Circular RNAs in diabetes mellitus and its complications: a systematic review and in silico analyses

Circular RNAs (circRNAs) have garnered attention as potential biomarkers for diabetes mellitus (DM) and its complications due to their stability and presence in various tissues and plasma. The objective of this study was to perform a systematic review of the available literature to better understand the involvement of circRNAs in DM and its chronic complications.

PubMed and Embase repositories were searched to identify all studies that evaluated the expression of one or more circRNAs in samples from individuals with DM and without DM. Studies comparing circRNA expression between DM patients with or without chronic complications were also included.

In total, 2990 articles were found in the databases and, after excluding articles that did not meet the eligibility criteria, 130 articles were included in this systematic review. In these 130 studies, we identified over 3000 circRNAs differentially expressed between cases and controls. Among these, eight circRNAs were reported as altered in samples from three or more studies, which were selected for additional evaluations. Five of them were consistently dysregulated between DM patients and controls. The circRNAs hsa_circ_0000324 and hsa_circ_0060450 were increased, while the hsa_cic_0080325 was decreased in type 1 DM patients vs. controls. Moreover, hsa_circ_0054633 was increased in type 2 DM patients vs. controls, and hsa_circ_0003218 was decreased in gestational DM patients vs. controls. Regarding chronic DM complications, three circRNAs were identified as dysregulated: hsa_circ_0037128 and hsa_circ_0003928 in diabetic kidney disease and hsa_circ_0006057 in diabetic retinopathy.

Eight circRNAs are dysregulated in DM and its chronic complications.