Navigating the dual burden of diabetes mellitus and tuberculosis: A comprehensive review of clinical and public health strategies

The intersection of diabetes mellitus (DM) and tuberculosis (TB) constitutes a significant global health challenge, marked by complex disease interactions with profound clinical and public health consequences. TB, a historically prevalent infectious disease, and DM, a rising non-communicable disease, together fuel a syndemic in which each condition exacerbates the other. DM increases susceptibility to TB by weakening immune defenses, facilitating the proliferation of Mycobacterium tuberculosis (MTB) and accelerating TB progression. Mechanistic insights reveal that hyperglycemia-driven immune dysfunction impairs both innate and adaptive immunity, with effects such as reduced T-helper cell activity, impaired macrophage and neutrophil responses, and altered cytokine profiles. These immune changes allow for easier MTB survival, lung damage, and systemic inflammation, thus worsening TB outcomes in diabetic patients. The combined burden of TB and DM disproportionately impacts vulnerable populations, particularly in resource-limited settings and developing nations where TB remains endemic, and diabetes prevalence is increasing. Population health data highlight the increasing occurrence of DM among TB patients, with studies reporting comorbidity rates as high as 45 % in some regions. Furthermore, TB worsens glycemic control in DM patients, creating a cyclical burden that complicates disease management. Evidence also highlights the role of social and demographic characteristics, including age, urban residence, and financial standing, along with behavioral factors like tobacco and alcohol use, as significant risk enhancers for TB-DM comorbidity. Screening for tuberculosis in individuals with diabetes and for diabetes in those with tuberculosis is crucial in high-burden regions to enable timely detection and intervention. Effective screening methods include clinical assessments, radiological imaging, and both rapid and conventional microbiological testing for TB, while plasma glucose and glycosylated hemoglobin (HbA1c) tests are standard for detecting diabetes. Latent tuberculosis utilizing the Mantoux tuberculin skin test or interferon-gamma release assays (IGRAs) for screening is particularly recommended for high-risk diabetic patients to help prevent the progression of the disease. These dual screening efforts are essential for reducing morbidity, mortality, and the transmission of TB among individuals with diabetes. Therapeutic strategies for TB-DM management involve tailored anti-diabetic regimens and cautious selection of anti-TB medications to avoid adverse interactions. Insulin is the preferred treatment for severe cases of diabetes in TB patients due to its anabolic properties and lack of interaction with TB medications. Oral agents like metformin are widely used in mild cases but require monitoring for renal and hepatic health. Innovative approaches and meticulous monitoring can improve TB outcomes in DM patients by achieving better glycemic control. Meanwhile, challenges persist due to the risk of drug resistance, complications from multi-drug-resistant TB, and heightened mortality. In conclusion, TB-DM comorbidity calls for an integrated healthcare response, combining individualized treatment with strengthened health systems and public health policies. Addressing the "syndemic" of TB and DM requires targeted screening, synchronized management protocols, and sustained community-based interventions. Integrating these strategies with better healthcare access and policy reforms can help reduce the burden of TB-DM and improve outcomes for affected populations globally.