Lian Siyu, Zhang Tingting, Yu Yanchao, Zhang Bao
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China.
Biol Trace Elem Res. 2021 Dec;199(12):4396-4409. doi: 10.1007/s12011-020-02566-1. Epub 2021 Jan 8.
Gestational diabetes mellitus (GDM) represents the frequently occurring medical disorder beginning in the process of pregnancy. No consensus has been reached about the relationship of circulating copper content with the risk of GDM. Therefore, the present work carried out a meta-analysis for summarizing epidemiological research regarding the copper level with the GDM risk. Furthermore, studies using categories of copper concentration as exposure were combined by dose-response meta-analysis.
Related studies were retrieved against the PubMed, Web of Science, and Scopus databases from inception till August 2020. The overall effects were expressed as standard mean difference (SMD). A dose-response meta-analysis was conducted to assess whether the higher copper concentration was associated with higher risks of GDM. Stata 16.0 and Review Manager 5.3 were utilized for data analysis.
A total of fourteen articles involving were retrieved for meta-analysis; in the meantime, 2670 pregnant subjects including 910 GDM cases were enrolled for quantitative analysis. Based on the integrated findings, GDM cases showed increased circulating copper contents relative to those in normal pregnant subjects (SMD = 0.65, 95% CI 0.19 to 1.11; P = 0.005). There was no obvious evidence of publication bias among the studies enrolled. Subgroup analysis showed that such trend was consistent in the third trimester (SMD = 1.21, 95% CI 0.35 to 2.08; P = 0.006) but not second trimester. Meanwhile, circulating copper concentration was significantly higher in women with GDM than those without GDM within the Asian population but not within the Caucasian population (Asia: SMD = 0.73; 95% CI 0.12 to 1.34, P = 0.02; Europe: SMD = 0.49; 95% CI: - 0.23 to 1.20, P = 0.18). Further, serum copper analysis together with subgroup analysis was conducted, and the same result was obtained. For dose-response analysis, the linear associations between circulating copper and risks of GDM were revealed, that higher circulating copper concentration during pregnancy is closely associated with GDM.
According to existing evidence, the serum copper concentration increased among GDM cases compared with subjects with normality in glucose tolerance pregnant subject, in particular among the Asians and during the third trimester. The finding from dose-response analysis suggested that increased copper level is associated with an increased risk of GDM. Nonetheless, more specially designed prospective articles should be carried out for understanding the dynamic relationship of copper concentration with the GDM risk.
妊娠期糖尿病（GDM）是妊娠过程中常见的医学病症。关于循环铜含量与GDM风险之间的关系尚未达成共识。因此，本研究进行了一项荟萃分析，以总结关于铜水平与GDM风险的流行病学研究。此外，使用铜浓度类别作为暴露因素的研究通过剂量反应荟萃分析进行合并。
从创刊至2020年8月，在PubMed、Web of Science和Scopus数据库中检索相关研究。总体效应以标准均数差（SMD）表示。进行剂量反应荟萃分析，以评估较高的铜浓度是否与较高的GDM风险相关。使用Stata 16.0和Review Manager 5.3进行数据分析。
共检索到14篇文章用于荟萃分析；同时，纳入2670名孕妇进行定量分析，其中包括910例GDM病例。综合研究结果显示，与正常孕妇相比，GDM病例的循环铜含量增加（SMD = 0.65，95%CI 0.19至1.11；P = 0.005）。纳入的研究中没有明显的发表偏倚证据。亚组分析显示，这种趋势在妊娠晚期是一致的（SMD = 1.21，95%CI 0.35至2.08；P = 0.006），但在妊娠中期不一致。同时，亚洲人群中GDM女性的循环铜浓度显著高于非GDM女性，而在白种人群中并非如此（亚洲：SMD = 0.73；95%CI 0.12至1.34，P = 0.02；欧洲：SMD = 0.49；95%CI：-0.23至1.20，P = 0.18）。此外进行了血清铜分析和亚组分析，得到了相同的结果。对于剂量反应分析，揭示了循环铜与GDM风险之间的线性关联，即孕期循环铜浓度较高与GDM密切相关。
根据现有证据，与糖耐量正常的孕妇相比，GDM病例的血清铜浓度升高，尤其是在亚洲人群和妊娠晚期。剂量反应分析的结果表明，铜水平升高与GDM风险增加有关。尽管如此，仍需要开展更多专门设计的前瞻性研究，以了解铜浓度与GDM风险之间的动态关系。
