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

• Published in: BMC infectious diseases 2019-12, Vol.19 (1), p.1039-1039, Article 1039
• Main Authors: Kumar, Nathella Pavan, Moideen, Kadar, Nancy, Arul, Viswanathan, Vijay, Shruthi, Basavaradhya S, Sivakumar, Shanmugam, Hissar, Syed, Kornfeld, Hardy, Babu, Subash
• Format: Article
• Language: English
• Subjects: Adult; Advanced glycosylation end products; Age; Aged; Antidiabetics; Antigens, Neoplasm - blood; Antitubercular Agents - therapeutic use; B cells; Case-Control Studies; Chromosomal proteins; Comorbidity; Comparative analysis; Diabetes; Diabetes mellitus; Diabetes Mellitus - blood; Diabetes Mellitus - drug therapy; Diabetes Mellitus - epidemiology; Drug therapy; Female; Glucose; Glycation End Products, Advanced - blood; Glycosylated hemoglobin; Glycosylation; Hemoglobin; Hemoglobins; HMGB1 protein; HMGB1 Protein - blood; Humans; Hyperglycemia; Hypoglycemic agents; Hypoglycemic Agents - therapeutic use; Immune system; Infectious diseases; Inflammation; Innate immunity; Ligands; Male; Metformin; Metformin - therapeutic use; Middle Aged; Mitogen-Activated Protein Kinases - blood; Morbidity; Mycobacterium tuberculosis; RAGE ligands; S100A12 Protein - blood; Therapy; Tuberculosis; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - epidemiology; Up-Regulation; X-rays
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-019-4648-1

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. 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). 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. 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.