Type 2 diabetes mellitus associated microRNAs in tuberculosis susceptibility: a systematic review and bioinformatic analysis

Introduction: The coexistence of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) represents a growing global health challenge, particularly in low- and middle-income countries where TB remains endemic and T2DM prevalence is rising. Patients with T2DM exhibit a threefold higher risk of developing active TB and frequently present with more severe disease, including increased bacillary burden, delayed culture conversion, and higher relapse rates. These outcomes reflect the complex immunometabolic interactions between the two conditions. MicroRNAs (miRNAs), small non-coding regulators of post-transcriptional gene expression, emerge as potential biomarkers capable of integrating immune and metabolic processes. Methods: we conducted a systematic review of studies published between 2011 and 2025 in PubMed and Google Scholar, following PRISMA 2020 guidelines. Only studies involving adult human samples were included. Dysregulated miRNAs were standardized using miRBase and analyzed with miRNet v2.0, miRTarBase v9.0, and DIANA-miRPath v3.0. Interaction networks were constructed in Cytoscape, and functional enrichment analyses were performed using ClusterProfiler and MSigDB to identify shared pathways and gene targets. Results: The analysis revealed a set of miRNAs altered in both TB and T2DM, including hsa-miR-21, hsa-miR-29a-3p, hsa-miR-125a-5p, hsa-miR-125b, hsa-miR-130b, hsa-miR-144, hsa-miR-155, hsa-miR-223, and hsa-miR-486. These miRNAs converge on central target genes such as STAT3, PTEN, BCL2, MYC, RAF1, EGFR, IRS1, SMAD4, FOXO3, GLUT4, AKT1, and CTNNB1, regulating pathways of insulin signaling, glucose metabolism, apoptosis, inflammation, and fibrosis. Discussion: Shared miRNAs act as molecular nodes linking immunity and metabolism, providing a framework for biomarker development in TB-T2DM comorbidity. Their regulatory convergence suggests potential applications in diagnosis, prognosis, and therapeutic innovation, particularly in vulnerable populations where both diseases intersect. These findings underscore the importance of integrating immunometabolic biomarkers into personalized medicine strategies to address the dual burden of TB and T2DM.