Prediabetes is a serious metabolic disorder that is often overlooked and 70% of individuals with prediabetes would eventually develop type 2 diabetes. The diabetogenic effects of pesticides have been reported in toxicological studies but their association with prediabetes is rarely investigated. We aimed to evaluate the association between pesticide exposure and impaired glucose regulation (IGR), including prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and insulin resistance, in a general U.S. non-diabetic population. Three classes of urinary pesticides, including organophosphorus pesticides (OPs), pyrethroid, and herbicides were measured. Generalized linear regression, restricted cubic spline, and Bayesian kernel machine regression (BKMR) models were combined to evaluate their associations. 3,5,6-trichloropyridinol (TCPY) was positively associated with prediabetes and IGT (highest vs lowest TCPY quartile: prediabetes: OR: 1.97, 95% CI: 1.18, 3.31; IGT: OR: 2.03, 95% CI: 1.14, 3.66) in a linear dose-response manner (P for nonlinear<0.05). Another two metabolites of OPs, malathion dicarboxylic acid (MDCA) diacid and para-nitrophenol (PNP), were found to increase the odds ratio of insulin resistance (PNP: OR: 1.22, 95% CI: 1.05, 1.42; MDCA: OR: 1.36, 95% CI: 1.08, 1.70) with linear dose-response curves (P for nonlinear<0.05). Considering mutual exposure to multiple pesticides, TCPY, MDCA, and PNP made the most contributions in the mixture exposure and IGR. No obvious interactions among pesticides were found in the multiple exposure settings. The odds ratio of TCPY exposure and prediabetes was increased with advancing age but not related to body mass index (BMI). The results remained robust in sensitivity analysis with restricted participants without abnormal urinary creatinine and unsteady glucose or insulin levels. Our findings suggested the close relationship between OPs and impaired glucose regulation, especially in older adults, which provides insights into the prevention of diabetes at the earlier stage.

中文翻译：

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美国非糖尿病人群的多种农药暴露和血糖调节受损


糖尿病前期是一种经常被忽视的严重代谢紊乱，70% 的糖尿病前期患者最终会发展为 2 型糖尿病。毒理学研究中报道了农药的致糖尿病作用，但很少研究它们与糖尿病前期的关系。我们旨在评估农药暴露与葡萄糖调节受损 （IGR） 之间的关联，包括糖尿病前期 （定义为空腹血糖受损 [IFG] 和/或葡萄糖耐量受损 [IGT]）和胰岛素抵抗，在一般美国非糖尿病人群中。测量了三类尿液杀虫剂，包括有机磷杀虫剂 （OPs）、拟除虫菊酯和除草剂。将广义线性回归、受限三次样条和贝叶斯核机回归 （BKMR） 模型相结合以评估它们的关联。3,5,6-三氯吡啶醇 （TCPY） 与糖尿病前期和 IGT 呈正相关（最高与最低 TCPY 四分位数：糖尿病前期：OR：1.97,95% CI：1.18,3.31;IGT：OR：2.03,95% CI：1.14,3.66）以线性剂量反应方式 （P 为非线性<0.05）。发现 OPs 的另外两种代谢物马拉硫磷二羧酸 （MDCA） 二酸和对硝基苯酚 （PNP） 增加了胰岛素抵抗的比值比（PNP：OR：1.22,95% CI：1.05,1.42;MDCA：OR：1.36,95% CI：1.08,1.70），线性剂量反应曲线 （P 为非线性<0.05）。考虑到多种农药的相互暴露，TCPY 、 MDCA 和 PNP 在混合物暴露和 IGR 中的贡献最大。在多次曝光设置中未发现农药之间的明显相互作用。TCPY 暴露和糖尿病前期的比值比随着年龄的增长而增加，但与体重指数 （BMI） 无关。 在敏感性分析中，结果仍然稳健，受限参与者没有异常的尿肌酐和不稳定的葡萄糖或胰岛素水平。我们的研究结果表明 OPs 与葡萄糖调节受损之间存在密切关系，尤其是在老年人中，这为早期预防糖尿病提供了见解。