环境风险评分量化全氟和多氟烷基物质暴露与肥胖相关胰岛素抵抗的关联

Quantifying the association between PFAS exposure and obesity-related insulin resistance using an environmental risk score

摘要

目的 探究5种主要的全氟和多氟烷基物质(per- and polyfluoroalkyl substance, PFAS)暴露与肥胖相关胰岛素抵抗之间的关联。方法 基于美国国家健康与营养调查数据,采用加权广义线性模型和四分位数法分析PFAS与肥胖相关胰岛素抵抗之间的关联;再构建加权分位数和回归模型探讨混合暴露效应及组分贡献;进一步采用自适应弹性网络构建PFAS环境风险评分(PFAS environmental risk score, PFAS-ERS),量化PFAS-ERS与肥胖相关胰岛素抵抗之间的剂量-反应关系。结果 5种PFAS物质中,全氟壬酸与各结局指标均呈正向关联[甘油三酯-葡萄糖-体质量指数(triglyceride-glucose-body mass index, TyG-BMI)β=0.022,95% CI:0.004～0.039;TyG-腰围(WC)β=0.018,95% CI:0.005～0.030;TyG-腰高比(WHtR)β=0.019,95% CI:0.006～0.031]。混合暴露分析显示PFAS混合暴露与各结局指标均呈正向关联,其中全氟辛酸和全氟壬酸贡献最大。PFAS-ERS与所有结局指标均呈正向关联,且第四分位数组关联性最强(TyG β=0.020,95% CI:0.013～0.027;TyG-BMI β=0.086,95% CI:0.060～0.112;TyG-WC β=0.082,95% CI:0.061～0.102;TyG-WHtR β=0.071,95% CI:0.052～0.090)。结论 PFAS(尤其是全氟辛酸和全氟壬酸)暴露与肥胖相关胰岛素抵抗之间存在显著关联。采用结合肥胖参数的TyG复合指标,有助于更全面刻画PFAS与代谢健康的潜在风险。本研究结果可为环境健康风险评估提供重要依据。

Abstract

Objective To investigate the association of exposure to five major per- and polyfluoroalkyl substances (PFAS) with obesity-related insulin resistance. Methods Based on data from the National Health and Nutrition Examination Survey (NHANES), weighted generalized linear models and quartile-based methods were used to assess the associations between individual PFAS and obesity-related insulin resistance. Weighted quantile sum (WQS) regression was applied to examine the effects of mixed exposures and the relative contribution of each component. Additionally, an adaptive elastic-net (AENET) model was used to construct a PFAS environmental risk score (PFAS-ERS) to evaluate dose-response relationships between PFAS-ERS and insulin resistance indicators. Results Among the five PFAS compounds, perfluorononanoic acid was positively associated with all the outcome indicators (TyG-BMI β=0.022, 95% CI: 0.004-0.039; TyG-WC β=0.018, 95% CI:0.005-0.030; TyG-WHtR β=0.019, 95% CI:0.006-0.031). Mixed exposure analysis showed that combined PFAS exposure was positively associated with all insulin resistance indicators, with perfluorooctanoic acid and perfluorononanoic acid contributing most. PFAS-ERS was positively associated with all the outcome indicators, with the strongest associations observed in the highest quartile (TyG β=0.020, 95% CI: 0.013-0.027; TyG-BMI β=0.086, 95% CI:0.060-0.112; TyG-WC β=0.082, 95% CI:0.061-0.102; TyG-WHtR β=0.071, 95% CI:0.052-0.090). Conclusion PFAS exposure (particularly PFOA and PFNA) is significantly associated with insulin resistance indices. The use of TyG composite indicators incorporating obesity parameters may help more comprehensively characterize the potential risks of PFAS exposure to metabolic health. These findings provide important evidence for environmental health risk assessment.

关键词

全氟和多氟烷基物质(PFAS) / TyG-肥胖复合指标 / 加权分位数和回归 / 自适应弹性网络 / 环境风险评分

Key words

per- and polyfluoroalkyl substance (PFAS) / TyG-obesity composite index / weighted quantile sum regression / adaptive elastic-net / environmental risk score

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基金资助

国家自然科学基金资助项目(82103943)