The cause-effect relation of TB on incidence of DM [TB0121]

1. TB and Blood Glucose Regulation

• Impaired blood glucose tolerance can be normalized after the successful treatment of tuberculosis (TB), but it likely persists as a risk factor for developing type 2 diabetes mellitus (T2DM) in the future.
• The incidence of hyperglycemia in TB patients is attributed to stress, prolonged inflammation, changes in glucose and lipid metabolism, and insulin resistance (IR) syndrome.
• Active TB induces various immunometabolic changes, including increased inflammation, adipose tissue modulation, and elevated free fatty acid levels, leading to IR and potentially T2DM if not clinically managed.
• The prevalence of hyperglycemia in TB patients varies between 10% and 26%, depending on factors such as age, sex, and fasting blood glucose levels.

2. Lipid Metabolism and Insulin Resistance

• TB infection causes dysregulation of lipid metabolism, increasing circulating free fatty acid levels. This leads to ectopic lipid deposition in organs critical for glucose homeostasis, such as the liver and skeletal muscles, resulting in IR development.
• Altered lipid metabolism during TB includes:
  • High low-density lipoprotein (LDL) cholesterol.
  • Low high-density lipoprotein (HDL) cholesterol.
  • High very low-density lipoprotein (VLDL) triglycerides.
• Irregular lipolysis and altered lipid and glucose metabolism in adipose tissue and other organs, including the lungs, occur due to increased intracellular lipid accumulation and inflammatory milieu.

3. TB-DM/IR Co-occurrence and Impact on TB Treatment

• TB-DM co-occurrence may adversely affect TB treatment, increasing the incidence of multi-drug resistance (MDR).
• Dysregulated metabolic pathways and immune system alterations exacerbate clinical manifestations and disease outcomes in co-morbid TB-DM cases.

4. Immune Mechanisms in TB and DM

• In diabetic patients, several immune defects increase susceptibility to TB, including:
  • Impaired bacterial recognition.
  • Reduced phagocytic activity and slower migration rates of macrophages and antigen-presenting cells.
  • Altered secretion of chemokines/cytokines.
  • Impaired T-cell responses.
• These immune impairments compromise the ability to control Mycobacterium tuberculosis (Mtb), increasing Mtb load and disease pathogenicity in organs such as the lungs and liver.
• Diabetic patients with latent TB infection (LTBI) exhibit heightened inflammatory responses, indicating that diabetes influences immune signaling to mycobacterial antigens.

5. Clinical Significance

• The interaction between TB and DM/IR necessitates clinical management to prevent progression to T2DM and mitigate adverse outcomes of TB treatment.
• Understanding the metabolic and immunological interplay is critical for addressing the dual burden of TB-DM in affected populations.

Source: Bisht MK, Dahiya P, Ghosh S and Mukhopadhyay S (2023) The cause-effect relation of tuberculosis on incidence of diabetes mellitus. Front. Cell. Infect. Microbiol. 13:1134036. doi: 10.3389/fcimb.2023.1134036