The present study aimed to detect and analyze the concentrations of 12 trace elements in the sera and placental tissues of pregnant women with GDM in Beijing, China using inductively coupled plasma mass spectrometry. The present results showed that Fe, Cu, Se, and Cr concentrations in the sera of pregnant women with GDM were increased relative to those in the sera of healthy pregnant women. And in placental tissues, Fe concentrations were increased in pregnant women with GDM, but Zn, Mn, Al, and As concentrations were decreased. There was past evidence that trace element status during pregnancy can have a significant impact on maternal and neonatal health outcomes. Although we didn’t have clear evidence yet, it is important to understand the mechanisms involved in these processes[5–7,]. Diabetes is a chronic disease that occurs when the pancreas is no longer able to make insulin or when the body cannot make good use of the insulin it produces. It may be caused by various pathogenic factors, such as genetic factors, immune dysfunction, microbial infections, microbial toxins, free radical toxins, and mental factors, which can act on the body to cause, for example, hypofunction of islets and insulin resistance in response to sugar, protein, fat, and water, as well as causing issues with electrolytes and various metabolic disorder syndromes[]. Oxidative stress is defined as overburdening of the endogenous defense systems by the overproduction of reactive oxygen species (ROS) that threaten cell survival. Oxidative stress plays an important role in the development of complications of diabetes in pregnancy[]. During pregnancy, a condition of progressive insulin resistance occurs in the mother, triggered by placental hormones to ensure the fetus receives adequate nutrients for healthy growth and development. However, when the maternal β-cells were unable to adapt to the metabolic changes accompanying pregnancy, GDM occurs. It is caused by carbohydrate intolerance, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. In glucose tolerance tests, pregnant women show a large increase in blood glucose, and the decrease was delayed; consequently, glucose tolerance was impaired and the incidence of gestational diabetes was increased[]. In this study, some significant differences were found in some trace element concentrations between the GDM and control groups, which may have been caused by changes in the blood glucose levels of pregnant women.
Specifically, Zn and Cu were essential minerals for a variety of biomolecules to maintain the normal cell structure, function and proliferation. According to the results, compared with normal control, GDM cases had increased the level of Zn in the sera, but a barely detectable statistically significant difference. Interestingly, the level of Zn in the placental tissues was decreased. Zn, the IIB group metal, is the 23rd most abundant element in the Earth’s crust. The essential role of Zn in living organisms is mediated by its involvement in a plethora of physiological processes. Particularly, Zn is a component of many enzymes in the body as well as being involved in the structural components of several nucleotides, proteins, and hormones, and functioning in protein synthesis, nucleic acid metabolism, cell division, gene expression, antioxidant defense, and neurological and immune functions. Zn not only maintains the activity of insulin but also produces an insulin-like effect in the body[10]. Several scientific studies had shown that the concentration of maternal serum zinc during pregnancy was associated with GDM incidence. But the study of the correlation between serum zinc and GDM pathogenesis remains a source of controversy. For instance, certain articles report that GDM cases had decreased serum zinc levels relative to normal pregnant women, but others suggest no difference in serum zinc concentrations between GDM women and healthy pregnant women[]. Cu and Zn are antagonistic elements that competitively combine with the same carrier during intestinal absorption. Thus, Cu can inhibit the absorption of Zn, while reduced Zn levels in the body lead to the accumulation of Cu[]. Few epidemiological studies had evaluated the association between copper and glucose levels in pregnant women. Zheng et al.[] evaluated this association prospectively in a pregnant population. Some studies found higher serum copper concentrations among women with GDM, similar to our results, whereas two other case-control studies found no difference in copper concentrations. Ewelina et al. confirmed that the metabolic derangement of glucose and lipid metabolism occurring in diabetes mellitus affects Zn and Cu levels in body fluids(µg/dL) and tissues(mg/kg), which depend on the severity of glucose intolerance and accompanying complications. Also, abnormal metabolism of Zn and Cu can further accelerate diabetic complications[].
In this study, Fe concentrations in the sera and placental tissues of pregnant women with GDM were significantly increased. Greater iron stores within the placentae of women with GDM were consistent with reports that iron excess is associated with an increased risk for GDM[]. However, Controversy still exists about Fe supplementation in pregnant women. Fe is an indispensable trace element in the body; it participates in a series of biochemical activities such as the transport of oxygen, synthesis of DNA, conversion of ATP, and cell respiration. There was evidence that high Fe levels in the body were positively correlated with the occurrence of GDM[6,-]. Kataria et al. performed a meta-analysis investigating the association of Fe biomarkers and dietary Fe exposure with GDM. The findings from this suggested that differences in circulating iron, ferritin, hemoglobin, and transferrin saturation were higher in women with GDM compared to women without GDM, and increased ferritin, hemoglobin, and dietary heme intake were associated with increased odds ratios for GDM[]. In addition to the basic loss of Fe during pregnancy, Fe reserves exist in the placenta and umbilical cord. Thus, during pregnancy, the demand for Fe gradually increases over time, which reduces the Fe available in sera. Routine Fe supplementation was therefore recommended from the second trimester until full-term pregnancy. Placental tissue, which was shared by the mother and the fetus, can not only transport nutrients between the two but also acts as a protective barrier against heavy metals[]. Fe deficiency i.e., anemia, was a common disease during pregnancy; It can cause low weight and premature delivery. It can prevent maternal deficiencies and anemia, but there is little evidence of the relationship between Fe metabolism and insulin resistance[]. FAO/WHO (1988) data show that the Fe reserves required to meet the needs of fetal growth and Fe reserves in the placenta over about 93 days in early, mid, and late pregnancy were 25, 100, and 190 mg, respectively[].
Se has been found for 200 years and is an essential micronutrient for mammals; it is an important component of many enzymes in the body, and it can play an important role in antioxidation, delaying the signs of aging, and enhancing immunity. Previous studies had also found that adequate selenium intake is essential for the immune system, the endocrine system, the cardiovascular system, the reproductive system, and the nervous system[]. The lack of Se in the human body was associated with more than diseases including cancer, cardiovascular disease, liver disease, cataracts, pancreatic disease, diabetes, and reproductive system disease It should be emphasized that either too high level of selenium or its deficiency was harmful to human health. For example, Se supplementation can prevent acute Keshan disease, whereas alopecia was closely related to excessive Se intake[5–6,]. Wang et al. studied the association between serum selenium levels and type 2 diabetes mellitus and found that a positive correlation between serum selenium levels and T2DM existed in the population with relatively low and high serum selenium levels, which indicated that serum selenium was closely related to T2DM. There may be a U-shaped nonlinear dose-response relationship[]. Zeng et al. also found that a high-selenium diet did induce moderate GDM and postpartum insulin resistance in neonatal rats[]. In the USA[], Italy[], France[], and other countries, the intake of Se had also been related to the risk of diabetes, but epidemiological investigations have yet to reach a definite conclusion on this issue. Notably, the Se status is suggested to be critical in Se supplementation-mediated health effects. Accordingly, it was estimated that the beneficial effect of Se supplementation on human health should be largely seen in subjects with serum or plasma Se concentration less than 122 µg/L. In contrast, Se administration to patients with a serum or plasma Se concentration of 122 µg/L or higher has been associated with an increased risk of nonmelanoma skin cancer and type 2 diabetes[]. The CNHS 2010–2012 was a nationally representative cross-sectional study. Liu et al. studies had established reference values of 14 serum trace elements for pregnant women selected from the CNHS, the range of sera Se concentration was 0.07 (0.04–0.11) µg/mL[]. The present results also showed that serum Se levels in GDM patients were 0.15 µg/mL, and that of healthy pregnant subjects were 0.08 µg/mL, which were significantly higher in GDM groups than in healthy pregnant women. Therefore, the serum selenium level of pregnant women may be related to diabetes.
To investigate the relationship between Se concentrations and activities of GPX in the Placenta of GDM pregnant women, the activities of GPX isozymes in the Placenta of GDM pregnant women were determined. The final results showed that the activity of GPX1 groups was higher than that of the other groups, but unfortunately there was no statistically significant difference between the groups, and the activity of GPX 2–4 groups was not different between the two groups; that means, there was no difference in the level of selenium in placental tissue between the two groups. The physiological role of GPXs is mediated by its involvement in redox regulation of cell functions. Physiological functions of Se are mainly mediated through Se-containing proteins, selenoproteins, containing Se in the form of selenocysteine. More than 50 Selenoprotein families have been identified, of which only 25 exist in humans, and GPX1 is the first human selenoprotein to demonstrate its function[27].Some studies had shown that the levels of GPX and Se in patients with GDM are closely related to the occurrence and development of GDM[9][]. Perhaps because of the small sample size involved in this study, further exploration is needed.
Furthermore, pregnant women were affected by many factors other than micronutrient levels. Some studies had indicated that maternal age, obesity, number of abortions, pregnancy time, impaired carbohydrate tolerance before pregnancy, and family history of diabetes were the main risk factors for GDM, which increases maternal and fetal complications[1,4,]. If women were overweight or obese in prepregnancy, their incidence of GDM was significantly higher than that of pregnant women with low or normal weight[]. Lin’s survey of nearly 5,000 pregnant women in China showed that an increase in prepregnancy BMI led to an increase in the detection rate of GDM patients and the proportion of patients with two or more abnormalities in OGTTs []. In 2014, the Obstetrics Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association issued the “Guidelines for the Diagnosis and Treatment of Diabetes in Pregnancy." According to different BMIs before pregnancy, the recommended standards for the intake of energy and nutrients for different gestational weeks were clarified to formulate GDM nutritional treatments. The 2017 International Conference on Diabetes Mellitus in Pregnancy advocated for the need to attend to GDM and encouraged patients to receive prepregnancy consultation, pregnancy care, and postnatal follow-up sessions[]. In the present study, there were no significant differences in age, BMI, and newborn weight between pregnant women with and without GDM.
However, there were limitations to this study. First, We only compared the content of some trace elements in GDM and health pregnant women, and could not determine the nutritional and environmental factors that may affect the depth of elements in the analyzed samples. Secend, the sample size was small, and it is more convincing to expand the sample size. But our conclusion should be correct, and we can already see this trend.
In summary, the changes in trace elements found in GDM patients in the current study can help provide further guidelines for the prevention of and intervention of GDM. These findings will help researchers to understand the pathogenesis of diabetes about trace element deficiency or excess, as well as the need to further elucidate the related trace elements. the data provide support for understanding the pathogenesis and development process of diabetes, and they provide a theoretical basis for the analysis of trace elements in the prevention and control of diabetes. However, based on the risk of GDM in the pregnant population in China, it remains necessary to conduct relevant research on a much larger population.