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Systemic RAGE ligands are upregulated in tuberculosis individuals with diabetes co-morbidity and modulated by anti-tuberculosis treatment and metformin therapy

Kumar, Nathella Pavan
Moideen, Kadar
Nancy, Arul
Viswanathan, Vijay
Shruthi, Basavaradhya S.
Sivakumar, Shanmugam
Hissar, Syed
Kornfeld, Hardy
Babu, Subash
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Abstract

BACKGROUND: Ligands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated.

METHODS: We examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC).

RESULTS: Systemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens.

CONCLUSIONS: Our data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.

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BMC Infect Dis. 2019 Dec 9;19(1):1039. doi: 10.1186/s12879-019-4648-1. Link to article on publisher's site

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DOI
10.1186/s12879-019-4648-1
PubMed ID
31818258
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© The Author(s). 2019 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.