Mapping Circulating Microrna Signatures in Type 1 Diabetic Microvascular Disease: A Systematic Review and Bayesian Multilevel Meta-Analysis With Bioinformatic Integration of Molecular Dysregulation Publisher Pubmed



Khadivi Y ; Tavallaeinejad P ; Hashemipour M ; Khachikian A ; Hovsepian S
Source: Metabolism: Clinical and Experimental Published:2026

Abstract

Background To systematically evaluate microRNAs (miRNAs) associated with microvascular complications of type 1 diabetes mellitus (T1D), quantify differential expression using complementary frequentist and Bayesian meta-analytic frameworks, and contextualize dysregulated signals through integrative multi-database pathway analysis. Methods A systematic search of Medline, Embase, Scopus, and Web of Science was conducted through February 2025 to identify observational studies reporting miRNA expression in diabetic nephropathy (DN) or diabetic retinopathy (DR). Effect sizes (Hedges' g) were pooled using random-effects models and Bayesian hierarchical meta-analysis to account for within-study dependence. Experimentally validated and predicted targets were retrieved via multiMiR and mapped to Gene Ontology, KEGG, and Reactome pathways to evaluate biological convergence. Results Nine studies comprising 34 contrasts and 19 unique miRNAs met inclusion criteria. miR-29a-3p (g = −0.99; 95% CI −1.33 to −0.65; I2 = 0.00) and miR-204-5p (g = −0.88; 95% CI −1.06 to −0.70; I2 = 0.00) were consistently downregulated in DN. Bayesian models corroborated frequentist estimates, demonstrated robust convergence, and showed minimal sensitivity to prior specification. No universal circulating miRNA signature emerged across complications, reflecting substantial biological and methodological heterogeneity. Enrichment analyses of validated targets indicated convergence on pathways related to autophagy, Wnt signaling, fibrosis, and apoptosis. Conclusion Current evidence does not support a unified circulating miRNA signature for T1D microvascular complications. However, reproducible downregulation of miR-29a-3p and miR-204-5p highlights candidate signals warranting validation in adequately powered longitudinal and diagnostic-accuracy studies. By integrating quantitative synthesis with pathway-level interpretation, this study clarifies the present evidentiary landscape and provides a framework to guide future translational research in T1D microangiopathy. Copyright © 2026. Published by Elsevier Inc.