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

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

Author information

1
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev and Gentofte Hospitals, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.
2
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark.
3
Department of Statistics, University of Southern Denmark, Odense, Denmark.
4
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev and Gentofte Hospitals, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark. flemming.pociot.01@regionh.dk.
6
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark. flemming.pociot.01@regionh.dk.
7
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. flemming.pociot.01@regionh.dk.

Abstract

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

PMID:
27866223
DOI:
10.1007/s00125-016-4156-4
[Indexed for MEDLINE]

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