TBC 024: Diabetes and Tuberculosis: A Bidirectional Challenge in Global Health

The interplay between diabetes mellitus (DM) and tuberculosis (TB) presents a significant challenge for global health, as both diseases independently and synergistically impair patient outcomes. The global rise in type 2 DM has heightened its association with TB, now rivaling human immunodeficiency virus (HIV) as a comorbid condition among TB patients. With the prevalence of DM expected to impact 629 million individuals by 2045, addressing the TB-DM dual burden is critical for disease control.

Immunological Mechanisms and Complications

DM contributes to chronic inflammation and immune dysfunction, driven by persistent hyperglycemia. Hyperglycemia disrupts both innate and adaptive immune responses, impairing macrophage phagocytosis, altering receptor expression, and reducing dendritic cell function. These changes compromise the immune response against Mycobacterium tuberculosis (Mtb). In TB-DM patients:

• Neutrophil counts are elevated but exhibit reduced phagocytic capacity, potentially serving as "Trojan horses" for Mtb.
• CD4+ and CD8+ T-lymphocyte counts are reduced, while Th1 and Th17 cell frequencies increase, disrupting cytokine balance and anti-TB immunity.
• Hyperglycemia sustains TB infection by exacerbating immune dysfunction and impairing glucose metabolism.

These immune alterations explain the increased susceptibility of DM patients to TB and the worsened outcomes observed in TB-DM cases.

Epidemiology and Risk Factors

Globally, DM increases the risk of TB incidence by 2-4 times and is associated with higher mortality rates during treatment. The comorbidity burden is particularly high in regions undergoing epidemiological transitions, where non-communicable diseases (NCDs) like DM compete for resources with communicable diseases (CDs) like TB. For example:

• In 2020, an estimated 370,000 new TB cases were attributable to DM.
• In Korea, 16.7% of adults had DM in 2020, with only 24.5% achieving optimal glycemic control. TB incidence in the same year was 44.6 per 100,000 people.

Prediabetes also plays a role, with individuals exhibiting increased interferon-gamma (IFN-γ) TB antigen responses, indicative of heightened immune activation. Poor glycemic control (PGC) significantly worsens TB prognosis, increasing the risks of treatment failure, relapse, and death.

Clinical Outcomes and Management

DM negatively impacts TB treatment outcomes, delaying microbiological response and reducing cure rates. Poorly controlled diabetes is associated with:

• Delayed culture conversion.
• Higher risks of relapse and drug resistance.
• Greater transmission potential due to higher Mtb bacterial loads.

Routine screening for DM in TB patients and glycemic control during TB treatment are crucial for optimizing outcomes. Evidence suggests that:

• Optimal glycemic control (OGC) enhances phagocytic activity, reduces adverse treatment outcomes, and improves bacterial clearance.
• Prolonged anti-TB treatment (up to 9 months) benefits patients with uncontrolled DM due to higher recurrence risks.
• Hypoglycemic drugs like metformin enhance TB treatment efficacy, improving sputum culture conversion and reducing mortality.

Pathophysiological Interactions

The bidirectional relationship between TB and DM further complicates disease management:

• TB exacerbates hyperglycemia by impairing liver and kidney functions, contributing to islet amyloidosis and glucose intolerance.
• Anti-TB drugs disrupt glucose homeostasis, with hyperglycemia influencing the pharmacokinetics of key medications like isoniazid and rifampicin.

Policy and Public Health Implications

The TB-DM intersection underscores the need for integrated healthcare approaches:

• Screening: Routine DM screening in TB clinics can identify undiagnosed cases, especially in high-burden settings where up to 50% of DM patients are unaware of their condition.
• Management: Combining stringent glucose control with anti-TB therapy improves treatment success rates and reduces complications.
• Education: Counseling patients on lifestyle modifications and monitoring prediabetes can prevent progression to DM.

The TB-DM comorbidity highlights the global epidemiological shift toward NCD dominance, necessitating a coordinated response that bridges CD and NCD frameworks. As TB and DM continue to pose mutual risks, enhanced surveillance, treatment strategies, and health education are vital for mitigating their combined burden.

See also: https://lintblab.weebly.com/publications.html

Source:

1. Magee, M.J., Trost, S.L., Salindri, A.D., Amere, G., Day, C.L. and Gandhi, N.R., 2020. Adults with Mycobacterium tuberculosis infection and pre-diabetes have increased levels of QuantiFERON interferon-gamma responses. Tuberculosis, 122, p.101935. https://tuberculosis101.blogspot.com/2024/10/adults-with-mtb-infection-and-pre-dm.html
2. Solanki HM, Ranpariya PN, Chudasama RK. Health status and treatment outcome of tuberculosis with diabetes mellitus cases, Rajkot City, Gujarat – A longitudinal study. Indian J Community Med 2023;48:75?81.
3. Peng, Y.F., 2023. Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management. Medicine International, 4(1), p.1-4.
4. Zhao, L., Gao, F., Zheng, C. and Sun, X., 2024. The impact of optimal glycemic control on tuberculosis treatment outcomes in patients with diabetes mellitus: systematic review and meta-analysis. JMIR Public Health and Surveillance, 10, p.e53948.
5. Kim KH, Kim HW, Kim YH, Park Y, Jung SS, Kim JW, et al. Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis. Respirology. 2024; 29(7): 624–632.