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丙烯酰胺暴露与中国城市成年人的氧化 DNA 损伤、脂质过氧化和空腹血糖改变的关联及中介分析。

Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation, and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults.

机构信息

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Diabetes Care. 2020 Jul;43(7):1479-1486. doi: 10.2337/dc19-2603. Epub 2020 Apr 28.

Abstract

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

RESEARCH DESIGN AND METHODS

FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.

RESULTS

We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (ΣUAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively ( and/or trend < 0.05). Each 1% increase in AAMA, GAMA, or ΣUAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively ( and trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and ΣUAAM-associated FPG increases, respectively.

CONCLUSIONS

Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.

摘要

目的

日常食物中的丙烯酰胺暴露引起了全球关注。我们旨在评估内源性丙烯酰胺暴露与氧化 DNA 损伤、脂质过氧化和空腹血糖(FPG)改变之间的暴露反应关系,并探讨氧化 DNA 损伤和脂质过氧化在丙烯酰胺内暴露与 FPG 关联中的中介作用。

研究设计和方法

对来自武汉-珠海队列的 3270 名普通成年人测量了 FPG 和氧化 DNA 损伤(8-羟基脱氧鸟苷[8-OHdG])、脂质过氧化(8-异前列腺素 F2α[8-iso-PGF2α])的尿生物标志物以及丙烯酰胺暴露(N-乙酰-S-[2-氨乙基]-L-半胱氨酸[AAMA],N-乙酰-S-[2-氨甲酰基-2-羟乙基]-L-半胱氨酸[GAMA])。采用线性混合模型评估尿丙烯酰胺代谢物与 8-OHdG、8-iso-PGF2α 和 FPG 的相关性。通过中介分析评估 8-OHdG 和 8-iso-PGF2α 的中介作用。

结果

我们发现,尿丙烯酰胺代谢物与 8-OHdG、8-iso-PGF2α 和 FPG(GAMA 与 FPG 除外)以及 8-iso-PGF2α 与 FPG 之间存在显著的线性正剂量反应关系。AAMA、AAMA+GAMA(ΣUAAM)或 8-iso-PGF2α 的对数转换水平每增加 1 个单位,FPG 分别增加 0.17、0.15 或 0.23mmol/L(和/或趋势<0.05)。AAMA、GAMA 或 ΣUAAM 每增加 1%,8-OHdG 分别增加 0.19%、0.27%或 0.22%,8-iso-PGF2α 分别增加 0.40%、0.48%或 0.44%(和趋势<0.05)。增加的 8-iso-PGF2α 而不是 8-OHdG 显著介导了 AAMA 和 ΣUAAM 与 FPG 升高相关的 64.29%和 76.92%。

结论

一般人群接触丙烯酰胺与 FPG 升高、氧化 DNA 损伤和脂质过氧化有关,而氧化 DNA 损伤和脂质过氧化又部分介导了丙烯酰胺与 FPG 升高的关系。

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