Cytokine and chemokine profiles in pulmonary TB with Dysglycemia

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, significantly increases susceptibility to tuberculosis (TB) and worsens outcomes in active disease. T2DM impairs immune responses through mechanisms such as chronic inflammation, advanced glycation end products (AGEs), and oxidative stress, which promote Mtb survival and spread. These impairments reduce the functionality of key immune cells like macrophages and dendritic cells, alter cytokine profiles, and increase pro-inflammatory states. Poor glycemic control further exacerbates these issues, increasing the risk of latent TB progression to active disease and contributing to higher rates of multidrug-resistant TB (MDR-TB) and poor treatment outcomes.[3]

In T2DM, immune dysregulation is compounded by metabolic disturbances, such as gut microbiome dysbiosis, which weakens immune responses and impacts TB progression. Emerging therapies like metformin show promise in improving immune function and reducing inflammation, while specific biomarkers, including cytokine levels and metabolite ratios, offer potential for better TB diagnosis and management in T2DM patients. These insights highlight the critical interplay between metabolic and immune systems in controlling TB and the importance of tailored strategies to improve outcomes in individuals with T2DM.[3]

Elevated Biomarkers in TB-PDM:

• Individuals with TB-PDM showed higher levels of HbA1c, random blood glucose, and total cholesterol compared to those with TB alone or PDM alone. See also: Lin TB Lab

Bacterial Load:

• TB-PDM patients exhibited significantly higher bacterial loads, as evidenced by acid-fast bacillus staining and culture results. See also: Health care visit and TB

Cytokine Levels:

• Type 1 cytokines (e.g., IFN-γ, TNF-α, IL-2) and the type 17 cytokine IL-17 were substantially elevated in TB-PDM compared to TB or PDM groups.
• Anti-inflammatory IL-10 levels were higher in TB-PDM than in TB or PDM alone. See also: Glycemic control and TB
• Pro-inflammatory cytokines (e.g., IL-1α, IL-1β, IL-6, IL-12, GM-CSF) were markedly elevated in TB-PDM compared to the other groups.

Chemokine Profiles:

• TB-PDM patients had increased levels of CCL2, CCL4, CCL11, CXCL1, CXCL9, CXCL10, and CXCL11 compared to TB or PDM alone. See also: Post-TB DM and Stroke
• TB patients also showed higher levels of these chemokines compared to PDM individuals.

Correlations with Glycemic Measures:

• HbA1c negatively correlated with certain cytokines, such as IL-18 and GM-CSF.
• A positive correlation was observed between HbA1c and the chemokine CCL11. See also: NCD and TB
• Regression analysis identified significant associations between HbA1c, random blood glucose, and several cytokines and chemokines.

Distinct Immune Signature in TB-PDM:

• The findings highlight a unique immune profile in TB-PDM characterized by higher levels of inflammatory and anti-inflammatory markers compared to TB or PDM alone.[1] See also: Prediabetes and TB

Increased MDR-TB Risk in TB-DM Patients: Diabetes mellitus significantly increases the risk of multidrug-resistant tuberculosis (MDR-TB) due to impaired immune function, altered microbial genomics, uncontrolled glucose levels, compromised phagocytic activity, and drug disposition issues. Non-adherence to treatment further exacerbates this risk, leading to higher treatment failure rates compared to TB patients without DM.[2] See also: CV mortality on TB patients

References:

1. Rajamanickam, A., Kothandaraman, S. P., Kumar, N. P., Viswanathan, V., Shanmugam, S., Hissar, S., Nott, S., Kornfeld, H., & Babu, S. (2024). Cytokine and chemokine profiles in pulmonary tuberculosis with pre-diabetes. Frontiers in Immunology, 15, 1447161.

2. Rehman Au, Khattak M, Mushtaq U, Latif M, Ahmad I, Rasool MF, Shakeel S, Hayat K, Hussain R, Alhazmi GA, Alshomrani AO, Alalawi MI, Alghamdi S, Imam MT, Almarzoky Abuhussain SS, Khayyat SM and Haseeb A (2023) The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis. Front. Public Health 11:1244450.

3. Ssekamatte P, Sande OJ, van Crevel R and Biraro IA (2023). Immunologic, metabolic and genetic impact of diabetes on tuberculosis susceptibility. Front. Immunol. 14:1122255.