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

Nasim Samandari1, Aashiq H Mirza1,2, Lotte B Nielsen1

  • 1Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Paediatrics, Herlev and Gentofte Hospitals, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.

Diabetologia
|November 21, 2016
PubMed

Insights

Circulating microRNAs (miRNAs) can predict type 1 diabetes progression. Specifically, hsa-miR-197-3p at 3 months post-diagnosis is a strong indicator of beta cell function one year later in children.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells.
  • Predicting clinical progression and residual beta cell function in new-onset T1DM is crucial for personalized treatment strategies.
  • MicroRNAs (miRNAs) are small non-coding RNAs that play regulatory roles in various biological processes, including beta cell function and immune responses.

Purpose of the Study:

  • To identify circulating miRNAs that predict clinical progression in children with new-onset type 1 diabetes mellitus.
  • To evaluate the predictive value of specific miRNAs for residual beta cell function and glycemic control.
  • To validate identified miRNA biomarkers in a larger cohort.

Main Methods:

  • Prospective collection of plasma samples from 123 children with new-onset T1DM at multiple time points post-diagnosis.
  • miRNA profiling of plasma samples from a subset of 40 children.
  • Measurement of meal-stimulated C-peptide and HbA1c levels, with calculation of insulin-dose adjusted HbA1c (IDAA1c).
  • Validation of candidate miRNAs in the remaining cohort (n=83) using multiple linear regression analysis.

Main Results:

  • Six miRNAs (hsa-miR-24-3p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-197-3p, hsa-miR-301a-3p, hsa-miR-375) at 3 months correlated with residual beta cell function at 6-12 months.
  • hsa-miR-197-3p at 3 months significantly predicted stimulated C-peptide at 12 months (p=0.034).
  • hsa-miR-24-3p and hsa-miR-146a-5p at 3 months predicted lower IDAA1c at 12 months (p<0.014 and p<0.022, respectively).
  • The predictive value of hsa-miR-197-3p was confirmed in the validation cohort (p=0.018).

Conclusions:

  • The miRNA hsa-miR-197-3p, detected 3 months after diagnosis, is a strong predictor of residual beta cell function one year later in children with T1DM.
  • Circulating miRNAs, particularly hsa-miR-197-3p, hold potential as non-invasive biomarkers for predicting T1DM progression and guiding therapeutic interventions.
  • Further research into the target genes of these miRNAs may elucidate pathways involved in T1DM pathogenesis, including those related to the gonadotropin-releasing hormone receptor and angiogenesis.
Abstract

Keywords:
BiomarkersChildrenResidual beta cell functionmiRNA

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