Additionally, ceRNA networks and dual-luciferase assays confirmed that novel-miR-109 inhibits the translation of FPR1, LILRB3, and MSTRG.4908.1, while hsa-miR-4726-5p targets the 3' UTR of SECTM1.<h4>Conclusions</h4>This study establishes a validated multi-omics framework for the early detection of T2DM-TB, elucidates key regulatory axes (IRF1/IFN-γ, ceRNA circuitry, CXCL10/CXCL6), and provides actionable biomarkers and high-performance models for precision intervention in T2DM-TB management. Here, CXCL6 is linked to type 2 diabetes mellitus.