THE RELATIONSHIP BETWEEN TYPE-2 DIABETES AND TUBERCULOSIS

Area of Science:

• Immunology
• Endocrinology
• Microbiology

Background:

• Innate and adaptive immune disorders in Type 2 Diabetes (T2-D) increase susceptibility to Tuberculosis (TB).
• Metabolic dysregulation in T2-D compromises immune cell function, including neutrophils, macrophages, and NK cells.
• Hormonal changes and altered cytokine profiles (e.g., reduced TH1:TH2 ratio) in T2-D impact immune response to TB.

Purpose of the Study:

• To investigate the multifaceted immunological and physiological factors contributing to increased TB susceptibility in T2-D patients.
• To explore the roles of specific molecules like resistin and cytokines in the pathogenesis of TB in the context of T2-D.
• To examine the influence of endothelial function, microbiota alterations, and vitamin D status on TB comorbidity in T2-D.

Main Methods:

• Analysis of experimental and clinical data on immune responses in T2-D subjects.
• Assessment of cytokine levels (e.g., IFN-γ, IL-22, IL-17A, TNFα) and their correlation with TB.
• Evaluation of resistin levels, endothelial markers (ET-1), microbiota composition (SCFA-producing bacteria), and vitamin D status.

Main Results:

• T2-D is associated with compromised innate immunity, altered cytokine profiles (IFN-γ, IL-22 are key discriminators), and hormonal changes (ghrelin, leptin).
• Elevated resistin levels in T2-D reduce macrophage's ability to produce reactive oxygen species against TB; sputum endothelin-1 levels correlate with TB activity and treatment efficacy.
• T2-D exhibits altered microbiota with decreased SCFA-producing bacteria, and vitamin D deficiency is correlated with increased TB risk.

Conclusions:

• Immunological impairment, hormonal dysregulation, altered cytokine production, endothelial dysfunction, microbiota changes, and vitamin D deficiency are key contributors to TB comorbidity in T2-D.
• Specific biomarkers like resistin, endothelin-1, and certain cytokines (IFN-γ, IL-22) are significantly associated with TB pathogenesis and progression in T2-D.
• Targeting these factors may offer novel therapeutic strategies for managing TB in patients with T2-D.