Effect of anti-tuberculosis treatment on the systemic levels of tissue inhibitors of metalloproteinases in tuberculosis – Diabetes co-morbidity

OBJECTIVES: To study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT). METHODS: We examined the levels of TIMP-1, -2, -3 and -4 in pulmonary tuberculosis alone (TB) or TB-DM at baseline and after ATT. RESULTS: TIMP-1, -3 and -4 were significantly increased in TB-DM compared to TB at baseline and after ATT. ATT resulted in a significant reduction in TIMP-2 and -3 levels and a significant increase in TIMP-1 in both TB and TB-DM. TIMP-1, -3 and -4 were also significantly increased in TB-DM individuals with bilateral, cavitary disease and also exhibited a positive relationship with bacterial burden in TB-DM and HbA1c in all TB individuals. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited higher levels of TIMP-1, -2, -3 and -4 at baseline and TIMP-2 at post-treatment compared to those newly diagnosed with DM (NDM). KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment. CONCLUSIONS: TIMP levels were elevated in TB-DM, associated with disease severity and bacterial burden, correlated with HbA1c levels and modulated by duration of DM and metformin treatment.