Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus

Diabetologia. 2017 Feb;60(2):354-363. doi: 10.1007/s00125-016-4156-4. Epub 2016 Nov 19.


Aims/hypothesis: We aimed to identify circulating microRNA (miRNA) that predicts clinical progression in a cohort of 123 children with new-onset type 1 diabetes mellitus.

Methods: Plasma samples were prospectively obtained at 1, 3, 6, 12 and 60 months after diagnosis from a subset of 40 children from the Danish Remission Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C-peptide and HbA1c levels were measured and insulin-dose adjusted HbA1c (IDAA1c) calculated. miRNAs that at 3 months after diagnosis predicted residual beta cell function and glycaemic control in this subgroup were further validated in the remaining cohort (n = 83). Statistical analysis of miRNA prediction for disease progression was performed by multiple linear regression analysis adjusted for age and sex.

Results: In the discovery analysis, six miRNAs (hsa-miR-24-3p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-197-3p, hsa-miR-301a-3p and hsa-miR-375) at 3 months correlated with residual beta cell function 6-12 months after diagnosis. Stimulated C-peptide at 12 months was predicted by hsa-miR-197-3p at 3 months (p = 0.034). A doubling of this miRNA level corresponded to a sixfold higher stimulated C-peptide level. In addition, a doubling of hsa-miR-24-3p and hsa-miR-146a-5p levels at 3 months corresponded to a 4.2% (p < 0.014) and 3.5% (p < 0.022) lower IDAA1c value at 12 months. Analysis of the remaining cohort confirmed the initial finding for hsa-miR-197-3p (p = 0.018). The target genes for the six miRNAs revealed significant enrichment for pathways related to gonadotropin-releasing hormone receptor and angiogenesis pathways.

Conclusions/interpretation: The miRNA hsa-miR-197-3p at 3 months was the strongest predictor of residual beta cell function 1 year after diagnosis in children with type 1 diabetes mellitus.

Keywords: Biomarkers; Children; Residual beta cell function; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Insulin-Secreting Cells / metabolism*
  • Male
  • MicroRNAs / genetics*
  • Prospective Studies


  • Blood Glucose
  • MIRN146 microRNA, human
  • MIRN194 microRNA, human
  • MIRN24 microRNA, human
  • MIRN375 microRNA, human
  • MicroRNAs