Insulin resistance, and not β-cell impairment, mediates association between Mycobacterium tuberculosis sensitization and type II diabetes mellitus among US adults.

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 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 {beta}-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 {beta}-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. Research in ContextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIAccumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis (M.tb) via mechanisms that remain to be unraveled C_LI What is the key question?O_LITo what extent do insulin resistance and {beta}-cell failure mediate the association between M.tb sensitization with T2DM among US adults? C_LI What are the new findings?O_LIM.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) C_LIO_LIInsulin resistance, and not {beta}-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization C_LI How might this impact on clinical and/or public health practice in the foreseeable future?O_LIIf corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomes C_LIO_LIThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM C_LI