Relationship of Circulating Copper Level with Gestational Diabetes Mellitus: a Meta-Analysis and Systemic Review

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.