Hyperglycemia, Glycemic Control, and the Risk of Tuberculosis

When Mycobacterium tuberculosis bacilli are inhaled, they enter the alveoli of the lungs where they initially infect local macrophages. If these macrophages fail to destroy the bacteria, the bacilli multiply, leading to the death and rupture of the macrophages. This releases more bacilli which are then engulfed by other immune cells, notably dendritic cells. These dendritic cells transport the bacteria to the thoracic lymph nodes, where they initiate the adaptive immune response by presenting antigens to T lymphocytes.[1] See also: https://tbreadingnotes.blogspot.com/2024/10/recent-advances-in-treatment-of.html

This immune activation leads to the development of T-cell mediated immunity, with memory T helper 1 cells secreting interferon-gamma (IFNγ), which enhances the immune response. This cytokine activity helps in forming granulomas, structures that contain and attempt to neutralize the infection. The outcome of this immune response can take one of three paths:[1]

1. Complete Clearance: The immune system effectively eradicates the bacteria. See also: https://tbreadingnotes.blogspot.com/2024/10/glycemic-control-in-tuberculosis-tb0090.html
2. Latent TB Infection (LTBI): Here, the granuloma contains the bacteria but does not eliminate them, leading to a dormant state where the infection is not active but can reactivate later. 
3. Active TB: If the immune response fails to control the pathogen, the bacteria continue to multiply, causing active tuberculosis disease. 

Epidemiological research has established a concerning link where tuberculosis (TB) can precipitate hyperglycemia. At the time of TB diagnosis, many patients exhibit intermediate hyperglycemia, suggesting that TB might induce or aggravate glycemic imbalances. Intriguingly, the course of this hyperglycemia following TB treatment varies. A significant number of patients see their glucose levels return to normal post-treatment, indicating that TB might be a reversible cause of hyperglycemia in these cases.[1]

However, the response is not uniform; between 10% to 50% of individuals continue to suffer from persistent hyperglycemia even after TB has been treated. This suggests a complex interaction where TB could either unveil latent diabetes, exacerbate existing diabetes, or lead to a new onset of diabetes-like conditions.[1]
Moreover, individuals with intermediate hyperglycemia or pre-diabetes are found to have an increased prevalence of TB, mirroring the risk seen in those with diagnosed diabetes mellitus. This indicates that even mild glucose dysregulation can compromise the immune response to TB, increasing susceptibility. Additionally, patients who have both TB and diabetes mellitus face a significantly elevated risk of treatment failure for TB, complicating the management of both conditions. This dual burden emphasizes the need for integrated care strategies focusing on both TB control and diabetes management to prevent adverse outcomes.[1]
Diabetes Mellitus (DM) significantly heightens the risk of developing active tuberculosis (TB), alongside increasing the chances of treatment failure, relapse, and mortality in TB patients. A comprehensive study conducted in New Taipei City from 2005 to 2008, which followed adults over the age of 30 until 2012, aimed to explore this relationship. Participants were screened for various chronic diseases including diabetes. Among the 122,042 participants with available fasting plasma glucose (FPG) data, 9.2% were identified with DM at the start of the study, with a notable 71.2% of these diabetic individuals exhibiting poor glycemic control, defined by an FPG greater than 130 mg/dl.[2]
The findings indicated stark differences in TB incidence rates: 54.2 per 100,000 person-years for those without diabetes, 65.1 for diabetics with good control, and a significantly higher rate of 155.5 for those with poor control. Kaplan-Meier survival analysis further highlighted that TB-free survival was significantly lower among individuals with poorly controlled diabetes. Multivariable Cox regression analysis confirmed that the risk of developing TB was markedly higher in diabetic patients, especially those with poor glycemic control, compared to non-diabetics.[2]
Importantly, the study did not find significant modifications to this association based on sex or body mass index (BMI). It was calculated that by improving glycemic control among all diabetic patients, approximately 7.5% of TB cases could potentially be prevented. These results underscore the importance of effective diabetes management in controlling TB. The study advocates for a multifaceted approach to public health involving prevention of diabetes, early detection, meticulous glycemic control, and integrated screening strategies for both diabetes and TB to mitigate the risk and impact of TB in diabetic populations.[2]

References:

1. Byers, M.; Guy, E. The Complex Relationship Between Tuberculosis and Hyperglycemia. Diagnostics 2024, 14, 2539. https://doi.org/10.3390/diagnostics14222539

2. 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. doi:10.1371/journal.pmed.1002072