Elevated levels of matrix metalloproteinases reflect severity and extent of disease in tuberculosis-diabetes co-morbidity and are predominantly reversed following standard anti-tuberculosis or metformin treatment.

Kumar, N.P.; Moideen, K.; Viswanathan, V.; Shruthi, B.S.; Sivakumar, S.; Menon, P.A.; Kornfeld, H.; Babu, S .

BMC Infectious Diseases; 2018; 18(1); 345.

Abstract: Background: Matrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis – diabetes comorbidity (TB-DM) is not well understood.

Methods: To study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, -2, -3, -7, -8, -9, -10, -12 and-13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC).

Results: Circulating levels of MMP-1, -2, -3, -7, -10 and-12 were significantly higher in TB-DM compared to both TB and HC and MMP -13 levels were higher in comparison to HC alone. To understand the effect of standard anti-tuberculosis therapy (ATT) on these MMP levels in TB-DM, we measured the levels of MMPs at the end of treatment (post-treatment). Our findings indicate that ATT is associated with a significant reduction in the levels of MMP-1, -2, -3, -8 and-13 post-treatment. Moreover, the levels of MMP-1, -2, -3, -9 and-12 were significantly higher in TB-DM individuals with cavitary disease and/or bilateral disease at baseline but not post-treatment. Similarly, the levels of MMP -1, -2, -3 and-8 exhibited a significant positive relationship with bacterial burden and HbA1c levels at baseline but not post-treatment. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited significantly higher levels of MMP-1, -2, -10 and-12 at baseline and of MMP-1 and -3 post-treatment compared to those newly diagnosed with DM (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, -2, -3, -7, -9 and-12 at baseline and of MMP-7 post-treatment.

Conclusions: Our data demonstrate that systemic MMP levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.

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