全氟化合物异构体及替代品与空腹血糖的相关性研究

Associations between isomers and alternatives of per-and polyfluoroalkyl substances and fasting blood glucose

[背景]已有研究表明全氟化合物(PFAS)异构体及替代品可能干扰糖代谢,但目前关于PFAS异构体及替代品与空腹血糖浓度关联的流行病学研究结果尚不一致。缺乏混合污染物对空腹血糖水平的联合效应及关键组分的探索。[目的]探索血糖正常人群中PFAS异构体及替代品与空腹血糖浓度的关联及联合效应,并识别其中的关键组分。[方法]研究基于中国C8异构体健康计划(2015—2016),选取具有完整数据及血糖水平正常的923名成人作为研究对象。分别采用超高效液相色谱串联质谱法及全自动生化仪检测血清中PFAS异构体及替代品及空腹血糖浓度。采用多重线性回归探索16种检出率高于80%的PFAS异构体及替代品与空腹血糖水平的关联。同时采用qgcomp方法、贝叶斯机器核回归(BKMR)模型探索PFAS异构体及替代品混合物对结局指标的联合效应,并判断关键组分。[结果]923名研究对象平均年龄为(62.4±13.8)岁,其中男女分别为472名(51.1%)和451名(48.9%)。PFAS异构体及替代品中全氟-3-甲基-庚烷磺酸(3m-PFOS)、全氟-4-甲基-庚烷磺酸(4m-PFOS)、全氟-5-甲基-庚烷磺酸(5m-PFOS)之和(Σ3+4+5m-PFOS)中位浓度最高为10.20 ng·mL^(–1),直链全氟辛烷磺酸(n-PFOS,9.61 ng·mL^(–1))、全氟辛酸(PFOA,4.55 ng·mL^(–1))、直链全氟己烷磺酸(n-PFHxS,2.48 ng·mL^(–1))、6:2氯化多氟醚磺酸(6:2 Cl-PFESA,1.90 ng·mL^(–1))、全氟-6-甲基-庚烷磺酸(iso-PFOS,1.85 ng·mL^(–1))、全氟正丁酸(PFBA,1.81 ng·mL^(–1))、全氟代正壬酸(PFNA,1.39 ng·mL^(–1))及全氟-1-甲基-庚烷磺酸(1m-PFOS,1.27 ng·mL^(–1))浓度都在1.00 ng·mL^(–1)以上。在调整混杂因素后,PFAS异构体及替代品与空腹血糖浓度正相关。如:随着6:2 Cl-PFESA、PFNA每增加1 ln单位,空腹血糖浓度分别增加0.18(95%CI:0.13~0.23)mmol·L^(–1)、0.24(95%CI:0.18~0.30)mmol·L^(–1)。多污染物模型结果发现PFAS异构体及替代品混合物对空腹血糖浓度存在联合效应。在BKMR模型结果中,相对于混合污染物第50百分位浓度,混合污染物处于第75百分位浓度时空腹血糖浓度增加0.25(95%CI:0.21~0.30)mmol·L^(–1),且PFNA后验纳入概率为0.92,提示PFNA为联合效应中关键组分。[结论]PFAS异构体及替代品与空腹血糖浓度存在正相关及联合效应,PFNA为联合效应的关键组分。

[Background]Previous research indicated that isomers and alternatives of per-and polyfluoroalkyl substances(PFAS)probably disturb glucose metabolism;however,current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent.Besides,studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce.[Objective]To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects,as well as identify the key component among population without glucose metabolism problems.[Methods]We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China(2015—2016).Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS)and automatic biochemical analyzer.We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80%participants with fasting blood glucose.Meanwhile,we utilized qgcomp and Bayesian kernel machine regression(BKMR)models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component.[Results]The average age among the 923 participants in this study was(62.4±13.8)years old,including 472 men(51.1%)and 451 women(48.9%).Among selected PFAS isomers and alternatives,the highest serum concentration wasΣ3+4+5m-PFOS(perfluoro-3/4/5-methylheptanesulfonate)with a median concentration of 10.20 ng·mL^(−1).The concentrations of linear perfluorooctane sulfonate(n-PFOS,9.61 ng·mL^(−1)),perfluorooctanoic acid(PFOA,4.55 ng·mL^(−1)),linear perfluorohexane sulfonic acid(n-PFHxS,2.48 ng·mL^(−1)),6:2 chlorinated polyfluorinated ethersulfonic acid(6:2 Cl-PFESA,1.90 ng·mL^(−1)),perfluoro-6-methylheptanesulfonate(iso-PFOS,1.85 ng·mL^(−1)),perfluorobutanoic acid(PFBA,1.81 ng·mL^(−1)),perfluorinated n-nonanoic acid(PFNA,1.39 ng·mL^(−1)),and perfluoro-1-methylheptanesulfonate(1m-PFOS,1.27 ng·mL^(−1))were higher than 1.00 ng·mL^(−1).After being adjusted for selected confounders,PFAS isomers and alternatives were positively associated with fasting blood glucose.With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA,the estimated changes of fasting blood glucose were 0.18(95%CI:0.13,0.23)mmol·L^(−1) and 0.24(95%CI:0.18,0.30)mmol·L^(−1),respectively.The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose.The BKMR models reveals that as the quantiles of mixture elevated from the 50th to the 75th percentile,the values of fasting blood glucose increased 0.25(95%CI:0.21,0.30)mmol·L^(−1),and the posterior inclusion probability of PFNA was 0.92,implying that PFNA was the key component.[Conclusion]PFAS isomers and alternatives are positively associated with fasting blood glucose.PFNA is the key component of the joint association.