Wei Zhengxiao, Chen Jinyu, Mei Xue, Yu Yi
Department of Clinical Laboratory, Public Health Clinical Center of Chengdu, Chengdu 610061, China.
Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu 610061, China.
Toxics. 2025 Feb 27;13(3):168. doi: 10.3390/toxics13030168.
Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants associated with various health risks; however, their relationship with all-cause mortality in individuals with diabetes remains unclear. A total of 1256 participants from the National Health and Nutrition Examination Survey (NHANES) were included to explore the association between seven PFAS compounds and all-cause mortality in diabetic patients. Preliminary logistic regression identified three PFAS compounds (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], and 2-(N-methyl-PFOSA) acetate acid [MPAH]) as significantly associated with mortality in the diabetic population. The optimal cut-off values for PFOS, PFOA, and MPAH were determined using the X-tile algorithm, and participants were categorized into high- and low-exposure groups. Kaplan-Meier survival curves and multivariable Cox proportional hazards regression models were used to assess the relationship between PFAS levels and mortality risk. The results showed that high levels of PFOS were significantly associated with increased all-cause mortality risk in diabetic patients (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.06-2.29), while PFOA and MPAH showed no significant associations. To explore mechanisms underlying the PFOS-mortality link, toxicogenomic analysis identified 95 overlapping genes associated with PFOS exposure and diabetes-related mortality using the Comparative Toxicogenomics Database (CTD) and GeneCards. Functional enrichment analysis revealed key biological processes, such as and , with pathways including the , , and . Protein-protein interaction network analysis identified 10 hub genes, and PFOS was found to upregulate or downregulate their mRNA expression, protein activity, or protein expression, with notable effects on mRNA levels. These findings suggest that PFOS exposure contributes to increased mortality risk in diabetic patients through pathways related to glucose metabolism, apoptosis, and cellular signaling. Our study provides new insights into the association between PFAS and all-cause mortality in diabetes, highlighting the need for large-scale cohort studies and further in vivo and in vitro experiments to validate these findings.
全氟和多氟烷基物质（PFAS）是一类与多种健康风险相关的环境污染物；然而，它们与糖尿病患者全因死亡率之间的关系仍不明确。本研究纳入了来自美国国家健康与营养检查调查（NHANES）的1256名参与者，以探讨7种PFAS化合物与糖尿病患者全因死亡率之间的关联。初步逻辑回归分析确定了3种PFAS化合物（全氟辛酸[PFOA]、全氟辛烷磺酸[PFOS]和2-（N-甲基-全氟辛烷磺酸酰胺）乙酸[MPAH]）与糖尿病患者的死亡率显著相关。使用X-tile算法确定了PFOS、PFOA和MPAH的最佳截断值，并将参与者分为高暴露组和低暴露组。采用Kaplan-Meier生存曲线和多变量Cox比例风险回归模型来评估PFAS水平与死亡风险之间的关系。结果显示，PFOS高水平与糖尿病患者全因死亡风险增加显著相关（风险比[HR]：1.55，95%置信区间[CI]：1.06-2.29），而PFOA和MPAH未显示出显著关联。为了探究PFOS与死亡率之间联系的潜在机制，毒理基因组学分析利用比较毒理基因组学数据库（CTD）和基因卡片（GeneCards）确定了95个与PFOS暴露和糖尿病相关死亡率重叠的基因。功能富集分析揭示了关键的生物学过程，如 和 ，其涉及的通路包括 、 和 。蛋白质-蛋白质相互作用网络分析确定了10个枢纽基因，发现PFOS上调或下调了它们的mRNA表达、蛋白质活性或蛋白质表达，对mRNA水平有显著影响。这些发现表明，PFOS暴露通过与葡萄糖代谢、细胞凋亡和细胞信号传导相关的途径导致糖尿病患者死亡风险增加。我们的研究为PFAS与糖尿病患者全因死亡率之间的关联提供了新的见解，强调需要进行大规模队列研究以及进一步的体内和体外实验来验证这些发现。
