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.
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•Circulating miRNAs in T1DM individuals distinguish two groups: cluster A and cluster B•miR-409-3p, miR-127-3p, and miR-382-5p are increased in cluster B T1DM individuals•T1DM individuals in cluster B show an improved glycemic profile at follow-up•Blood immunomics show higher frequency of memory and exhausted T cells in cluster B
Sebastiani et al. found that circulating microRNAs, particularly those from the 14q32 locus, differentiate two distinct subgroups of individuals with type 1 diabetes mellitus, termed cluster A and cluster B. Cluster B, characterized by elevated expression of 14q32 miRNAs, exhibits better glycemic control and unique immunomics profiles, indicating potential implications for future interventional immunotherapies.