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Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes

Per Lundkvist1, Annika Grönberg2, Per-Ola Carlsson3,4

  • 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden per.lundkvist@medsci.uu.se.

BMJ Open Diabetes Research & Care
|February 27, 2024
PubMed

Insights

Biomarkers do not reliably predict type 1 diabetes progression in children. While some markers like CAR showed changes over time in rapid progressors, overall, predicting disease speed remains challenging.

Area of Science:

  • Endocrinology and Metabolism
  • Immunology
  • Pediatrics

Background:

  • Type 1 diabetes progression to insulin deficiency varies significantly.
  • Predicting disease progression is crucial for intervention trials in pediatric type 1 diabetes.
  • Identifying biomarkers for rapid versus slow progression is needed.

Purpose of the Study:

  • To identify biomarkers that predict rapid or slow disease progression in children with new-onset type 1 diabetes.
  • To compare biomarker profiles between rapid and slow progressors and healthy controls.

Main Methods:

  • Retrospective longitudinal cohort study of 46 children with type 1 diabetes.
  • Grouped children into rapid (<30 months) and slow progressors based on C-peptide levels.
  • Assessed multiple biomarkers using proximity extension assay (PEA) at baseline and follow-up, including a healthy control group (N=45).

Main Results:

  • Rapid progressors had lower C-peptide and higher autoantibodies at baseline.
  • Three baseline biomarkers (carbonic anhydrase 9, corticosteroid 11-beta-dehydrogenase isozyme 1, tumor necrosis factor receptor superfamily member 21) were higher in the rapid group.
  • A coxsackievirus B-adenovirus receptor (CAR) increased over time specifically in rapid progressors; 81 proteins differed between type 1 diabetes and controls, but PCA could not distinguish progression groups.

Conclusions:

  • Proximity extension assay (PEA) analysis of multiple biomarkers could not distinguish the rate of type 1 diabetes progression in children.
  • The coxsackievirus B-adenovirus receptor (CAR) showed a significant time-dependent increase in rapid progressors.
  • Specific biomarkers may still offer insights into C-peptide decline and type 1 diabetes pathogenesis, despite limitations in predicting progression speed.
Abstract

Keywords:
BiomarkersC-PeptideChildrenDiabetes Mellitus, Type 1

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