Insulin resistance, and not β-cell impairment, mediates association betweenMycobacterium tuberculosissensitization and type II diabetes mellitus among US adults

Abstract

SummaryType 2 diabetes mellitus (T2DM) may be a long-term sequela of infection withMycobacterium tuberculosis (M.tb)by mechanisms that remain to be fully explained. We evaluated association betweenM.tbsensitization 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); whileM.tbsensitization status was ascertained by tuberculin skin testing (TST). Exposure toM.tbwas 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 ContextWhat is already known about this subject?Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure toMycobacterium tuberculosis(M.tb) via mechanisms that remain to be unraveledWhat is the key question?To what extent do insulin resistance and β-cell failure mediate the association betweenM.tbsensitization with T2DM among US adults?What are the new findings?M.tbsensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG)Insulin resistance, and not β-cell impairment, likely independently mediate the observed diabetogenic effects ofM.tbsensitizationHow might this impact on clinical and/or public health practice in the foreseeable future?If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM