Epidemiology, pathogenesis and therapeutic management of PTB-DM [TB0105]

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Diabetes mellitus (DM) poses a significant health risk, leading to complications in multiple organs, including the lungs. Lung function is notably reduced in DM patients, with pulmonary complications commonly observed. The comorbidity of pulmonary tuberculosis (PTB) and DM is high, with a global prevalence of about 13.73%. PTB also raises the risk of developing DM, with higher DM prevalence in PTB patients compared to those without PTB. DM increases susceptibility to PTB by disrupting innate and adaptive immune responses, while PTB impairs islet cell function through islet amyloidosis. Anti-tuberculosis drugs further affect glucose homeostasis by disrupting liver and kidney functions.

Hyperglycemia in DM affects macrophage phagocytosis by altering recognition receptor expression, impairing immunity against PTB. Specifically, hyperglycemia reduces the phagocytic function of alveolar macrophages. Infection with Mycobacterium tuberculosis triggers dendritic cell maturation and migration, but in PTB-DM patients, baseline and post-treatment frequencies of plasmacytoid and myeloid dendritic cells are lower than in PTB-only patients. PTB-DM patients also exhibit elevated peripheral neutrophil counts, although these neutrophils have reduced phagocytic capacity, indicating compromised immunity.

The buildup of neutrophils may facilitate tuberculosis development, potentially acting as a "Trojan horse" for Mycobacterium tuberculosis. Additionally, natural killer cell levels in both peripheral blood and bronchoalveolar lavage fluid are significantly higher in PTB-DM patients than in PTB-only patients.

The proportion of CD4+ cells is significantly decreased in PTB-DM patients compared to household contacts. PTB-DM increases the frequency of Th1 and Th17 cells, indicating an altered immune response. Susceptibility to Mycobacterium tuberculosis infection is attributed to a defective Th1 cytokine response, and a compromised non-specific immune response may elevate infection risk in DM patients. In PTB-DM cases, an imbalance between Treg and effector T-cells is linked to immune dysfunction at infection sites. Hyperglycemia also reduces CD8+ T-lymphocyte counts in PTB-DM patients, impacting their functionality, as DM influences CD8+ T-cell function during latent TB infection by increasing Th2 and Th17 cell differentiation, thus disrupting anti-tuberculosis immunity.

Mycobacterium tuberculosis infection sustains hyperglycemia in DM patients, while PTB can impair glucose metabolism due to liver and kidney dysfunction from anti-tuberculosis therapy. Pancreatic amyloidosis is seen in TB-infected patients, with intense islet cell amyloidosis common in DM. Newly diagnosed PTB patients with DM or prediabetes show increased Mycobacterium tuberculosis bacterial load and higher transmission risk. Poor glucose control raises PTB risk and severity in DM patients, as evidenced by associations between blood glucose levels and computed tomography severity scores. PTB-DM patients have worse outcomes and poorer prognosis than those without DM, with poor glucose control linked to reduced treatment efficacy.

DM increases the risk of anti-tuberculosis treatment failure, persistence of positive TB cultures, and higher mortality rates in PTB patients. Mycobacterium tuberculosis utilizes escape mechanisms to avoid intracellular killing, which are exacerbated by hyperglycemia, further elevating the likelihood of treatment failure in PTB-DM patients. Poor glucose management increases the risk of pyrazinamide treatment failure, and DM influences the pharmacokinetics of isoniazid and rifampicin, reducing plasma concentrations by ~50%. Hypoglycemic drugs enhance anti-tuberculosis treatment efficacy in PTB-DM, with metformin notably improving sputum culture conversion after 2 months and significantly reducing mortality during anti-tuberculosis therapy.

Source: Peng, Y.F., 2023. Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management. Medicine International, 4(1), p.1-4.

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