Diabetes and Tuberculosis Interplay in Several Countries

Tuberculosis (TB) patients with diabetes mellitus (DM) are generally older, more often male, and exhibit higher rates of comorbidities such as hypertension and cardiovascular disease compared to non-diabetic TB patients. Despite these differences, there are no significant variations in symptoms, radiographic findings, or prevalence of acid-fast bacilli (AFB) positivity between controlled diabetics and non-diabetics. However, uncontrolled diabetic TB patients show higher rates of cavitary lesions and AFB positivity on sputum smears, reaching 65.8%, compared to 40.4% in non-diabetics. Poor glycemic control correlates with more severe disease manifestations, extended treatment durations, and increased risk of treatment failure and mortality.

The interaction between TB and DM is complex, with hyperglycemia impairing immune responses, including neutrophil function and adaptive immunity, thereby increasing susceptibility to TB. Uncontrolled diabetes quadruples the likelihood of TB diagnosis and exacerbates disease severity. The bidirectional relationship between TB and DM is evident as active TB can induce hyperglycemia, potentially leading to DM, while pre-existing DM worsens TB outcomes. Effective management of both conditions is critical to mitigating adverse effects, as improved TB treatment has been shown to normalize glucose levels in some cases.

A study at the Instituto Brasileiro para a Investigação da Tuberculose (IBIT) highlighted the significant association between glucose metabolism disorders (GMD) and TB. Among 892 participants, 63.1% exhibited elevated HbA1c levels, with 80% of pulmonary TB (PTB) cases showing abnormal glucose metabolism at diagnosis. Regression analyses confirmed that uncontrolled DM, especially in smokers, significantly increased TB risk. Poor glycemic control (HbA1c ≥7.0%) was a strong predictor of TB, and smokers with uncontrolled DM had an adjusted odds ratio of 6.3 for TB development.

Globally, TB remains a leading health challenge, with 10.4 million new cases and 1.7 million deaths reported in 2016, predominantly in low- and middle-income countries. DM, now a growing epidemic in these regions, compounds the burden, increasing the risk of TB incidence, treatment failure, and relapse. The interplay between TB and metabolic disorders extends beyond glucose metabolism, with TB-induced inflammation and epigenetic changes potentially increasing DM risk. Prospective studies are needed to clarify these mechanisms and guide interventions.

TB also poses long-term risks to respiratory and cardiovascular health. Post-TB complications such as cavitation, fibrosis, and bronchiectasis increase the risk of chronic lung diseases, including COPD, and cardiovascular events such as ischemic stroke. Distinguishing direct effects of TB from pre-existing risk factors is challenging but underscores the need for integrated care approaches.

A South Korean cohort study (2011–2018) further illustrated the compounded vulnerabilities of TB-DM patients, who were older, predominantly male, and had worse treatment outcomes, including higher mortality rates. TB was the leading cause of death in this group, while non-TB-related deaths were primarily due to lung cancer and pneumonia. Factors like advanced age, low income, and higher comorbidity scores were linked to poorer outcomes, emphasizing the need for targeted interventions.

A 2018 cross-sectional study in three geographic communities revealed disparities in pre-diabetes (PDM) and latent TB infection (LTBI). Urban areas had higher PDM prevalence, while rural settings had more LTBI cases. Logistic regression identified older age, smoking, lack of BCG vaccination, and abdominal obesity as significant predictors of PDM and LTBI. BCG vaccination notably reduced the risk of concurrent PDM-LTBI, underscoring its protective role.

Efforts to reduce TB-DM burdens must address the dual epidemic's challenges through integrated management strategies, large-scale clinical trials, and targeted interventions. Strengthening TB-DM care, especially in resource-limited settings, is essential to achieving global TB elimination goals.

See also: https://lintblab.weebly.com/research-topics.html

References:

1. Park, S.W., Shin, J.W., Kim, J.Y., Park, I.W., Choi, B.W., Choi, J.C. and Kim, Y.S., 2012. The effect of diabetic control status on the clinical features of pulmonary tuberculosis. European journal of clinical microbiology & infectious diseases, 31, pp.1305-1310.
2. Almeida-Junior JL, Gil-Santana L, Oliveira CAM, Castro S, Cafezeiro AS, Daltro C, et al. (2016) Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil. PLoS ONE 11(4):e0153590.
3. Zhao, L., Fan, K., Sun, X., Li, W., Qin, F., Shi, L., Gao, F. and Zheng, C., 2024. Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus. Frontiers in Immunology, 14, p.1305325.
4. Magee, M.J., Salindri, A.D., Gujral, U.P., Auld, S.C., Bao, J., Haw, J.S., Lin, H.H. and Kornfeld, H., 2018. Convergence of non-communicable diseases and tuberculosis: a two-way street?. The International Journal of Tuberculosis and Lung Disease, 22(11), pp.1258-1268.
5. Bao, J., Hafner, R., Lin, Y., Lin, H.H. and Magee, M.J., 2018. Curbing the tuberculosis and diabetes co-epidemic: strategies for the integration of clinical care and research. The International Journal of Tuberculosis and Lung Disease, 22(10), pp.1111-1112.
6. Kwak SH, Jeong D, Mok J, Jeon D, Kang H-Y, Kim HJ, et al. (2023) Association between diabetes mellitus and cause of death in patients with tuberculosis: A Korean nationwide cohort study. PLoS ONE 18(12): e0295556.
7. Akinshipe, B.O., Yusuf, E.O., Akinshipe, F.O., Moronkeji, M.A. and Nwaobi, A.C., 2019. Prevalence and Determinants of Pre-diabetes and Latent Tuberculosis Infection Among Apparently Healthy Adults in Three Communities in Southern Nigeria. International Journal of Immunology, 7(2), pp.23-32.

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