Gestational Diabetes Risk Smashed By Vitamin Supplementation
Overview
Exposure to heavy metals has been linked to an increased risk of developing gestational diabetes mellitus (GDM), potentially due to oxidative stress mechanisms. This study aimed to investigate whether vitamin C could influence the relationship between heavy metal exposure and the risk of GDM. A case-control study was conducted in Taiyuan, China, involving 776 GDM cases and 776 controls. Information on vitamin C intake, both from dietary sources and supplements, was obtained through questionnaires. Blood concentrations of heavy metals were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were employed to assess whether vitamin C intake could modify the association between heavy metal exposure and GDM risk.
Introduction
Gestational diabetes mellitus (GDM) occurs when a pregnant woman’s pancreas cannot keep up with the increased insulin demands during pregnancy. In China, the prevalence of GDM rose significantly from 2.3% in 1999 to 9.3% in 2015. GDM is often considered a precursor to Type 2 diabetes mellitus (T2DM), and hyperglycemia during pregnancy has been linked to adverse birth outcomes and long-term health issues for both mothers and their children, such as metabolic syndrome and cardiovascular diseases in mothers, as well as obesity and T2DM in offspring.
Although the exact causes of GDM are not fully understood, research has shown a strong association between GDM and oxidative stress, which refers to an imbalance between oxidants and antioxidants in the body, leading to increased reactive oxygen species (ROS). This oxidative stress can damage islet β-cells, impair insulin secretion, and disrupt glucose metabolism, as seen in various experimental studies. Additionally, oxidative stress has been shown to interfere with the glucose transporter 4 (GLUT4), further reducing glucose transport. Biomarkers of oxidative damage, such as DNA damage and lipid peroxidation products, have also been linked to a higher risk of GDM.
Vitamin C, an essential water-soluble antioxidant, plays a protective role against oxidative stress by scavenging ROS and nitric oxide, preventing damage to DNA, proteins, and lipids. Animal studies have shown that vitamin C can prevent abnormal insulin secretion caused by oxidative stress, thereby reducing the risk of diabetes. Some evidence suggests that vitamin C supplementation can improve insulin sensitivity in people with T2DM, although the relationship between vitamin C and GDM remains inconclusive.
Heavy metals, such as mercury (Hg), nickel (Ni), lead (Pb), and arsenic (As), have been shown to accumulate in pancreatic tissue, contributing to insulin resistance and impairing glucose tolerance. Several epidemiological studies have indicated that higher levels of heavy metal exposure are associated with an increased risk of GDM, likely due to the negative effects of these metals on islet β-cells through oxidative stress pathways. Previous research has found that heavy metal exposure, particularly from Hg, is significantly associated with a higher risk of GDM.
Given the antioxidative properties of vitamin C, it is hypothesized that increased vitamin C intake could mitigate the harmful effects of heavy metals on the risk of GDM. This study analyzed data from the Taiyuan birth cohort study, conducted between 2012 and 2016, to explore the potential protective role of vitamin C in reducing GDM risk associated with heavy metal exposure.
Methods
Inclusion and Exclusion Criteria
Inclusion Criteria:
- Gestational Diabetes Mellitus (GDM) Cases:
– Pregnant women diagnosed with GDM during gestational weeks 24–28 based on the following blood glucose thresholds:
– Fasting blood glucose ≥5.1 mmol/L.
– 1-hour blood glucose >10.0 mmol/L.
– 2-hour blood glucose >8.5 mmol/L.
– Participants must have had a singleton live birth without birth defects.
– Blood samples available for analysis.
- Non-GDM Controls:
– Pregnant women without GDM, matched to cases based on:
– Age (± 2 years).
– Conception time (± 3 months).
– Place of residence.
– Singleton live birth without birth defects.
– Blood samples available for analysis.
Exclusion Criteria:
- Multiple Pregnancies:
– Women with multiple gestations (twins, triplets, etc.) were excluded to avoid complications in assessing GDM risk.
- Birth Defects:
– Women with pregnancies resulting in birth defects were excluded to maintain a consistent population focused on gestational diabetes risk.
- Incomplete Data:
– Participants lacking critical data, such as missing blood samples or incomplete dietary/supplement intake information, were excluded from the study.
- Medical Conditions:
– Women with pre-existing diabetes (Type 1 or Type 2 diabetes mellitus) before pregnancy were excluded to isolate GDM as the primary condition under study.
- Unmatched Controls:
– Non-GDM controls not meeting the frequency matching criteria (age, conception time, and residence) were excluded to ensure comparability between groups.
Vitamin C Supplementation and Dietary Intake
The study evaluated vitamin C supplement use and dietary intake during preconception (the 12 months before pregnancy) and the first trimester (1–13 weeks). GDM diagnoses were made between weeks 24 and 28 of pregnancy. Vitamin C supplement users were those who took either vitamin C alone or multivitamins containing vitamin C during preconception and/or early pregnancy. Dietary intake was assessed using a validated 33-item food frequency questionnaire (FFQ), which covered various food groups such as cereals, meats, dairy, eggs, beans, vegetables, fruits, and seafood. Participants reported the frequency and portion size of each food, which was then converted into grams per day.
Vitamin C intake from the diet was estimated using the Chinese Standard Tables of Food Consumption, and the dietary intake was categorized as either <85 mg/day or ≥85 mg/day, based on the recommended daily allowance for pregnant women. For analysis purposes, vitamin C intake was grouped into three categories: (a) non-supplement users with dietary vitamin C intake <85 mg/day, (b) non-supplement users with dietary vitamin C intake ≥85 mg/day or supplement users with dietary intake <85 mg/day, and (c) supplement users with dietary vitamin C intake ≥85 mg/day.
Analysis
We employed unconditional logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). As per previous research, metals with detectable measurements in ≥80% of samples were categorized into tertiles based on the distribution in the control group. For metals detected in <80% of samples, values below the limit of detection (LOD) were used as the reference group, and measurements above the LOD were split into two groups based on the median concentration among controls. Trend analyses were performed by assigning ordinal values (1, 2, 3) to the tertiles in the models.
To assess whether vitamin C supplementation or dietary intake modifies the association between heavy metal exposure and gestational diabetes mellitus (GDM), we conducted stratified analyses by vitamin C supplement use (users and nonusers) and dietary vitamin C intake (<85 mg/day and ≥85 mg/day). Additionally, we performed combined stratifications of supplement use and dietary intake into three groups: (a) nonusers with <85 mg/day, (b) nonusers with ≥85 mg/day or users with <85 mg/day, and (c) users with ≥85 mg/day. Interaction terms were introduced into multivariate logistic regression models to statistically evaluate potential effect modification.
Potential confounders included parity, month of conception, family history of diabetes, gestational weight gain, physical activity levels, and pre-pregnancy BMI, as previously identified. Statistical significance was determined with a p-value <0.05, and all analyses were conducted using SAS version 9.4.
Results
As previously reported, women with elevated levels of arsenic (As) (OR = 1.49, 95% CI: 1.11-2.01 for the second tertile) and mercury (Hg) (OR = 1.43, 95% CI: 1.09-1.88 for the third tertile) were associated with a higher risk of gestational diabetes mellitus (GDM). After stratifying by vitamin C supplementation, nonusers with higher As exposure had a greater risk of GDM (OR = 1.53, 95% CI: 1.13-2.06 and OR = 1.43, 95% CI: 1.01-2.03 for the second and third tertiles). In contrast, no significant relationship was observed between As exposure and GDM in vitamin C supplement users, and the interaction between As exposure and vitamin C supplementation was statistically significant (Pinteraction = 0.047). No other metals showed significant associations or interactions.
When stratified by dietary vitamin C intake, higher levels of Hg exposure were linked to an increased risk of GDM among women with a vitamin C intake below 85 mg/day (OR = 2.42, 95% CI: 1.48-3.95 and OR = 2.20, 95% CI: 1.30-3.70 for the second and third tertiles). However, this association was not observed among women with a dietary vitamin C intake of 85 mg/day or more, and the interaction between Hg exposure and dietary vitamin C intake was significant (Pinteraction = 0.044).
When considering both vitamin C supplementation and dietary intake, higher Hg levels (OR = 2.36, 95% CI: 1.43-3.92 and OR = 2.04, 95% CI: 1.20-3.46) and As levels (OR = 2.46, 95% CI: 1.37-4.43 and OR = 2.16, 95% CI: 1.12-4.17) were significantly associated with GDM in women who neither used supplements nor met the 85 mg/day dietary vitamin C intake threshold. No significant associations were found in the other groups, and the interactions with Hg and As exposure were statistically significant (Pinteraction = 0.048 and 0.045, respectively).
Conclusion
The study provides evidence supporting the hypothesis that vitamin C supplementation and higher dietary vitamin C intake before and during early pregnancy may reduce the risk of gestational diabetes mellitus (GDM) linked to blood exposure to arsenic (As) and mercury (Hg). Further research with larger sample sizes and samples collected during pregnancy is necessary to confirm these findings.
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