Participants demographic and clinical data.

Drug-resistant (DR) tuberculosis (TB) and diabetes mellitus (DM) are intersecting epidemics that complicate management of both diseases and worsen patient outcomes. We conducted a prospective cohort study of 758 GeneXpert-confirmed pulmonary TB patients, of whom 75 had DM. Demographic, clinical, radiographic, and anthropometric data were collected at baseline. Sputum samples were cultured for mycobacterial isolation, and the obtained isolates were characterized for Mycobacterium tuberculosis complex (MTBC) lineage and drug-susceptibility testing using spoligotyping and microplate alamar blue assay. The TB-diabetes (TB-DM) comorbid cohort was older [TB-DM: 53/75 (70.7%) vs. 241/683 (35.3%) aged 41–60 years) (p < 0.001), included a higher proportion of females [TB-DM: 31/75 (41.3%) vs. TB-only: 150/683 (22.0%), p < 0.001], and had greater mean BMI (TB-DM: 23.36 ± 0.99 vs. TB-only: 19.97 ± 0.45 kg/m², p = 0.003). Analysis of 501 (TB-only: 448, TB-DM: 53) MTBC isolates revealed that TB-DM patients are more likely to get TB caused by L6 [TB-DM: 10/53 (18.9%) vs. TB-only: 37/448 (8.3%), p = 0.022] compared to the general TB population Lineage 4 [TB-DM: 36/53 (67.9%) vs. TB-only: 362/448 (80.8%), p = 0.046], Mycobacterial strains from TB-DM exhibited higher isoniazid mono-resistance [TB-DM: 15/50 (30.0%) vs. 42/288 (14.6%), p = 0.012] and harbored more multidrug-resistant TB [TB-DM: 5/50 (10.0%) vs. TB-only: 16/288 (5.6%), p = 0.215] although this did not reach statistical significance. These findings indicate that DM not only predisposes individuals to TB but may also shift the spectrum of infecting lineages and promotes the emergence of DR strains. Integrated TB-DM screening, lineage-aware diagnostics, and tailored treatment protocols are urgently needed in high-burden settings to address this dual threat.