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A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 μg/L and 0.0786 μg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-β). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20-1.01) μg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), -6.59% (-10.72%, -2.28%), and 1.10% (-2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The adverse health effects of pyrethroids exposure have attracted wide concern. We aimed to assess the associations of bifenthrin, a widely used pyrethroid, with glucose homeostasis and risk of type 2 diabetes mellitus (T2DM) and to explore the underlying mechanism. Serum bifenthrin, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma protein carbonyl (PCO) were determined among 3822 participants from the Wuhan-Zhuhai cohort. Glucose homeostasis was evaluated by FPG, FPI, homeostasis model assessment of insulin resistance (HOMA-IR), impaired fasting glucose (IFG), and abnormal glucose regulation (AGR). The associations of serum bifenthrin with glucose homeostasis and risk of T2DM were assessed by generalized linear models and logistic regression models. The role of PCO in the above associations was evaluated by mediation analyses. After adjusting for covariates, each 2-fold increase in serum bifenthrin was associated with a 0.21 mmol/L increase in FPG and a 5.19%, 10.49%, and 12.18% increase in FPI, HOMA-IR, and PCO levels, respectively. Monotonically elevated ORs of IFG and AGR (all P and P for trend <0.05), but not T2DM (P > 0.05) were detected to be associated with increased bifenthrin. Compared with the participants with low bifenthrin and low PCO, participants with high bifenthrin exposure and high PCO showed a 0.40 mmol/L, 11.07%, and 22.50% increase in FPG, FPI, and HOMA-IR, as well as a 119.97% and 48.88% increase in risks of IFG and AGR, respectively (P for trend <0.05). Moreover, PCO mediated 13.61%-24.98% of the serum bifenthrin-associated glucose dyshomeostasis. The study suggested that bifenthrin exposure was dose-dependently associated with glucose dyshomeostasis in the general Chinese urban adults, and these associations were exacerbated and partly mediated by PCO. Given that other pollutants were not included in this study, the effect of co-exposure of pyrethroids with multiple pollutants is necessary to be considered in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2'-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Polychlorinated biphenyls (PCBs) exposure has been related to the abnormal glucose metabolism and the risk of diabetes. However, the joint effects of various PCBs are uncertain and the potential mechanisms remain unclear. Our objectives were to evaluate the associations of serum PCBs with fasting plasma glucose (FPG) and the risk of diabetes among a general Chinese population, and to estimate the mediating effects of oxidative stress in the above associations. Serum levels of seven indicator-PCBs (PCB-28, 52, 101, 118, 138, 153, and 180) and FPG values were determined among 4498 subjects from the Wuhan-Zhuhai cohort. Oxidative DNA damage biomarker (urinary 8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid peroxidation biomarker (urinary 8-isoprostane, 8-iso-PGF 2α ) were also measured. Positive relationships of serum PCBs with FPG values as well as the risk of diabetes were observed. With each 1% increment in the natural log-transformed values of wet weight serum PCBs, FPG levels increased a 0.125% for PCB-52, 0.168% for PCB-118, 0.221% for PCB-138, 0.273% for PCB-153, and 0.379% for ΣPCB (the sum of seven PCBs). The adjusted odds ratios of diabetes associated with wet weight PCBs were 1.186 for PCB-52, 1.373 for PCB-118, 1.635 for PCB-153, and 1.456 for ΣPCB. The seven serum PCBs showed positive overall effect on the risk of diabetes. Elevated PCB-28, PCB-52, PCB-118, PCB-138, PCB-153, and ΣPCB were associated with the increased urinary 8-iso-PGF 2α , which was positively related with FPG values. Furthermore, urinary 8-iso-PGF 2α partially mediated the positive associations between PCBs and FPG values, with the mediated proportions ranged from 3.20 to 12.93%. In conclusion, our results suggested that serum PCBs were positively related with increased oxidative stress, FPG values, and the risk of diabetes among a general Chinese population. Serum PCBs mixture had positive overall effect on the risk of diabetes. Lipid peroxidation partly mediated the FPG elevation induced by PCB exposure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)