Diabetes Mellitus (DM) and Tuberculosis (TB) Interactions

Epidemiological Link

• Prevalence: 1 in 10 adults has diabetes (DM), increasing TB risk.
• Co-Infection Risk:Active TB risk ~3x higher in DM patients.Latent TB infection (LTBI) risk ~2x higher.Increased recurrence, treatment failure, and mortality rates in DM-TB co-infection.
• Global Context: DM-TB burden disproportionately affects Asians (55%) compared to Caucasians (22%) and Blacks (23%).

Immunological Effects

• Innate Immunity:Chronic hyperglycemia impairs macrophage and dendritic cell function.Decreased phagocytosis, antigen presentation, and immune cell recruitment.Increased inflammatory neutrophil response worsens bacterial load.
• Adaptive Immunity:Delayed CD4+ and CD8+ T-cell activation reduces IFN-γ secretion.Altered cytokine profiles:Increased Th1/Th17 cytokines (IFN-γ, TNF-α, IL-17).Suppressed Th2 cytokines, lowering bacterial clearance.Reduced cytotoxic markers (perforin, granzyme B) in CD8+ T cells.
• Cytokine Production:Lower IL-1β and IL-8 impair monocyte phagocytic function.Regional differences observed in cytokine responses.

Pathophysiological Mechanisms

• Macrophage Polarization:Hyperglycemia induces M2 polarization, reducing bactericidal activity.Medications like glimepiride may exacerbate M2 polarization.
• Oxidative Stress:Elevated reactive oxygen species (ROS) and advanced glycation end-products (AGEs) damage immune functions.Antioxidants (e.g., resveratrol) and metformin mitigate oxidative stress.
• Efflux Pumps:Increased efflux pump expression in DM patients contributes to drug resistance.

Diagnostic and Treatment Challenges

• Diagnostic Tools:Tuberculin Skin Test (TST) has lower specificity due to cross-reactions.Interferon-Gamma Release Assay (IGRA) is more specific but less sensitive in DM patients.Emerging diagnostic methods: TrueNat, CB-NAAT, Line Probe Assay, and CAD4TB software.
• Treatment Interactions:Rifampicin interacts with antidiabetic drugs, necessitating careful glucose monitoring.Metformin shows promise in enhancing anti-TB treatment by inducing ROS and reducing inflammation.

Integrated Management Strategies

• Public Health Implications:Poor glycemic control significantly increases TB risk (155.5 per 100,000 person-years for poorly controlled DM).Better glycemic control could prevent ~7.5% of TB cases.
• Therapeutic Advances:Host-Directed Therapy (HDT) options like metformin improve TB outcomes.Emerging treatments target nutrient-sensing pathways (e.g., SIRT1, AMPK) to combat DM and TB.

Challenges in Low-Resource Settings

• India's Burden:High incidence of TB, with 24% of cases undiagnosed.Significant MDR-TB prevalence and urban overcrowding exacerbate transmission.
• Interventions:Active Case Finding (ACF) and financial incentives for treatment adherence.Collaboration across sectors needed for holistic TB-DM management.

Conclusion

• DM-TB comorbidity represents a dual burden requiring integrated care strategies.
• Effective glycemic control, early TB diagnosis, and advanced therapeutic interventions are critical to mitigating the impact of these interlinked conditions.

References:

1. Ye, Z., Li, L., Yang, L., Zhuang, L., Aspatwar, A., Wang, L. and Gong, W., 2024. Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective. In Exploration (p. 20230138).
2. Al-Bari MAA, Peake N, Eid N. Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges. World J Diabetes 2024; 15(5): 853-866.
3. Byers, M.; Guy, E. The Complex Relationship Between Tuberculosis and Hyperglycemia. Diagnostics 2024, 14, 2539.
4. Lee P-H, Fu H, Lai T-C, Chiang C-Y, Chan C-C, Lin H-H (2016) Glycemic Control and the Risk of Tuberculosis: A Cohort Study. PLoS Med 13(8): e1002072.
5. Vaishya R, Misra A, Vaish A, Singh SK. Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges. J Diabetes. 2024 May;16(5):e13427. doi: 10.1111/1753-0407.13427.
6. Khanna, A., Saha, R. and Ahmad, N., 2023. National TB elimination programme-what has changed. Indian Journal of Medical Microbiology, 42, pp.103-107.

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