Circular RNAs as diagnostic biomarkers in type 2 diabetes mellitus: implications in metabolic dysfunction and immune-inflammatory crosstalk.

Type 2 diabetes mellitus (T2DM) is a metabolically heterogeneous disease for which current approaches to early diagnosis and risk stratification remain limited. Circular RNAs (circRNAs) have emerged as promising molecular candidates because of their stability, disease relevance, and regulatory versatility. Circular RNAs (circRNAs) have emerged as a promising class of non-coding RNAs that exhibit unique advantages, such as high stability, disease specificity, and the ability to act as regulators in competing endogenous RNA (ceRNA) networks. This review summarizes the current understanding of circRNAs in T2DM, highlighting their potential as diagnostic biomarkers and their roles in metabolic dysfunction. We explore how circRNAs contribute to key pathogenic processes in T2DM, including insulin resistance, glucose uptake, β-cell survival, inflammation, and vascular dysfunction. Additionally, we discuss the challenges in circRNA research, including technical biases, cohort heterogeneity, and the need for rigorous mechanistic validation. The review concludes by outlining future directions for circRNA-based research, including multicenter prospective studies, single-cell and spatial transcriptomic integration, and the development of circRNA-based companion diagnostics for precision medicine in T2DM.