Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated the association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or β-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate β-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted.

The authors have declared no competing interest.

RJW and KAW are funded by the Francis Crick Institute which is supported by Cancer Research UK (FC2112), Medical Research Council (FC2112) and Wellcome (FC2112). RJW also receives support from Wellcome (203135). For the purposes of open access the authors have applied a CC-BY public copyright to any author-accepted manuscript arising from this submission. MJS receives support from the US National Institutes of Health (K24 HL166024). NABN gratefully acknowledges support from the South African Medical Research Council, National Research Foundation, the US National Institutes of Health, Medical Research Council (UK), and the Lily and Ernst Hausmann Trust.

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