A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes
Guido Sebastiani, Giuseppina Emanuela Grieco, Marco Bruttini, Stefano Auddino, Alessia Mori, Mattia Toniolli, Daniela Fignani, Giada Licata, Elena Aiello, Laura Nigi, Caterina Formichi, Juan Fernández‐Tajes, Alberto Pugliese, Carmella Evans‐Molina, Lut Overbergh, Timothy Tree, Mark Peakman, Chantal Mathieu, Francesco Dotta
Abstract
Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.