Syndemic of TB and diabetes

Tuberculosis and diabetes mellitus have emerged as a syndemic, with each condition exacerbating the other. Patients with both diseases experience diagnostic challenges, as diabetes can significantly delay TB diagnosis and treatment initiation. For example, studies in China demonstrate a fourfold longer median time from symptom onset to first healthcare contact among people with diabetes. Although some reports suggest quicker treatment initiation, the weight of evidence supports delayed diagnosis as a common scenario.

Clinical presentations in patients with concurrent TB and diabetes are frequently more severe. These include disseminated disease, cavitary lesions, and atypical radiographic features that can further complicate diagnosis and management. Poor glycemic control correlates with worse disease severity, underscoring the need for meticulous monitoring of glucose levels throughout TB treatment. Notably, many patients without prior diabetes can develop transient hyperglycemia during therapy, raising questions about optimal screening and retesting intervals.

Treatment outcomes are consistently poorer in patients with diabetes. These individuals have higher mortality rates, greater risks of relapse, longer times to sputum conversion, and increased likelihood of multidrug-resistant TB. The interplay between diabetes and TB medications, along with the higher pill burden, increases the risks of adverse effects and treatment interruptions. Furthermore, hyperglycemia, whether transient or chronic, predicts worse TB outcomes, pointing to a complex interaction beyond simple glucose elevation.

At the biological level, M. tuberculosis infection of adipose tissue may drive metabolic disruptions that mimic the inflammatory state seen in insulin resistance. This mechanistic link provides a plausible explanation for the bidirectional relationship between TB and dysglycemia. Diabetes impairs both innate and adaptive immunity against TB, compromising the host’s ability to clear infection and leading to higher bacterial loads.

Emerging evidence suggests that certain diabetes medications, such as metformin and statins, may exert beneficial effects on TB immunopathology, independent of their glucose-lowering properties. However, corticosteroids and some TB treatments may worsen hyperglycemia, necessitating careful therapeutic balancing. There is a clear need for rigorous studies, including randomized controlled trials and standardized registries, to clarify these interactions and optimize treatment strategies.

Overall, the syndemic of TB and diabetes requires integrated management approaches that address not only microbial eradication but also metabolic and immunological dysfunction. Enhanced screening, prompt diagnosis, tailored treatment regimens, and close glycemic monitoring will be crucial to improving outcomes in this vulnerable population.

Source:

1. Magodoro, I., Kotze, L., Stek, C.J., West, A., Le Roux, A., Sobratee, N., Taliep, A., Hamada, Y., Dave, J.A., Rangaka, M.X. and Parihar, S.P., 2025. Clinical, metabolic and immune interaction between tuberculosis and diabetes mellitus: implications and opportunities for therapies. Expert Opinion on Pharmacotherapy.