ESPE Abstracts

Background: Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune destruction of pancreatic beta-cells. Dysregulated miRNA levels have been described in T1D patients, though results are inconclusive.

Objective and Hypotheses: The aim of this study was to assess the circulating profile of different miRNAs in children at diagnosis of T1D.

Method: 27 children with T1D onset (16M/11F) and 26 controls (16M/10F) underwent anthropometric, biochemical and metabolic evaluation. Insulin antibodies (IAA), glutamic acid decarboxylase antibodies (GAD), and islet tyrosine phosphatase-2 antibodies (IA2) were assessed in T1D patients. Serum levels of several miRNAs (miR-21, miR-181, miR-25, miR-126, miR-148, miR-486, miR-345, miR-222, miR-140, miR-454, miR-125, miR-636, miR-500, miR-375 and miR-383) were analyzed by qPCR.

Results: Age was not different between T1D and control subjects (6.9 ± 3.9 yrs vs 6 yrs ± 2.8 yrs, P=0.313) as well as weight (-0.43 ± 1.06 SDS vs –0.16 ± 1.46 SDS, P=0.458) and height (0.22 ± 1.39 SDS vs 0.76 ± 3.8 SDS, P=0.513). MiRNA serum levels were similar between females and males except for miR-500, significantly higher in males than females (P=0.03). MiR-126 was lower in T1D patients (P=0.016) whereas miR-486 and miR140 were higher in T1D subjects compared to controls (P<0.05). In T1D male subjects miR-21 serum levels were lower compared to controls (P=0.003). In T1D subjects, miR-21 correlated with IA2 (r=0.468, P=0.032) and GAD antibodies (r=0.423, P=0.05). miR-140 correlated with C-peptide levels (r=0.991, P=0.009), HDL-cholesterol levels (r=0.958, P=0.042) and Triglycerides/HDL ratio (r=0.993, P=0.007).

Conclusions: T1D subjects have a different circulating miRNA profile compared to age, gender and weight matched controls. miR-140 is upregulated at T1D onset and correlates with residual beta cell function. The observed relationships of miRNAs with islet cell autoantibodies and metabolic parameters warrant further investigations to evaluate their possible use either as predictors or as markers of disease progression.