期刊
DIABETOLOGIA
卷 60, 期 2, 页码 354-363出版社
SPRINGER
DOI: 10.1007/s00125-016-4156-4
关键词
Biomarkers; Children; miRNA; Residual beta cell function
资金
- Capital Region of Denmark's Research Fund for Health Science
- European Foundation for the Study of Diabetes (EFSD-Novo Nordisk-JDRF)
- Beckett Foundation
- Savvaerksejer Jeppe Juhl og hustru Ovita Juhls mindelegat
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 HbA(1c) levels were measured and insulin-dose adjusted HbA(1c) (IDAA(1c)) 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 IDAA(1c) 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.
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