New research reveals that ‘more’ is not always better. Excess micronutrients in early pregnancy may increase the risks of gestational diabetes, urging a rethink on routine supplement use.
Study: Association between blood essential metal elements in early pregnancy and gestational diabetes mellitus. Image credit: StoryTime Studio/Shutterstock.com
Pregnant women must maintain balanced levels of iron (Fe), zinc (Zn), and magnesium (Mg) during early pregnancy to potentially reduce the risk of gestational diabetes mellitus (GDM). A recent Frontiers in Nutrition study investigated the association between early pregnancy trace element levels, particularly Fe, Mg, copper (Cu), Zn, and calcium (Ca), and GDM onset.
Gestational diabetes mellitus during pregnancy
GDM is a type of diabetes that develops during pregnancy in women who have previously had normal glucose metabolism. This condition presents multiple complications during the gestation period. A recent study indicated a surge in the global prevalence of GDM, which could be attributed to higher obesity among women of childbearing age.
GDM has both short-term and long-term effects on the mother and the offspring, including an increased risk of cardiovascular and metabolic diseases, premature delivery, macrosomia, and dystocia. Since the etiology of GDM is unclear, clinicians experience difficulties clinically diagnosing and treating these patients.
Genetic predispositions, social factors, and unhealthy lifestyles are common risk factors for GDM. In addition to gut microbial dysbiosis, an imbalance in essential metal element levels, including Fe, Ca, Zn, Cu, and Mg, could also increase the risk of GDM.
Essential metal elements are recommended as dietary supplements to promote pregnant women's normal physiological and metabolic functions. However, deficiency or excess of these elements could trigger inflammation and oxidative stress, affecting glucose metabolism and insulin sensitivity. These events may significantly increase the risk of GDM. Previous studies suggest that pancreatic β-cells are damaged through alterations in Cu homeostasis, which is associated with the onset of GDM. Furthermore, decreased Mg and Ca levels during specific pregnancy periods have been linked to impaired fasting glucose levels.
Although many studies have indicated a link between essential metal elements and GDM, there have been significant inconsistencies in study findings due to varied methodologies and limited sample sizes. Hence, further research is required to explain the precise relationship between essential metal element levels and GDM. Furthermore, it is necessary to understand the synergistic effects of many essential metal elements on GDM.
About the study
The current study hypothesized that levels of essential metal elements during early pregnancy are associated with the onset of GDM. To test this hypothesis, five different metal elements were assessed in the blood of pregnant women in their first trimester, and individual effects linked to GDM were studied. It must be noted that during early pregnancy, women are typically exposed to higher levels of multiple essential metal elements through additional supplements and diet.
A total of 9,112 pregnant women who met the eligibility criteria were selected for this study. All eligible candidates were between 18 and 45 years of age with a singleton pregnancy. At baseline, an initial pregnancy examination was conducted, and relevant data, such as age, pre-pregnancy height and weight, last menstrual period, maternity history, and medical history of the pregnant women, were collected. During the second and third trimesters, oral glucose tolerance tests (OGTT) were performed in outpatient settings.
Participants were assigned to four groups based on the quartile of five essential metal elements. The risk of GDM at other quantile levels before and after adjusting for covariates was estimated, with the first quantile level as the reference. Restricted cubic splines (RCS) were employed to study the dose-response relationship.
The posterior inclusion probability (PIP) indicated the relative importance of each essential metal element. Weighted quantile sum regression (WQS) and quantile g-computation regression (QGC) models helped perform mixed exposure analysis. Essential metal concentrations were measured using flame atomic absorption spectrometry from whole blood samples.
Study findings
The participants' average age was 30, and their body mass index (BMI) before pregnancy was approximately 20.79 kg/m². In this study cohort, 18.62% of pregnant women were diagnosed with GDM. Higher age, gravidity, parity, and pre-pregnancy BMI were identified as important factors that cause GDM development.
Compared to the non-GDM group, blood analysis revealed that pregnant women who developed GDM had higher levels of essential metal elements, particularly Fe, Cu, and Mg. Pearson correlation analysis revealed a strong positive association between GDM and Fe and Mg, and a negative correlation between Fe and Ca.
After adjusting for BMI, age, parity, and gestational week, the regression model indicated positive correlations between Fe and Mg levels and the risk of GDM. No significant relationship was found between Cu or Ca and GDM.
Analysis by quartiles of essential metal elements revealed that higher quartile levels of Mg, Fe, and Zn were associated with increased risks of GDM. After adjustments, Zn was the only element that correlated positively with GDM risk. RCS analysis revealed a linear positive relationship between Mg (1.42 mmol/L), Fe (7.68 mmol/L), and Zn (87.75 μmol/L) levels and GDM risks. The highest PIP values of Fe indicated that it has the maximum influence on the combined action among all metal elements. No significant additive or multiplicative interactions between the metal elements were found.
Conclusions
The current study confirmed the association between essential metal elements and GDM risks. A higher concentration of Fe, Mg, and Zn in the first trimester of pregnancy correlated with an increased risk of developing GDM. The concentration of blood Fe levels could potentially be used as a biomarker for GDM risk.
However, the study was observational in nature and cannot establish causality.
The current study highlights the importance of consuming essential metal elements appropriately to prevent adverse pregnancy outcomes. Given the complex dose-response relationships, both deficiency and excess may pose risks.
The study authors note that the World Health Organization (WHO) does not currently recommend routine supplementation of Zn and Mg, and Fe supplementation should be carefully considered, particularly for women without Fe deficiency anemia.
More research is required to better understand the collective impact of essential metal elements on GDM development.
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