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
Department of Medicine, Division of Pulmonary, Allergy And Critical Care Medicine
Bacterial Infections and Mycoses | Immunology and Infectious Disease | Infectious Disease | Microbiology | Nutritional and Metabolic Diseases | Therapeutics
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.
Diabetes mellitus, Matrix metalloproteinases, Mycobacterium tuberculosis
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DOI of Published Version
BMC Infect Dis. 2018 Jul 25;18(1):345. doi: 10.1186/s12879-018-3246-y. Link to article on publisher's site
BMC infectious diseases
Kumar NP, Moideen K, Viswanathan V, Shruthi BS, Sivakumar S, Menon PA, Kornfeld H, Babu S. (2018). 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. Open Access Publications by UMass Chan Authors. https://doi.org/10.1186/s12879-018-3246-y. Retrieved from https://escholarship.umassmed.edu/oapubs/3553
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This work is licensed under a Creative Commons Attribution 4.0 License.