Hyperglycemia, Glycemic Control, and the Risk of Tuberculosis

Diabetes mellitus (DM) is a complex disease caused by insufficient insulin production, insulin resistance, or both. It leads to chronic hyperglycaemia and is associated with impaired insulin secretion and tissue resistance to insulin, particularly in muscle, liver, and fat. Insulin resistance can result from genetic factors, fetal malnutrition, and increased visceral fat. Globally, DM affects hundreds of millions, with prediabetes (PDM) representing a high-risk state for progression. PDM is often silent, marked by elevated blood glucose but below diabetic thresholds, and is projected to rise significantly in prevalence by 2030.[1] See also: https://tbreadingnotes.blogspot.com/2024/10/glycemic-control-in-tuberculosis-tb0090.html

Both DM and PDM are linked to chronic low-grade inflammation, which contributes to their development and progression by promoting organ dysfunction, hyperglycaemia, and insulin resistance. This inflammation may also alter immune responses, increasing susceptibility to infections such as tuberculosis (TB). Elevated glucose and persistent inflammation can impair immune function, with some researchers considering DM not only a metabolic but also an immune-mediated disease.[1] See also: https://tbreadingnotes.blogspot.com/2024/10/recent-advances-in-treatment-of.html

Recent studies have explored the immune profiles of individuals with both PDM and TB, but findings remain inconsistent. Some research reports heightened levels of both pro- and anti-inflammatory cytokines in TB patients with PDM, suggesting increased immune activation. Other studies show reduced cytokine levels in people with latent TB and PDM, indicating a dampened immune response. These conflicting results highlight the need for further investigation into how PDM and DM influence immunity, particularly in the context of TB.[1]

When Mycobacterium tuberculosis infection coincides with hyperglycemia, the immune response may be further compromised, increasing the risk of TB progression. TB itself can induce temporary hyperglycemia in many patients, with glucose levels often normalizing after successful TB treatment. However, in a subset of individuals, persistent hyperglycemia remains, suggesting that TB may unmask undiagnosed diabetes, worsen preexisting metabolic dysfunction, or contribute to diabetes onset. The exact mechanisms underlying this association remain unclear but likely involve chronic inflammation, altered cytokine signaling, and immune dysfunction, all of which can impact glucose metabolism.[2]

Beyond the immediate effects on glucose regulation, individuals with prediabetes or intermediate hyperglycemia have an elevated risk of developing TB, similar to those with diagnosed diabetes. Even mild glucose imbalances may impair immune defenses, increasing susceptibility to TB infection. Moreover, patients with both TB and diabetes face worse outcomes, including a higher risk of treatment failure, prolonged disease progression, and complications. This highlights the urgent need for integrated management strategies that address both TB and diabetes, ensuring comprehensive screening, early intervention, and tailored treatment plans to improve patient outcomes.[2]

Poorly controlled diabetes not only increases susceptibility to TB infection but also worsens treatment outcomes, including higher rates of relapse and mortality. Chronic hyperglycemia impairs both innate and adaptive immune responses, reducing the ability to contain Mycobacterium tuberculosis and compromising granuloma integrity. As a result, individuals with persistent hyperglycemia are more prone to developing active TB and less likely to achieve successful treatment outcomes. This highlights the need for clinicians to closely monitor and manage blood glucose levels in patients at risk for or undergoing treatment for TB.[3]

Integrated screening and management programs targeting both diabetes and TB are essential, particularly in regions with high burdens of both diseases. Regular screening for TB in diabetic patients, especially those with poor glycemic control, should be prioritized. Likewise, TB patients should be evaluated for glucose dysregulation early in the course of treatment. Public health strategies focusing on diabetes prevention and optimal glycemic control can play a vital role in reducing TB incidence. Addressing these overlapping epidemics through coordinated care models not only improves individual outcomes but also contributes to broader efforts in TB control and eradication.[3]

References:

1. Abbas, U., Masood, K.I., Khan, A., Irfan, M., Saifullah, N., Jamil, B. and Hasan, Z., 2022. Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries. Journal of clinical tuberculosis and other mycobacterial diseases, 29, p.100343.

2. Byers, M.; Guy, E. The Complex Relationship Between Tuberculosis and Hyperglycemia. Diagnostics 2024, 14, 2539.

3. Lee P-H, Fu H, Lai T-C, Chiang C-Y, Chan C-C, Lin H-H (2016) Glycemic Control and the Risk of Tuberculosis: A Cohort Study. PLoS Med 13(8): e1002072.