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, Nathella P.; Moideen, Kadar; Viswanathan, Vijay; Shruthi, Basavaradhya S.; Sivakumar, Shanmugam; Menon, Pradeep A.; Kornfeld, Hardy; and Babu, Subash, "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" (2018). Open Access Articles. 3553.
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This work is licensed under a Creative Commons Attribution 4.0 License.