Type 2 diabetes mellitus is associated with distinct post-treatment metabolic profiles in pulmonary tuberculosis

Type 2 diabetes mellitus (T2DM) is a major risk factor for pulmonary tuberculosis (PTB), exacerbates disease severity and reduces the efficacy of anti-tuberculosis therapy. Previous studies have shown that T2DM is associated with exacerbated metabolic disturbances in patients with PTB. However, metabolic differences between PTB patients with comorbid T2DM (PTB-DM) and those with PTB after anti-TB therapy remain unclear.

Untargeted metabolomic analysis was conducted on plasma samples collected from April 2024 to November 2025 at Tianjin Haihe Hospital, China. A total of 75 participants were enrolled, including healthy controls, patients with newly diagnosed drug-sensitive PTB, patients with PTB-DM, as well as two independent post-treatment groups sampled after 6 months of standard anti-TB therapy: patients with PTB and patients with PTB-DM.

Patients with PTB exhibited marked metabolic disturbances, particularly in tyrosine metabolism and steroid hormone biosynthesis. Patients with PTB-DM showed broader metabolic reprogramming, including changes in arginine and proline metabolism, steroid hormone biosynthesis, cAMP signaling, and taurine and hypotaurine metabolism. After 6 months of standard therapy, the PTB_6M group showed treatment-associated metabolic differences, especially in bile acid metabolism, suggesting partial normalization of several metabolic features. In contrast, patients with PTB-DM after treatment showed persistent metabolic abnormalities involving sphingolipid, purine and biotin metabolism. Notably, 12-HETE and 12-HHTrE showed elevated levels in active PTB, decreased levels after treatment, but remained relatively higher in PTB-DM after treatment.

This study offers an integrated assessment of metabolic alterations in PTB and PTB-DM, suggesting that comorbid T2DM is associated with broader metabolic dysregulation during active PTB and persistent post-treatment metabolic abnormalities.