Endocrine Abstracts

Context: Since the exact cause of type 1 diabetes mellitus (T1DM) remains unclear, the detection of novel biomarkers is necessary to complement the information obtained from the presence of autoantibodies together with genetic and environmental risk factors. MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression. Changes in their expression were described in several pathological conditions, including autoimmune diseases. Circulating miRNAs are attractive biomarker candidates as they can be easily collected, are stable under different storage conditions and can be measured using specific assays.

Objective: To investigate a miRNA expression profile in plasma from patients with T1DM and nondiabetic controls and suggest their targets using bioinformatics analysis.

Design: Expressions of 48 miRNAs were investigated in the plasma from 33 T1DM patients and 26 age-and-gender-matched controls using Stem-loop RT-PreAmp Real-time PCR and TaqMan Low Density Array cards (Thermo Scientific Inc). Five dysregulated miRNAs were chosen for validation using RT-qPCR in an independent sample (27 T1DM patients and 14 age-and-gender-matched controls).

Results: Nine miRNAs were differentially expressed between controls and T1DM patients with <5 years of diagnosis: 1 miRNA was downregulated (has-miR-146a-5p) while 8 miRNAs were upregulated (hsa-miR-101-3p, hsa-miR-103a-3p, hsa-miR-1275, hsa-miR-146a-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-200a-3p, hsa-miR-210-5p and hsa-miR-21-5p) in patients with <5 years of T1DM diagnosis compared to controls. In contrast, no differences were detected between controls and T1DM patients with >5 years of diagnosis. Bioinformatics analysis evidenced that hsa-miR-103a-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-200a-3p and hsa-miR-210-3p participate in pathways associated with T1DM pathogenesis, such as apoptosis, insulin and immune system.

Conclusions: Our data demonstrate that 9 miRNAs are differentially expressed in T1DM patients in the first years of the diagnosis. Our study also provided novel information about biological pathways implicated in T1DM. Ongoing studies will further explore the role of these miRNAs as possible novel biomarkers for T1DM prediction.