miRNAs as potential biomarkers for early detection of prediabetes among obesity: a systematic review

Abstract

Background: Prediabetes in individuals with obesity is a high-risk state for progression to type 2 diabetes mellitus (T2DM). Circulating microRNAs (miRNAs) have emerged as promising minimally invasive biomarkers for early detection. However, their diagnostic performance and consistency across studies remain unclear.

Objectives: To evaluate circulating miRNAs as potential biomarkers for prediabetes in obese populations.

Methods: A systematic search of PubMed, MEDLINE, Scopus, and EBSCOhost was conducted (September 2012-September 2025) without language restrictions. Eligible studies included observational, clinical, and translational research assessing circulating miRNAs in plasma, serum, whole blood, or exosomes using qRT-PCR, ddPCR, microarray, or next-generation sequencing. Two reviewers independently screened studies and extracted data using a piloted form. Extracted information was synthesized qualitatively; diagnostic performance measures and reported miRNAs were tabulated.

Results: Nine circulating microRNAs (miR-27, miR-30a, miR-34a, miR-93, miR-122, miR-126, miR-146a, miR-192, and miR-193b) were consistently dysregulated in obese individuals with prediabetes across thirteen included human studies. These miRNAs were linked to key pathogenic mechanisms including chronic inflammation, insulin resistance, β-cell dysfunction, and altered adipokine signaling. Notably, inflammation-associated miRNAs (miR-27, miR-34a, miR-146a) reflected the transition from metabolically healthy to unhealthy obesity, while β-cell-related miRNAs (miR-30a, miR-126) indicated early impairment of insulin secretion. Among detection platforms, qRT-PCR remained the most sensitive and specific method for miRNA quantification, whereas microarray and next-generation sequencing provided broader profiling capability but with higher cost and complexity.

Conclusions: Circulating miRNAs demonstrate promise as diagnostic biomarkers for prediabetes in obesity. However, these findings are limited by methodological variability. Thus, large-scale and standardized studies are required to validate their clinical utility.

Keywords: ROC; diagnostic accuracy; impaired fasting glucose; impaired glucose tolerance; metaanalysis.; miRNA; microRNA; obesity; prediabetes; sensitivity; specificity.