Latent tuberculosis infection (LTBI), marked by Mycobacterium tuberculosis (M.tb) infection without active disease, affects about one-fourth of the global population, serving as a reservoir for TB reactivation, especially under conditions such as age and co-morbidities like diabetes mellitus (DM). M.tb persistence is largely due to immune responses involving T cells, especially CD4+ and CD8+ cells, which support macrophage granuloma formation and antigen response. DM impacts this immune function, diminishing cytokine production (e.g., IFN-γ, TNF-α, IL-17) and impairing macrophages, monocytes, and dendritic cells, which in turn fosters inflammation and increases TB risk.
In individuals with both LTBI and DM, innate and adaptive immune responses show alterations: lower frequencies of dendritic cells, altered monocyte profiles, and reduced levels of γδ T cells, NK, and iNKT cells. Adaptive immunity also suffers, with lower Th1, Th2, and Th17 cells following TB antigen exposure, and altered B cell profiles, indicating compromised immune responsiveness and greater susceptibility to active TB. These changes are partly mediated by inflammatory markers and cytokines (e.g., IL-10, TGF-β), with elevated metabolic markers (e.g., leptin, PAI-1) indicating metabolic stress.
DM severity, marked by factors like insulin usage, duration, cardiovascular disease, and chronic kidney disease, correlates with increased TB risk, suggesting targeted screening for high-risk DM patients. Hyperglycemia impairs monocyte function, limits dendritic cell differentiation, and polarizes macrophages toward less effective anti-mycobacterial states, increasing susceptibility to M.tb. Delays in adaptive immune activation, especially CD4+ and CD8+ T cells, further weaken TB defenses in DM patients. Pulmonary TB (PTB) lesions are more severe in DM patients, with increased inflammatory responses but reduced capacity to clear bacteria.
Additionally, socioeconomic factors and barriers impact TB care, as DM-TB patients in low-resource settings often face significant economic hurdles that disrupt diagnosis and treatment adherence. Strategies such as cash transfers and social protections can improve TB outcomes by reducing financial burdens and facilitating access to care. Universal social protections and decentralized treatment approaches have shown potential in reducing TB loss to follow-up (LTFU) rates, particularly among vulnerable groups like migrants, those with low incomes, and individuals with high out-of-pocket healthcare costs.
In summary, DM complicates TB immunity, heightening the risk of LTBI reactivation and active TB progression. Addressing these challenges requires integrated clinical, economic, and social interventions to support comprehensive TB care, especially in high-risk, resource-limited populations.
References:
Kumar, N.P., & Babu, S. (2023). Impact of diabetes mellitus on immunity to latent tuberculosis infection. Frontiers in Clinical Diabetes and Healthcare, 4, 1095467.
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).
Kang, J.Y., Han, K., Lee, S.H. and Kim, M.K., 2023. Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up. Respiratory Research, 24(1), pp.1-9.
Shete, P.B., Kadota, J.L., Nanyunja, G., Namale, C., Nalugwa, T., Oyuku, D., Turyahabwe, S., Kiwanuka, N., Cattamanchi, A. and Katamba, A., 2023. Evaluating the impact of cash transfers on tuberculosis (ExaCT TB): a stepped wedge cluster randomised controlled trial. ERJ open research, 9(3).
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