration diabetes mellitus. About 20% – 40% of people with type 1 diabetes develop IAH. With increasing age, symptom intensity decreases and IAH prevalence increases. It has already been shown that IAH is associated with higher risk of asymptomatic and severe hypoglycemia and a lower quality of life. About 30% -80% of people with longstanding type 1 diabetes show (some) residual C-peptide production, which has been linked to a lower risk of severe hypoglycemia. The authors hypothesized that the presence of residual C-peptide production may be associated with the absence of IAH. Associations with other clinical variables we also assessed.


A cross-sectional analysis of data collected between January 2016 and May 2019 from the ‘Biomarkers of heterogeneity in type 1 diabetes’ ( Identifier: NCT04977635) was performed.


Key findings:

  • Independent risk factors for IAH were:
    • Higher BMI
    • Microvascular complications
    • Higher age at type 1 diabetes onset
  • IAH and severe hypoglycemia in the preceding year were strongly associated
  • Residual C-peptide production was associated with a lower risk of both IAH and severe hypoglycemia.


Please find full text pdf here.

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