Plasma circulating microRNAs as potential biomarkers of disease progression in children with Type 1 Diabetes

Silvia Garavelli¹ Mario Galgani², Sara Bruzzaniti², Adriana Franzese³, Enza Mozzillo³, Giuseppe Matarese^2,4 and Paola de Candia¹,

¹Fondazione Multimedica Onlus, Milan, Italy. ²Istituto per l’Endocrinologia e l’Oncologia Sperimentale “G. Salvatore” Consiglio Nazionale delle Ricerche - Naples, Italy. ³Centro Regionale di Diabetologia Pediatrica, Università degli studi Federico II - Naples, Italy. ⁴Dipartimento di Biologia Molecolare e Biotecnologie Mediche, Università degli studi Federico II - Naples, Italy. 

Background and aims. Type 1 Diabetes (T1D) is an autoimmune disease characterized by lymphocyte-mediated destruction of the insulin producing b cells. The mechanism that triggers autoimmunity and how b cells fail to secrete insulin have not been yet completely understood and we need novel biomarkers able to predict the rate of disease progression. One highly suitable source of blood-associated biomarkers is represented by extracellular microRNAs (miRNAs) that, released by most cells in the body, reach the circulation, remain very stable, and may be used to assess cell activity at distance. The aim of our work was to test whether these T cell-derived circulating miRNAs may be used as biomarkers of T1D progression.

Methods. We have retrospectively screened plasma samples from T1D patients at disease onset (n=95) and healthy control subjects matched for age and sex (n=58). A subgroup of T1D patients (n=30) were also screened at two different time points after disease onset: T1 (1 year) and T2 (2 years). Plasma circulating miRNAs were profiled by RT-qPCR and miRNA quantities were analyzed.

Results. We have identified a group of disease-dependent differentially expressed miRNAs that are modulated in diabetic children compared to the healthy counterpart and/or upon disease progression. We also performed a correlation analysis to evaluate the relationship i) among the differentially expressed miRNAs and ii) between the miRNAs and available clinical data, including C-peptide, hemoglobin A1c and the blood circulating lymphocyte subset numbers. This analysis was able to highlight complex miRNA co-modulation patterns, and potentially important relations between miRNAs and the traditionally used disease markers at disease onset and 1 or 2 years after. In conclusion, the quantification of blood circulating miRNAs may lead to their validation as novel clinical parameters for T1D, directly connected to disease progression in vivo.