Adults with Mtb infection and pre-DM have increased levels of IGR [TB0102]

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Immunopathy associated with diabetes or pre-diabetes is characterized, in part, by chronic inflammation driven by persistent hyperglycemia, resulting in several complications. Generally, data from clinical tuberculosis (TB) studies indicate that patients with diabetes demonstrate a robust TB antigen-specific immune response. However, diabetes is paradoxically associated with worse TB clinical outcomes, including delayed culture conversion, increased risk of mortality, and higher rates of TB relapse.

Although diabetes is an established risk factor for TB disease, additional information to identify individuals with diabetes and latent TB infection (LTBI) at greatest risk of progression to TB disease is urgently needed. Previous studies among children, adolescents, and adults who converted from a negative to a positive LTBI test reported that increased quantitative QuantiFERON-TB Gold (QFT) interferon-gamma (IFN-γ) values were predictive of progression to TB disease.

Participants who self-reported a previous diabetes diagnosis by a healthcare professional were defined as having diabetes regardless of HbA1c results. In the absence of self-reported diabetes, participants were classified by HbA1c as euglycemic (≤5.6%), pre-diabetes (5.7–6.4%), or diabetes (≥6.5%). Among participants with diabetes, additional analyses were conducted with diabetes further classified as poorly controlled (HbA1c ≥7%) or controlled (HbA1c <7%), and based on whether it was a previously known diagnosis (e.g., self-reported by the participant) or a new diagnosis (no self-reported diabetes diagnosis and HbA1c ≥6.5%).

One in five participants with diabetes or pre-diabetes had a high IFN-γ TB antigen response measured by QFT, which is more than 1.5 times the proportion among euglycemic participants. After adjusting for likely confounding factors, we found that participants with pre-diabetes had almost double the odds of a high IFN-γ TB antigen response compared to euglycemic participants. Importantly, we observed the greatest proportion of high IFN-γ TB antigen responses, nearly one-third, among participants with poorly controlled diabetes.

Furthermore, the relationship between diabetes status and high IFN-γ TB antigen response may vary by place of birth (U.S.-born vs. foreign-born) and tuberculin skin test (TST) status. Overall, these findings suggest that, in the context of diabetes and pre-diabetes, the TB antigen response to Mycobacterium tuberculosis (Mtb) infection may be similar to IFN-γ responses among patients with TB disease and concurrent diabetes, wherein antigen-specific immune responses are exaggerated compared to euglycemic patients. In the context of TB disease, diabetes and pre-diabetes are associated with an increased pro-inflammatory cytokine response typically associated with successful host defense against TB.

Source: Magee, M.J., Trost, S.L., Salindri, A.D., Amere, G., Day, C.L. and Gandhi, N.R., 2020. Adults with Mycobacterium tuberculosis infection and pre-diabetes have increased levels of QuantiFERON interferon-gamma responses. Tuberculosis, 122, p.101935.

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