Discordance between measures of Mycobacterium tuberculosis sensitization and type 2 diabetes mellitus in the United States (NHANES): A population-based cohort study

Objective: We examined how latent TB infection (LTBI), evaluated by cell-mediated immune responses to Mycobacterium tuberculosis (Mtb) antigens, impacts glucose metabolism in US adults. Methods: Mtb sensitization was evaluated by interferon-γ (IFN-γ) release assay (IGRA+: assay reactivity) and tuberculin skin testing (TST+: skin induration ≥10 mm), and categorized as: IGRA-/TST- (TB uninfected controls); IGRA-/TST+; IGRA+/TST-; or IGRA+/TST+. Diabetes was ascertained by fasting plasma glucose (FPG) ≥7.0 mmol/L, HbA1c ≥6.5% and/or antidiabetic medication. Adjusted generalized additive models examined nonlinear effects of skin induration and IFN-γ reactivity on FPG and HbA1c; and LTBI on diabetes prevalence. Results: Among 1787 (IGRA-/TST-), 101 (IGRA-/TST+), 92 (IGRA+/TST-), and 99 (IGRA+/TST+) adults, skin induration linearly associated with FPG [effective degrees of freedom (EDF) =1.01; p<0.001] and non-linearly with HbA1c [EDF=1.76; p=0.003]. IFN-γ reactivity correlated with neither FPG [p=0.58] nor HbA1c [p=0.94]. Relatedly, adjusted diabetes prevalence was greater in IGRA-/TST+ [24.9%; p=0.048] and IGRA+/TST+ [27.3%; p=0.004] but not IGRA+/TST- [15.9%; p=0.69] individuals than among controls [15.3%]. Conclusions: LTBI associated with glycemic measures and diabetes when assessed by skin induration, but not IFN-γ release. This suggests an association with innate immune activation rather than acquired T-cell response, as determined by ex vivo IFN-γ release assay.