Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus
Aims/hypothesisWe aimed to identify circulating microRNA (miRNA) that predicts clinical progression in a cohort of 123 children with new onset type 1 diabetes mellitus.MethodsPlasma 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.ResultsIn 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/interpretationThe 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.
Diabetologia