The present study showed pregnant women who had excessive or inadequate weight gain were more likely to develop diabetes than women who had normal weight gain. Also, excessive weight gains in obese women and inadequate weight gain in underweight women are associated with gestational diabetes. In parallel with our study, Gibson et al. reported that weight gain during pregnancy in obese and overweight women was associated with gestational diabetes mellitus [40]. In a cohort study, increased BMI classification from normal to overweight or overweight to obesity was associated with the increased risk of GDM [41]. However, in several studies, there was no association between "excessive mid-trimester weight gain" and abnormal glucose tolerance test results [42, 43]. According to a meta-analysis study, excessive gestational weight gain does not affect the risk of gestational diabetes in normal weight and overweight/obese women [44]. Gestational weight gain early in pregnancy is often related to increased plasma volume; However, the increase in adipose tissue starts from 12 to 14 weeks of gestation in overweight and obese women and potentially earlier in underweight and normal-weight women [45]. Gestational weight gain has also been shown to be inversely proportional to insulin sensitivity changes [46]. Gestational diabetes develops when pancreatic β cell function cannot adequately maintain normoglycemia due to increased insulin resistance. Since overweight and obese women have increased insulin resistance before conception; therefore, excessive weight gain may "push them over the edge" toward GDM development [40].
So far, limited studies have examined the relationship between Cu and GDM risk. This study found that the frequency of pregnant women with high serum Cu concentration in the GDM group was higher than the control group. Also, plasma Cu concentrations were not significantly associated with GDM risk. In the previous case-control studies conducted by Wang et al. and Li et al., Cu concentrations in the GDM group were higher than the control group, consistent with our results. [20, 47]. However, in a study, no difference was observed in Cu concentrations in women with gestational diabetes than in healthy pregnant women [48]. Recently, a meta-analysis including 910 GDM and 1760 healthy pregnant women discovered that in the Asian people during the third trimester, Cu concentrations in women with GDM were higher than the control group. Nonetheless, in the Caucasian people, no significant difference was between the two groups [49]. Therefore, this inconsistency of results could be related to different ethnicity, geographical locations, sample size, and confounding factors. Cu may be involved in glucose metabolic disorders' pathogenesis through reactive oxygen species (ROS) production. ROS is thought to be involved in the development of insulin resistance. Cu ions can facilitate ROS production by mediating the transfer of electrons[50]. Cu can increase the production rate of advanced glycation end products (AGEs) associated with diabetes and its complications[51]. Cu ions can stimulate the accumulation of human Amylin peptide in amyloid fibrils associated with decreased β cell mass and progressive β cell failure[52, 53]. Also, the production of H2O2 byproducts can induce oxidative damage, cytotoxicity, and the progressive destruction of β cells[54].
In our study, normal serum Zn concentration was inversely associated with the cause of GDM. Also, the frequency of pregnant women with high serum Zn concentration in the GDM group was higher than the control group. In parallel with our study Zhou et al. [55] found Zn increases OGTT. However, Behboudi-Gandevani et al. [56] did not find any differences in Zn serum concentration between GDM and non-GDM groups. Unlike our findings, in Wang et al. study [47], serum Zn concentrations in the GDM group were lower than the healthy group. Another study mentioned that Zn supplementation increased insulin sensitivity and decreased fasting plasma glucose [57]. The disagreement among results could be attributed to different modes of Zn exposure and specific physiological requirements in different individuals. Although Zn plays a vital role in insulin secretion and production, at high levels, it could have adverse effects on FPG. It should be noted that since a large amount of Zn is required for pancreatic islet β-cells, zinc suddenly released under specific conditions might affect the function or survival of islet cells. Therefore, paracrine effects of endogenous Zn cause β cells' death and excess serum zinc may be toxic to the pancreas. Increased Zn in the pancreas has been suggested to cause toxicity to β-cells [58]. Therefore, trace elements toxicity because of different exposure and environmental conditions in future studies should be determined and studied.
According to our study results, gestational diabetes mellitus was more likely to occur in participants who received inadequate RDA-based dietary Mg than in those who had sufficient intake. Furthermore, we found that a negative relationship between mean Mg supplementation and GDM risk. Mg supplementation has been reported to reduce the risk of GDM in hypomagnesemia pregnant women [59]. A recent meta-analysis indicated that Mg supplementation was far more effective than other nutrients supplementation in maintaining glucose metabolic homeostasis and decreasing serum insulin in women with GDM [60]. Mg is required in multiple steps of the insulin-signaling pathways, and the depletion of it can affect the process of glucose metabolism. Mg deficiency could change pancreatic cells' structure, reduce β cell particles, and result in impaired insulin production and secretion [61]. Deficiency of Mg also can mitigate insulin receptor activity and lead to insulin resistance. Hypomagnesemia impedes the glucose uptake in the insulin-stimulated and basal states. Consequently, Mg has an essential role in glucose homeostasis [62].
Our study showed various strengths. We measured gestational weight gain before the diagnosis of GDM, so the confounding effect of GDM treatment on gestational weight gain was eliminated. Also, dietary intake data were assessed in our study, which enabled us to analyze dietary factors and serum trace elements concentrations. Several limitations of our study should also be mentioned. First, the atomic absorption method was not used due to the lack of accessibility. Second, the nature of the case-control study limited us to find causal associations.