Abstract
BACKGROUND: Extrapulmonary tuberculosis (EPTB) complicates pulmonary tuberculosis (PTB) management. Diabetes mellitus impairs immune function, worsening tuberculosis (TB) outcomes. METHODS: This retrospective study investigates the effect of glycemic control on immune function and TB dissemination in 1,768 TB patients (2022-2024). Patients were stratified by glycated hemoglobin (HbA1c) levels (≤ 6% vs. > 6%) and fasting blood glucose (FBG) concentrations (< 7 vs. ≥ 7 mmol/L). Lymphocyte subsets (CD3(+), CD4(+), CD8(+) T cells, CD19(+) B cells, and CD16(+)CD56(+) natural killer cells) were compared between glycemic control and TB groups. Multiple regression and threshold effect analysis were conducted to assess the effects of HbA1c and CD3(+) T cells on TB dissemination and their critical values. RESULTS: Poor glycemic control was associated with lower cell counts of all lymphocyte subsets in patients with PTB (all p < 0.0001). Similar reductions were observed in patients with concurrent PTB and EPTB (PTB + EPTB) when HbA1c values > 6% (all p < 0.05). When HbA1c values ≤ 6% or FBG concentrations < 7 mmol/L, patients with PTB + EPTB showed lower immune cell counts than PTB (p < 0.05). Multiple regression indicated HbA1c increased TB dissemination risk (OR = 10.95), while CD3(+) T cells showed protective effects. Threshold effect analysis identified an HbA1c values ≥ 7.4% for metabolic control and CD3(+) T cell thresholds of 387/µL (immune deficiency) and 2,100/µL (immune overactivation). CONCLUSIONS: Poor glycemic control impairs immune cells, while EPTB further reduces immune cell numbers. Integrated glycemic management and immunological monitoring help optimize treatment strategies and improve clinical outcomes, particularly in patients at risk for EPTB.