Li Xinping, Huang Yichao, Xing Yuling, Hu Chen, Zhang Wenxin, Tang Yi, Su Weijie, Huo Xia, Zhou Aifen, Xia Wei, Xu Shunqing, Chen Da, Li Yuanyuan
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong, People's Republic of China.
Environ Int. 2020 Apr;137:105527. doi: 10.1016/j.envint.2020.105527. Epub 2020 Jan 31.
Previous studies have observed that cadmium (Cd) exposure of pregnant women was associated with increased risk of gestational diabetes mellitus (GDM). However, the potential mechanism still remains unclear. In addition, various animal studies have suggested that Cd exposure could affect fatty acids (FAs) metabolism, but data on humans are scant.
We conducted a nested case-control study to investigate the associations of urinary Cd concentrations with levels of circulating FAs and risk of GDM in pregnant women, and further to examine the role of FAs in mediating the relationship between Cd exposure and risk of GDM.
A total of 305 GDM cases were matched to 305 controls on pregnant women's age (±2 years) and infant's gender from a birth cohort study conducted in Wuhan, China. Urinary Cd concentrations and levels of plasma FAs between 10 and 16 gestational weeks were measured using inductively coupled plasma mass spectrometry and gas chromatography-mass spectrometry, respectively. Conditional logistic regressions models were used to estimate the associations of Cd concentrations and levels of FAs with the risk of GDM. Multiple linear regression models were applied to estimate the associations between Cd concentrations and levels of FAs. Mediation analysis was used to assess the mediating role of FAs in the association of Cd with the risk of GDM.
Urinary concentrations of Cd in cases (median: 0.69 μg/L) were significantly higher than controls (median: 0.59 μg/L, P < 0.05). Cd concentrations were positively associated with the risk of GDM (P = 0.003). Compared to the first tertile of Cd, the adjusted odds ratios (95% confidence intervals) of GDM risk were 2.08 (1.29, 3.36) for the second tertile and 2.09 (1.32, 3.33) for the third tertile. Cd concentrations were positively correlated with levels of eicosadienoic acid and arachidonic acid/eicosapentaenoic acid ratio, but negatively correlated with levels of stearic acid, eicosapentaenoic acid, total odd-chain saturated fatty acids, total n-3 polyunsaturated fatty acids (PUFAs), and n-3 PUFAs/n-6 PUFAs ratio. We did not observe evidence that the association of Cd exposure and risk of GDM was mediated through FAs.
Our findings confirmed the association of higher Cd exposure with increased risk of GDM in pregnant women, and provided forceful epidemiological evidence for the relation of Cd concentrations and levels of FAs.
既往研究观察到孕妇镉(Cd)暴露与妊娠期糖尿病(GDM)风险增加有关。然而,潜在机制仍不清楚。此外,各种动物研究表明,镉暴露可能影响脂肪酸(FAs)代谢,但关于人类的数据很少。
我们进行了一项巢式病例对照研究,以调查孕妇尿镉浓度与循环脂肪酸水平及GDM风险之间的关联,并进一步探讨脂肪酸在介导镉暴露与GDM风险关系中的作用。
从中国武汉开展的一项出生队列研究中,按照孕妇年龄(±2岁)和婴儿性别,将305例GDM病例与305例对照进行匹配。分别采用电感耦合等离子体质谱法和气相色谱 - 质谱法测量孕10至16周时的尿镉浓度和血浆脂肪酸水平。使用条件逻辑回归模型估计镉浓度和脂肪酸水平与GDM风险的关联。应用多元线性回归模型估计镉浓度与脂肪酸水平之间的关联。采用中介分析评估脂肪酸在镉与GDM风险关联中的中介作用。
病例组尿镉浓度中位数为0.69μg/L,显著高于对照组(中位数为0.59μg/L,P<0.05)。镉浓度与GDM风险呈正相关(P = 0.003)。与镉的第一个三分位数相比,GDM风险的校正比值比(95%置信区间)在第二个三分位数为2.08(1.29,3.36),在第三个三分位数为2.09(1.32,3.33)。镉浓度与二十碳二烯酸水平和花生四烯酸/二十碳五烯酸比值呈正相关,但与硬脂酸、二十碳五烯酸、总奇数链饱和脂肪酸、总n-3多不饱和脂肪酸(PUFAs)以及n-3 PUFAs/n-6 PUFAs比值呈负相关。我们没有观察到证据表明镉暴露与GDM风险的关联是通过脂肪酸介导的。
我们的研究结果证实了孕妇镉暴露水平较高与GDM风险增加之间的关联,并为镉浓度与脂肪酸水平的关系提供了有力的流行病学证据。