Research progress on the association and mechanisms between emerging contaminants exposure and the risk of gestational diabetes mellitus
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摘要: 妊娠期糖尿病(gestational diabetes mellitus, GDM)是一种常见的妊娠并发症, 与不良妊娠结局密切相关, 且发病率正逐年上升。动物实验和流行病学研究提示, 孕期新污染物暴露与GDM的发生关联密切, 但二者之间的致病机制尚未阐明, 是当前的研究热点。与GDM有关的新污染物包括全氟与多氟烷基化合物、双酚类化合物、邻苯二甲酸酯、多氯联苯、有机氯农药和烷基酚类化合物等。对上述几类代表性新污染物与GDM发病风险之间的流行病学证据及可能的作用机制进行综述, 以期为进一步的机制研究和GDM防治提供思路。Abstract: Gestational diabetes mellitus (GDM) is a common medical complication of pregnancy, closely associated with adverse pregnancy outcomes, and its incidence is increasing rapidly. Animal experiments and epidemiological studies suggest a strong association between exposure to emerging contaminants during pregnancy and the occurrence of GDM. However, the pathogenic mechanisms linking emerging contaminants to GDM remain unclear, making this a prominent topic in current research. Emerging contaminants associated with GDM include per- and polyfluoroalkyl substances, bisphenols, phthalates, polychlorinated biphenyls, organochlorine pesticides, and alkyl phenols. This review summarizes the epidemiological evidence and potential mechanisms underlying the association between these emerging contaminants and GDM, aiming to provide insights for future mechanistic research and the prevention and control of emerging contaminants.
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Key words:
- Emerging contaminants /
- Gestational diabetes mellitus /
- Mechanism
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表 1 探究新污染物与GDM发病风险之间关联的队列研究
Table 1. Cohort Studies investigating the association between emerging pollutants and risk of GDM
第一作者
First author年份
Year国家/地区
Country/
region样本量
Sample
size检测样本
Specimen检测物质
Analyte主要发现
Main findingsMatilla-Santander[11] 2017 西班牙
Spain1 240 孕早期血浆
Plasma in the first trimesterPFOS、PFOA、PFHxS、PFNA PFOS、PFHxS浓度与IGT呈正相关
Positive association between PFOS, PFHxS, and IGTWang[12] 2018 中国
China385 孕早、中、晚期血清
Serum in the first, middle and third trimesters of pregnancyPFOA、PFOS PFOA和PFOS与GDM发生风险无关
No association between PFOA, PFOS, and GDMRahman[13] 2019 美国
United
States2 292 孕期血浆样本
Pregnancy plasma samplePFNA、PFOA、PFHp A、
PFDoDA这4种PFAS同系物在有T2D家族史的妇女中与GDM呈显著正相关
Positive association of these 4 PFAS homologs with GDM in women with a family history of T2DMPreston[14] 2020 美国
United
States1 540 孕早期血浆
Plasma in the first trimester8种PFAS同系物
8 PFAS homologs某些PFAS可能会改变妊娠期的葡萄糖稳态, 但与GDM的发生风险无关
Some PFAS may alter glucose homeostasis during pregnancy but are not associated with the risk of developing GDMYu[15] 2021 中国
China2 747 孕早期血浆
Plasma in the first trimester10种PFAS同系物
10 PFAS homologsPFAS暴露与妊娠期葡萄糖稳态紊乱和GDM风险增加有关
PFAS exposure is associated with impaired glucose homeostasis during pregnancy and an increased risk of GDMShapiro[16] 2015 加拿大
Canada1 274 孕早期尿样
Urine sample during the first trimester总BPA
Total BPABPA水平与IGT或GDM之间的关联没有统计学意义
No association between BPA and IGT or GDMWang[17] 2017 中国
China620 孕晚期尿样
Urine sample in the third trimesterBPA BPA与75 g OGTT中的2-h PG浓度降低有关, 并降低了GDM的风险
BPA is associated with decreased 2-h PG in the 75 g OGTT and a reduced risk of GDMZhang[18] 2019 中国
China1 841 孕早期尿样
Urine sample during the first trimesterBPA、BPS、BPF、BPAF 在正常体重的孕妇中, BPAF与GDM发病风险增加有关
Positive association between BPAF and GDM in normal-weight pregnant womenSoomro[19] 2024 加拿大
Canada420 孕中期尿样
Urine sample from the second trimesterBPA、BPS BPA与GDM发病风险增加有关, 未观察到BPS与GDM之间的关联
Positive association between BPA and GDM risk; no association between BPS and GDMShapiro[16] 2015 加拿大
Canada1 274 孕早期尿样
Urine sample during the first trimester11种PAEs代谢物
11 PAEs metabolitesPAEs代谢物与IGT或GDM之间未观察到有统计学意义的关联
No statistically significant associations between PAEs metabolites and IGT or GDMShaffer[20] 2019 美国
United
States705 孕早、晚期尿样
Urine samples in the first and third trimesters of pregnancy11种PAEs代谢物
11 PAEs metabolites孕早期和孕晚期平均MEP与GDM呈正关联
Positive association between average MEP levels in early and late pregnancy with GDMZukin[21] 2021 美国
United
States415 孕早、中期末尿样
Urine samples from the first and second trimesters of pregnancy11种PAEs代谢物
11 PAEs metabolites未发现任何PAEs代谢物与IGT或GDM之间的关联
No associations between any PAEs metabolites and IGT or GDMSoomro[19] 2024 加拿大
Canada420 孕中期尿样
Urine sample from the second trimester12种PAEs代谢物
12 PAEs metabolites未观察到PAEs代谢物与GDM之间的关联
No associations between PAEs metabolites and GDMJaacks[22] 2016 美国
United
States258 孕前血清
Pre-pregnancy serum36种PCB同系物
36 PCB homologs调整血清总脂质的PCBs同系物与GDM呈负相关联
Negatively associated between lipid-adjusted PCB homologs and GDMShapiro[23] 2016 加拿大
Canada1 274 孕早期血浆
Plasma in the first trimester24种PCB同系物
24 PCB homologs未发现PCBs与GDM或IGT相关的证据
No associations between PCBs and IGT or GDMVafeiadi[24] 2017 希腊
Greece939 孕早期血清
Serum in the first trimester6种PCB同系物
6 PCB homologs孕早期PCBs水平高的妇女发生GDM的风险更高
Positive association between higher PCB levels in early pregnancy and GDMRahman[13] 2019 美国
United
States2 292 孕期血浆
Plasma during pregnancy35种PCB同系物
35 PCB homologs高氯代PCBs、总PCBs以及非二噁英类PCBs与GDM的发生风险呈正相关
Positive association between highly chlorinated PCBs, total PCBs, and non-dioxin-like PCBs and the risk of developing GDMSaunders[25] 2014 法国
France779 孕晚期血浆
Plasma in the third trimester十氯酮
Chlordecone未观察到十氯酮暴露与GDM发病风险之间的显著关联
No significant association between chlordecone and GDMShapiro[23] 2016 加拿大
Canada1 274 孕早期尿样
Urine sample during the first trimester11种有机氯农药
11 organochlorine pesticides未发现有机氯农药与妊娠期GDM或IGT相关的证据
No associations between OCPs metabolites and IGT or GDMVafeiadi[24] 2017 希腊
Greece939 孕早期血清
Serum in the first trimesterHCB、p, p'-DDT、p, p'DDE、BDE-47 产前p, p'-DDE和HCB暴露与GDM无显著关联
No associations between p, p'-DDE, HCB and IGT or GDMPang[26] 2024 中国
China2 035 孕早期血清
Serum in the first trimesterNP、4-N-OP、4-N-NP、4-T-OP 孕早期烷基酚暴露可能对GDM风险具有胎儿性别特异性的潜在影响, 携带女性胎儿的孕妇更易患GDM
Alkylphenol exposure in early pregnancy may have a fetal sex-specific effect on GDM risk, with pregnant women carrying female fetuses being more susceptible to developing GDM注: PFOA, 全氟辛酸; PFOS, 全氟辛烷磺酸; PFNA, 全氟壬酸; PFHxS, 全氟己烷磺酸; PFDA, 全氟癸酸; PFHpA, 全氟庚酸; PFDoDA, 全氟二十二烷酸; PFAS, 全氟与多氟烷基化合物; BPA, 双酚A; BPS, 双酚S; BPF, 双酚F; BPAF, 双酚AF; PAEs, 邻苯二甲酸酯类; MEP, 邻苯二甲酸单乙酯; PCBs, 多氯联苯; HCB, 六氯苯; p, p'-DDT, 对位-对位'-二氯二苯三氯乙烷(滴滴涕); p, p'-DDE, 对位-对位'-二氯二苯乙烯(滴滴伊); BDE-47, 2, 2', 4, 4'-四溴二苯醚; NP, 壬基酚; 4-N-OP, 4-正辛基苯酚; 4-N-NP, 4-正壬基苯酚; 4-T-OP, 4-叔丁基苯酚; IGT, 糖耐量受损; GDM, 妊娠期糖尿病; T2DM, 2型糖尿病; OGTT, 口服葡萄糖耐量测试; 2-h PG, 2 h血浆葡萄糖浓度。
Note: PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFNA, perfluorononanoic acid; PFHxS, perfluorohexane sulfonic acid; PFDA, perfluorodecanoic acid; PFHpA, perfluoroheptanoic acid; PFDoDA, perfluorodocosanoic acid; PFAS, per-and polyfluoroalkyl substances; BPA, bisphenol A; BPS, bisphenol S; BPF, bisphenol F; BPAF, bisphenol AF; PAEs, phthalate esters; MEP, monoethyl phthalate; PCBs, polychlorinated biphenyls; HCB, hexachlorobenzene; p, p'-DDT, p, p'-dichlorodiphenyltrichloroethane (DDT); p, p'-DDE, p, p'-dichlorodiphenylethylene (DDE); BDE-47, 2, 2', 4, 4'-tetrabromodiphenyl ether; NP, nonylphenol; 4-N-OP, 4-n-octylphenol; 4-N-NP, 4-n-nonylphenol; 4-T-OP, 4-tert-octylphenol; IGT, impaired glucose tolerance; GDM, gestational diabetes mellitus; T2DM, type 2 diabetes mellitus; OGTT, oral glucose tolerance test; 2-h PG, 2-hour plasma glucose.
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