Circulating miRNA-375 levels are increased in autoantibodies-positive first-degree relatives of type 1 diabetes patients

Growing evidence suggests that microRNAs (miRNAs) play a key role in beta-cell metabolism, proliferation and apoptosis, and in immune system functions, all processes involved in the pathogenesis of type 1 diabetes. In the context of diabetes, particular attention has been focused on miR-375, which has been studied most extensively as a putative biomarker of beta cell death. Although dysregulated miRNA profiles have been identified in type 1 diabetes patients, results are inconclusive. The aim of our study was to evaluate miR-375 levels in a very large and carefully selected cohort of 142 Sardinian subjects, which included 49 type 1 diabetes subjects, 46 autoantibodies (Aabs) positive first-degree relatives (FDR) of type 1 diabetes patients and 48 healthy controls. We observed that Aabs-positive FDR subjects showed significantly (p=1x10-6) increased levels of miR-375 compared to type 1 diabetes patients and healthy controls. Also, we observed that increased circulating miR-375 associated with later onset of diabetes, and a direct correlation between C-peptide levels and miR-375 levels, reflecting a longer β-cell residual function. However, ROC analysis to assess the possible predictive role of miR-375 levels on the diagnosis of type 1 diabetes in the FDR that were followed longitudinally did not show any predictive role (AUC 0.50). Hence, our results confirm the role of miR-375 in the autoimmune process of type 1 diabetes, but its utility as a single biomarker does not emerge as clinically applicable.