Circulating plasma/serum microRNAs in type 2 diabetes mellitus and Its complications: A systematic review and meta-analysis of diagnostic test accuracy

Document Type

Review Article

Department

Medical College Pakistan; Biological and Biomedical Sciences

Abstract

Purpose: Circulating microRNAs (miRNAs) have emerged as potential non-invasive biomarkers for type 2 diabetes mellitus (T2DM), but reported diagnostic performance varies across studies. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs for identifying T2DM and its complications.
Methods: Three databases (PubMed, Scopus, and the Cochrane Library) were searched from inception to December 2024. Studies assessing circulating miRNA expression in adults with T2DM compared with healthy or pre-diabetic controls were included. The meta-analysis only included studies reporting AUC values. Diagnostic accuracy data were synthesized using a bivariate random-effects model. Risk of bias was assessed using QUADAS-2.
Results: Thirty studies comprising 3,090 participants were included in the meta-analysis. The pooled sensitivity and specificity of circulating miRNAs for diagnosing T2DM were 0.88 (95% CI 0.84–0.91) and 0.88 (95% CI 0.84–0.92), respectively, with an area under the summary ROC curve of 0.94. The most frequently reported and diagnostically accurate miRNAs across studies were miR-21, miR-375, and miR-32-5p. Diagnostic performance was similar in studies evaluating uncomplicated T2DM and those including diabetic complications. Sensitivity analyses confirmed the robustness of these findings. All studies demonstrated high risk of bias in patient selection, largely due to case-control designs. Variation in comparator groups across studies may also influence the reported diagnostic performance.
Conclusion: Circulating miRNAs, particularly miR-21, miR-32-5p, and miR-375, emerged as candidate biomarkers with potential diagnostic value for T2DM and its complications, consistent with their roles in insulin signaling. Methodological heterogeneity and high risk of bias across studies limit confidence, and pooled estimates may overstate real-world performance. Prospective, standardized, and clinically representative studies are needed to validate their utility before clinical implementation.

Publication (Name of Journal)

Endocrine

DOI

10.1007/s12020-026-04641-4

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