Immunological and Metabolic Associations of Latent Tuberculosis Infection in Type 2 Diabetes Mellitus: A Meta-Analysis of HbA1c Levels and IFN-γ Responses

The intersection of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) represents a major global health challenge. Although T2DM is a recognized risk factor for active TB, its epidemiological impact on latent tuberculosis infection (LTBI) and the underlying immune mechanisms remain unclear. This meta-analysis estimated the global prevalence of LTBI in T2DM, compared LTBI risk with non-diabetic controls, and evaluated the roles of glycated hemoglobin (HbA1c) and interferon-gamma (IFN-γ) in immune dysregulation. HbA1c and IFN-γ were selected because they represent the gold-standard indicators of long-term glycemic control and IGRA-based immune responses, respectively. A systematic search identified observational studies using interferon-gamma release assays (IGRA) to diagnose LTBI in T2DM patients. Random-effects meta-analysis with restricted maximum-likelihood estimation was performed to calculate pooled prevalence, odds ratios (ORs), mean differences (MDs) for HbA1c, and standardized mean differences (SMDs) for IFN-γ levels. Ten studies involving 1,740 T2DM patients and non-diabetic controls were included. The pooled LTBI prevalence in T2DM was 27% (95% CI: 23%–32%; I² = 76%). Compared with non-diabetic individuals, T2DM patients had an 86% higher risk of LTBI (OR 1.86; 95% CI: 1.41–2.45; p<0.0001; I² = 0%). T2DM patients with LTBI also showed poorer glycemic control, with HbA1c levels 0.75% higher than those without LTBI (MD 0.75; 95% CI: 0.51–0.99; p<0.00001; I² = 0%). Furthermore, T2DM was associated with significantly reduced Mycobacterium tuberculosis-specific IFN-γ production (SMD −1.93; 95% CI: −2.69 to −1.16; p<0.00001; I² = 78%). These findings indicate that T2DM substantially increases LTBI risk through hyperglycemia-associated immune dysregulation and impaired Th1-mediated IFN-γ responses. Routine LTBI screening using IGRA and optimal glycemic control should be integrated into diabetes management to reduce progression to active TB.