Anuradha Rajamanickam ^1* Sanaadhan P. Kothandaraman ² PavanKumar Nathella ³ Dr Vijay Viswanathan ⁴ Siva Kumar Shanmugam ³ Syed Hissar ³ Sujatha Nott ⁵ Hardy Kornfeld ⁶ Subash Babu ^1,7

• ¹ International Centers for Excellence in Research (ICER), Chennai, India
• ² Stanley Medical College, Chennai, Tamil Nadu, India
• ³ National Institute of Research in Tuberculosis (ICMR), Chennai, Tamil Nadu, India
• ⁴ Prof. M. Viswanathan Diabetes Research Center, Chennai, Tamil Nadu, India
• ⁵ Infectious Diseases, Dignity Health, Chandler, AZ, USA, Chandler, United States
• ⁶ University of Massachusetts Medical School, Worcester, Massachusetts, United States
• ⁷ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States

Introduction: Tuberculosis (TB) remains a significant health concern in India, and its complexity is exacerbated by the rising occurrence of non-communicable diseases such as diabetes mellitus (DM). Recognizing that DM is a risk factor for active TB, the emerging comorbidity of TB and PDM (TB-PDM) presents a particular challenge. Our study focused on the impact of PDM on cytokine and chemokine profiles in patients with pulmonary tuberculosis TB) who also have PDM. Materials and Methods: We measured and compared the cytokines (GM-CSF, IFN-γ, IL-1α/IL-1F1, IL-1β/IL-1F2, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17/IL-17A, IL-18/IL-1F4, TNF-α) and chemokine (CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL9, CXCL10, and CXCL11) levels in plasma samples of TB-PDM, only TB or only PDM using multiplex assay. Results: We observed that PDM was linked to higher mycobacterial loads in TB. Patients with coexisting TB and PDM showed elevated levels of various cytokines (including IFNγ, TNFα, IL-2, IL-17, IL-1α, IL-1β, IL-6, IL-12, IL-18, and GM-CSF) and chemokines (such as CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL9, CXCL10, and CXCL11). Additionally, cytokines such as IL-18 and GM-CSF, along with the chemokine CCL11, were closely linked to levels of glycated hemoglobin (HbA1c), hinting at an interaction between glycemic control and immune response in TB patients with PDM. Conclusion: Our results highlight the complex interplay between metabolic disturbances, immune responses, and TB pathology in the context of PDM, particularly highlighting the impact of changes in HbA1c levels. This emphasizes the need for specialized approaches to manage and treat TB-PDM comorbidity.