Benzene Exposure in Relation to the Development of Glycemic Dysregulation and Type 2 Diabetes Mediated by Oxidative Stress and Aggravated by Inflammation in A Repeated-Measure Prospective Cohort Study of Chinese Adults

Aims Whether and how benzene (a ubiquitous environmental pollutant posing substantial public health concerns) exposure contributes to glycemic dyshomeostasis and type 2 diabetes (T2DM) remain unclear. Methods Among 3422 Chinese adults from the Wuhan-Zhuhai cohort, urinary N-Acetyl-S-(phenyl)-L-cysteine (PMA; dependable benzene exposure biomarker) was repeatedly measured at baseline and 3-year follow-up to investigate its associations with glycemic homeostasis markers (fasting plasma glucose [FPG] and insulin [FPI], homeostasis model assessment of insulin resistance [HOMA-IR], insulin resistance [IR], and impaired fasting glucose [IFG]) and T2DM appropriately by performing general linear, logistic, and Poisson regression models. Oxidative stress (exhaled carbon monoxide [eCO]; urinary 8-hydroxy-2’-deoxyguanosine and 8-iso-prostaglandin-F2α; plasma protein carbonyl) and inflammation (plasma C-reactive protein [CRP]; mean platelet volume [MPV]; neutrophil-to-lymphocyte ratio [NLR]) biomarkers were detected to explore their roles by performing mediation and interaction analyses. Results Cross-sectionally, positive PMA-FPG (β=0.014, 95% confidence interval: 0.005∼0.024), PMA-FPI (0.076, 0.049∼0.104), PMA-HOMA-IR (0.090, 0.059∼0.122), PMA-IR (odds ratio=1.516, 1.192∼1.929), PMA-IFG (1.653, 1.164∼2.343), and PMA-T2DM (1.445, 1.019∼2.045) associations were discovered. Longitudinally, positive PMA-FPG (β=0.059, 0.016∼0.101) and PMA-HOMA-IR (quartile 4 vs. 1: 0.054, 0.002∼0.106; P trend =0.041) associations were uncovered, and participants with consistently high PMA level had higher risks of incident IR (risk ratio=2.513, 1.638∼3.857) and T2DM (2.834, 1.042∼7.708). PMA-CRP and PMA-MPV interactions on FPG, PMA-CRP interaction on IFG, and PMA-NLR interaction on T2DM were detected. 8-hydroxy-2’-deoxyguanosine and eCO mediated 4.74% and 5.97% of the PMA-FPI and PMA-T2DM associations, respectively. Conclusions Benzene exposure of general adults was linked to the development of glycemic dyshomeostasis and T2DM possibly through mediation by oxidative stress and interaction with inflammation.