Increased Risk Of Gestational Diabetes Mellitus Research Articles

Impact of Vitamin D Deficiency on Gestational Diabetes and Pregnancy Outcomes Across Diverse Ethnic Groups: A Retrospective Cohort Study

Background: Vitamin D deficiency is linked to adverse pregnancy outcomes like gestational diabetes mellitus (GDM), but its effects across ethnic groups are unclear. This study examines the relationship among vitamin D levels, glucose tolerance, GDM prevalence, and neonatal outcomes in a multi-ethnic cohort of pregnant women. Methods: We conducted a retrospective analysis of 252 pregnant women from antenatal clinics between 2018 and 2022. Participants were divided into four groups based on serum vitamin D levels: severely deficient (<25 nmol/L), deficient (25–50 nmol/L), insufficient (51–75 nmol/L), and sufficient (>75 nmol/L). The analysis included multivariate linear regression models adjusted for age, ethnicity, BMI, gestational diabetes status, and seasonality. An area under the receiver operating characteristic (AUROC) analysis identified the vitamin D threshold linked to an increased GDM risk. Results: Women classified as severely deficient had higher fasting glucose levels (5.73 ± 1.24 mmol/L) than those in other groups (p = 0.003, adjusted). The AUROC analysis identified a vitamin D threshold of 45 nmol/L associated with an elevated GDM risk (AUROC = 0.78, CI: 0.70–0.85). South Asian women had lower vitamin D levels (41.17 ± 18.03 nmol/L vs. 45.15 ± 16.75 nmol/L) and higher glucose tolerance test (GTT) levels than Caucasian women, despite having lower BMIs. Moreover, vitamin D levels positively correlated with neonatal birth weight (p = 0.02). Conclusions: There is a strong link between vitamin D deficiency and increased GDM risk, especially among South Asian women. These findings underscore the need for targeted interventions to improve vitamin D levels in high-risk ethnic groups.

Maternal Macronutrient Intake and Associated Risk for Gestational Diabetes Mellitus: Results from the BORN2020 Study.

Background/Objectives: Limited evidence links maternal macronutrient intake to gestational diabetes mellitus (GDM) risk. Therefore, we evaluated these intakes both before and during pregnancy, comparing macronutrient data against the European Food and Safety Authorities' (EFSA) Dietary Reference Values (DRVs). Methods: Data were prospectively collected from the Greek BORN2020 epidemiologic pregnant cohort, which included 797 pregnant women, of whom 14.7% were diagnosed with GDM. A multinomial logistic regression model assessed the association between macronutrient intake and GDM, adjusting for maternal, lifestyle, and pregnancy-related factors. Results: Women with GDM had higher maternal age (34.15 ± 4.48 vs. 32.1 ± 4.89 years), higher pre-pregnancy BMI (median 23.7 vs. 22.7 kg/m2), and were more likely to smoke during mid-gestation (17.95% vs. 8.82%). Pre-pregnancy energy intake exceeding EFSA recommendations was associated with increased GDM risk (aOR = 1.99, 95%CI: 1.37-2.86). During mid-gestation, higher dietary fiber intake (aOR = 1.05, 95%CI: 1.00-1.10), higher protein intake (aOR = 1.02, 95% CI: 1.00-1.04), and higher protein percentage of energy intake (aOR = 1.08, 95%CI: 1.01-1.17) were all significantly associated with increased GDM risk. Changes from pre-pregnancy to pregnancy showed significant increases in dietary fiber intake (aOR = 1.07, 95%CI: 1.04-1.10), protein (aOR = 1.00, 95%CI: 1.00-1.01), fat (aOR = 1.00, 95%CI: 1.00-1.01), vegetable protein (aOR = 1.01, 95%CI: 1.00-1.03), animal protein (aOR = 1.00, 95%CI: 1.00-1.01), and monounsaturated fatty acid (MUFA) intake (aOR = 1.01, 95%CI: 1.00-1.02), all of which were associated with increased GDM risk. Conclusions: Energy intake above upper levels set by EFSA, as well as increased protein, MUFA, and fiber intake, although beneficial in balanced intakes, may negatively affect gestation by increasing GDM likelihood when consumed beyond requirements.

Gestational Diabetes Mellitus and Chemical Exposure

Gestational diabetes mellitus (GDM) is a common pregnancy complication with significant implications for maternal and fetal health. Recent studies suggest environmental chemical exposure, particularly to endocrine-disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) and phthalates, may be a novel risk factor for GDM. This meta-analysis investigates the association between exposure to environmental chemicals and the risk of developing GDM using random-effects models by comprehensive electronic search carried out in the EMBASE, PubMed, and Web of Science databases for relevant studies from their inception to November 2021. The pooled odds ratio (OR) for the association between environmental chemical exposure and gestational diabetes mellitus (GDM) is approximately 5.923, with a 95% confidence interval (CI) ranging from 5.314 to 6.60 which is a statistically significant association between higher levels of environmental chemical exposure and increased GDM risk. The findings underscore the need for public health strategies aimed at reducing exposure to harmful chemicals among pregnant women to mitigate GDM risk.

Pre-pregnancy LDL/HDL and total Cholesterol/HDL ratios are strong predictors of gestational diabetes mellitus in women undergoing assisted reproductive technologies

Background & ObjectiveTo analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest.MethodsData was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides).Results119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p < 0.05), but TC and TG did not. Binary LDL/HDL and TC/HDL ratios showed the strongest association with GDM incidence (OR 1.957 [95%CI 1.258–3.044] and 1.942 [1.243–3.034] respectively). Subgroup analysis showed that an elevated LDL/HDL ratio also increased GDM risk in subgroups with a typically lower prevalence of GDM, such as young women with a low BMI and low blood pressure. Both lipid ratios (LDL/HDL and TC/HD) show strong interactions with baseline age, fasting plasma glucose, and LH.ConclusionsIn this cohort of Chinese women undergoing ART, pre-pregnancy LDL/HDL and TC/HDL were associated with GDM the strongest from the lipid parameters and could be useful to estimate GDM risk even before ART treatments and pregnancy.Clinical trial numberNCT03503006 registered on the 21st of March 2018 (on clinicaltrials.gov). https://clinicaltrials.gov/study/NCT03503006?locStr=Changsha,%20Hunan,%20China&country=China&state=Hunan&city=Changsha&cond=ivf&rank=2.

Association of maternal blood metabolomics and gestational diabetes mellitus risk: a systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has short- and long-term adverse effects. Therefore, further exploration of the pathophysiology of GDM and related biomarkers is important. In this study, we performed a systematic review and meta-analysis to investigate the associations between metabolites in blood detected via metabolomics techniques and the risk of GDM and to identify possible biomarkers for predicting the occurrence of GDM. We retrieved case‒control and cohort studies of metabolomics and GDM published in PubMed, Embase, and Web of Science through March 29, 2024; extracted metabolite concentrations, odds ratios (ORs), or relative risks (RRs); and evaluated the integrated results with metabolites per-SD risk estimates and 95% CIs for GDM. We estimated the results via the random effects model and the inverse variance method. Our study is registered in PROSPERO (CRD42024539435). We included a total of 28 case‒control and cohort studies, including 17,370 subjects (4,372 GDM patients and 12,998 non-GDM subjects), and meta-analyzed 67 metabolites. Twenty-five of these metabolites were associated with GDM risk. Some amino acids (isoleucine, leucine, valine, alanine, aspartate, etc.), lipids (C16:0, C18:1n-9, C18:1n-7, lysophosphatidylcholine (LPC) (16:0), LPC (18:0), and palmitoylcarnitine), and carbohydrates and energy metabolites (glucose, pyruvate, lactate, 2-hydroxybutyrate, 3-hydroxybutyrate) were discovered to be associated with increased GDM risk (hazard ratio 1.06-2.77). Glutamine, histidine, C14:0, and sphingomyelin (SM) (34:1) were associated with lower GDM risk (hazard ratio 0.75-0.84). These findings suggest that these metabolites may play essential roles in GDM progression, and serve as biomarkers, contributing to the early diagnosis and prediction of GDM.

Is Polyhexamethylene Guanidine and Oligo(2-(2-Ethoxy) Ethoxyethyl Guanidium Chloride Exposure Related to Gestational Diabetes?

This study aims to investigate the association between exposure to toxic indoor chemicals, specifically polyhexamethylene guanidine (PHMG) and oligo(2-(2-ethoxy) ethoxyethyl guanidinium) chloride (PGH), used in humidifier disinfectants, and gestational diabetes mellitus (GDM). We confirmed pregnancy from 2003 to 2017 and identified GDM by linking a cohort of claimants who reported exposure to PHMG/PGH with National Health Insurance Service data. The GDM incidence was calculated, and PHMG/PGH exposure characteristics-exposure status, the humidifier's distance/location, and exposure duration/hours-were investigated. Logistic regression and mediation analysis were applied using asthma, frequently treated with steroids, as a mediator. Among 521 pregnancies, 38 were identified as GDM, with 2.4% before exposure and 8.9% after exposure. Pregnancies after exposure had a higher odds ratio (OR) for GDM (OR 2.968, 95% CI: 1.004-12.725). A trend of increased GDM risk was observed with longer exposure duration/hours. Additionally, pregnancies after exposure demonstrated total and direct effects on GDM (β = 0.0435, p = 0.036, β = 0.0432, p = 0.030) independent of the indirect effects by asthma. The incidence of GDM was higher after PHMG/PGH exposure compared to before. PHMG/PGH exposure was associated with GDM, independent of asthma. Further research is warranted to confirm these findings in exposed cohorts and to explore the underlying mechanisms.

Associations of maternal serum ferritin levels across gestation with gestational diabetes mellitus: A longitudinal cohort study.

The longitudinal changes in maternal serum ferritin (SF) levels across gestation, which indirectly reflect iron supplementation, have not been extensively investigated in relation to gestational diabetes mellitus (GDM). We conducted a retrospective cohort study at a tertiary maternal hospital in Shanghai. Women with SF concentration measurements at 8.0-13.6 weeks' gestation (GW), 29.0-31.6 GW, and an oral glucose tolerance test (OGTT) at 24-28 GW were included. We utilized logistic regression analysis to assess GDM association with maternal SF levels and longitudinal changes. The study included 17 560 women, with 2160 (12.3%) participants diagnosed with GDM. Adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for GDM across increasing quartiles of SF concentrations at 8.0-13.6 GW were 1.00 (reference), 1.139 (95% CI: 1.012-1.283), 1.093 (95% CI: 0.969-1.233), and 1.248 (95% CI: 1.111-1.403). Similarly, at 29.0-31.6 GW, increasing quartiles of SF concentrations were associated with higher adjusted ORs for GDM: 1.00 (reference), 1.165 (95% CI: 1.029-1.320), 1.335 (95% CI: 1.184-1.505), and 1.428 (95% CI: 1.268-1.607). Pregnant women with higher SF levels (upper 25th percentile) at 8.0-13.6 GW had a reduced GDM risk if their SF levels decreased to the lower 25th percentile at 29.0-31.6 GW. Conversely, the subgroup with higher SF levels (upper 25th percentile) at both time points had the highest incidence rate of GDM (15.3%, 1.235 [95% CI: 1.087-1.404]). Maternal SF levels independently and positively associated with GDM risk during early and late gestational stages. Considering the increased GDM risk, routine iron supplementation for iron-replete women is questionable.

Titanium exposure and gestational diabetes mellitus: associations and potential mediation by perturbation of amino acids in early pregnancy

BackgroundSeveral recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce.MethodsThe present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways.ResultsAs parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk.ConclusionsIn this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.Graphical

Circulating glycated albumin levels and gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is first diagnosed during pregnancy, making it the most common complication associated with this period. Early detection and targeted treatment of GDM can minimize foetal exposure to maternal hyperglycaemia and subsequently reduce the associated adverse pregnancy outcomes. Previous studies have inconsistently suggested that the level of glycated albumin (GA) might predict GDM. To review and synthesize existing evidence to evaluate the relationship between GA levels and the development of GDM. We sought to compare GA levels between GDM and control groups in this meta-analysis by systematically searching the Web of Science, PubMed, Cochrane Library, and Embase databases for articles published up to June 2023. The analysis utilized the weighted mean difference (WMD) as the primary metric. The data were meticulously extracted, and the quality of the included studies was assessed. Additionally, we conducted a subgroup analysis based on study region and sample size. We assessed heterogeneity using I 2 statistics and evaluated publication bias through funnel plots. Additionally, trim-and-fill analysis was employed to detect and address any potential publication bias. The meta-analysis included a total of 11 studies involving 5477 participants, comprising 1900 patients with GDM and 3577 control individuals. The synthesized results revealed a notable correlation between elevated GA levels and increased susceptibility to GDM. The calculated WMD was 0.42, with a 95% confidence interval (95%CI) ranging from 0.11 to 0.74, yielding a P value less than 0.001. Concerning specific GA levels, the mean GA level in the GDM group was 12.6, while for the control group, it was lower, at 11.6. This discrepancy underscores the potential of GA as a biomarker for assessing GDM risk. Moreover, we explored the levels of glycated haemoglobin (HbA1c) in both cohorts. The WMD for HbA1c was 0.19, with a 95%CI ranging from 0.15 to 0.22 and a P value less than 0.001. This observation suggested that both GA and HbA1c levels were elevated in individuals in the GDM group compared to those in the control group. Our meta-analysis revealed a substantial correlation between elevated GA levels and increased GDM risk. Furthermore, our findings revealed elevated levels of HbA1c in GDM patients, emphasizing the significance of monitoring both GA and HbA1c levels for early GDM detection and effective management.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study

Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR)=1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR=1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Triglyceride-glucose index in early pregnancy predicts the risk of gestational diabetes: a prospective cohort study

ObjectiveThis study aimed to investigate the association between the triglyceride-glucose (TyG) index in early pregnancy and the development of gestational diabetes mellitus (GDM) in the second trimester. The primary objectives were to evaluate the predictive potential of the TyG index for GDM, determine the optimal threshold value of the TyG index for GDM assessment, and compare the predictive performance of the TyG index alone versus its combination with maternal age and pre-pregnancy body mass index on GDM. Moreover, the study explored the association between the TyG index in early pregnancy and the risk of other pregnancy-related complications (PRCs), such as placental abruption and gestational hypertension.Patients and methodsThis prospective cohort study recruited 1,624 pregnant women who underwent early pregnancy antenatal counseling and comprehensive assessments with continuous monitoring until delivery. To calculate the TyG index, health indicators, including maternal triglycerides and fasting plasma glucose, were measured in early pregnancy (< 14 weeks of gestation). The predictive power of the TyG index for evaluating GDM in Chinese pregnant women was determined using multifactorial logistic regression to derive the odds ratios and 95% confidence interval (CI). Subgroup analyses were conducted, and the efficacy of the TyG index in predicting PRCs was assessed via receiver operating characteristic (ROC) curve analysis and restricted cubic spline, with the optimal cutoff value calculated.ResultsLogistic regression analyses revealed a 2.10-fold increase in the GDM risk for every 1-unit increase in the TyG index, after adjusting for covariates. The highest GDM risk was observed in the group with the highest TyG index compared with the lowest quintile group (odds ratios: 3.25; 95% CI: 2.23–4.75). Subgroup analyses indicated that exceeding the recommended range of gestational weight gain and an increased GDM risk were significantly associated (P = 0.001). Regarding predictive performance, the TyG index exhibited the highest area under the curve (AUC) value in the ROC curve for GDM (AUC: 0.641, 95% CI: 0.61–0.671). The optimal cutoff value was 8.890, with both sensitivity and specificity of 0.617.The combination of the TyG index, maternal age, and pre-pregnancy body mass index proved to be a superior predictor of GDM than the TyG index alone (AUC: 0.672 vs. 0.641, P < 0.01). After adjusting for multiple factors, the analyses indicated that the TyG index was associated with an increased risk of gestational hypertension. However, no significant association was noted between the TyG index and the risk of preeclampsia, placental abruption, intrauterine distress, or premature rupture of membranes.ConclusionThe TyG index can effectively identify the occurrence of GDM in the second trimester, aligning with previous research. Incorporating the TyG index into routine clinical assessments of maternal health holds significant practical implications. Early identification of high-risk groups enables healthcare providers to implement timely interventions, such as increased monitoring frequency for high-risk pregnant women and personalized nutritional counseling and health education. These measures can help prevent or alleviate potential maternal and infant complications, thereby enhancing the overall health outcomes for both mothers and babies.

Associations of legacy perfluoroalkyl and polyfluoroalkyl substances, alternatives, and isomers with gestational diabetes mellitus and glucose homeostasis among women conceiving through assisted reproduction in Shanghai, China.

Prior research has reported that perfluoroalkyl and polyfluoroalkyl substances (PFAS) may be linked to impaired glucose homeostasis in pregnant women. However, few studies have investigated PFAS alternatives and isomers, and even less is known about the association among women conceiving through assisted reproductive technology (ART). The prospective cohort study aimed to explore associations of legacy PFAS, alternatives and isomers with gestational diabetes mellitus (GDM) and glucose homeostasis during pregnancy among 336 women conceiving through ART. Nineteen PFAS, including nine linear legacy PFAS, four short-chain alternatives, four branched isomers, and two emerging PFAS alternatives, were determined in first-trimester maternal serum. Fasting plasma glucose (FPG), 1-h and 2-h glucose concentrations following the oral glucose tolerance test (OGTT), and glycated hemoglobin (HbA1c) were measured during the second trimester. After adjusting for confounding variables, nearly half of individual PFAS (10/19) and PFAS mixtures were correlated with increased GDM risk or elevated 2-h glucose levels. Among PFAS congeners, emerging PFAS alternatives, chlorinated perfluoroalkyl ether sulfonic acids (Cl-PFESAs), showed a notable association with impaired glucose homeostasis. For example, 6:2 Cl-PFESA exhibited a correlation with GDM (OR = 1.31, 95% CI = 1.02, 1.68) and 2-h glucose concentrations (β = 0.22, 95% CI = 0.08, 0.36), and contributed most to the overall association with 2-h glucose concentrations. Compared to those diagnosed with male factor infertility, the associations were more pronounced in infertile women with reproductive endocrine diseases. We provide evidence that exposure to PFAS, especially emerging PFAS alternatives, may impair glucose homeostasis and increase the risk of GDM among women conceiving through ART.

Maternal Serum Copper and Some Metabolic Indexes in Late Second Trimester of Gestational Diabetes Mellitus Pregnancy.

Copper (Cu) is a physiologically important trace element during pregnancy. The study aim is to assess the altered level of serum Cu and its association with some metabolic indexes in Gestational Diabetes Mellitus (GDM). A total of 108 pregnant women (aged 18 - 40, second trimester) are included in the study and divided into two groups (GDM n = 54; pregnant with normal glucose tolerance (NGT), n = 54) after performing a 2-hour 75-g oral glucose tolerance test (OGTT). Maternal blood samples are collected at 26 - 28 gestational week. All biochemical parameters are measured in serum from fasting venous blood. Serum Cu levels are analyzed by flame atomic absorption spectrophotometry (Perkin Elmer AAnalyst 300, USA). Body Mass Index (BMI), insulin sensitivity/resistance, triglyceride-glucose (TyG), TyG-BMI (triglyceride glucose-body mass) indexes are calculated by formulas. The following data were observed: significantly higher levels of serum Cu (p = 0.009), pre-pregnancy BMI (pre-pBMI), BMI at the GDM diagnosis (pBMI), TyG, pregnancy TyG-BMI (pTyG-BMI) p < 0.001, and triglycerides (Tgl) (p = 0.02) in GDM compared to NGT pregnancy. The study presents a positive correlation between serum Cu and pre-pBMI (p < 0.02), pBMI and pTyG-BMI (p < 0.001). Besides, pre-pBMI (mean ≥ 25 kg/m2), pBMI (mean ≥ 30 kg/m2), and pTyG-BMI are associated with 14.5% (OR 1.145, 95% CI: 1.064 - 1.232; p < 0.001), 15.3% (OR 1.153, 95% CI: 1.070 - 1.243; p < 0.001), and 5.9% (OR 1.059, 95% CI: 1.022 - 1.086; p < 0.001) increased risk for GDM development. No association is found between Cu and Tgl levels, fasting plasma glucose e(FPG) and TyG. ROC analysis suggests the serum Cu as a possible risk factor for GDM development. The analysis shows that at a cutoff point of ≥ 31.9 µmol/L, serum Cu presents a sensitivity and specificity of 64.8% and 66.7% in the prediction of GDM development (AUC = 0.659, p < 0.012). After adjustment for maternal age, gestational age, and family predisposition, the odds ratios (ORs) (95% CIs) still show association of Cu levels with increased GDM risk (OR 1.099, 95% CI 1.018 - 1.184, p = 0.013). pTyG-BMI index exhibits a better interaction than TyG index, Tgl, and glucose separately with serum Cu levels where BMI has a mediator's role.

Potential Protective Effect of Anti-zinc Transporter 8 Autoantibodies on Gestational Diabetes Mellitus in Iraqi Population

Background:The human zinc transporter 8 (ZNT8), also known as the solute carrier family 30A, member 8 (SLC30A8), is a β-cell specific integral membrane protein, mainly restricted to the membrane of insulin secretory granules. ZnT8 plays a crucial role in both insulin synthesis and secretion as well as the viability of β-cells. The recently identified autoantibodies targeting the β-cell surface epitopes of ZnT8 have been proposed as a new risk factor for gestational diabetes mellitus (GDM). Due to the lack of prior research studies on the role of β-cell surface autoantibodies against ZnT8 in the immunologic etiology of GDM in Iraqi population, this study has been designed to explore the association between the rs13266634 C&gt;T polymorphism in the SLC30A8 gene and the serum levels of ZnT8 as well as Zinc Transporter-8 Autoantibody (ZnT8A) in women diagnosed with GDM.Methods:A total of 50 participants with GDM and 50 controls from the Baghdad Teaching Hospital/Pregnancy Care unit at the Medical City, Baghdad, Iraq, were recruited in this case–control study. Serum levels of ZnT8 and ZnT8A were assayed with enzyme-linked immunosorbent assay, and Taqman real time polymerase chain reaction (RT-PCR) was used for rs13266634 single nucleotide polymorphism (SNP) genotyping.Results:ZnT8A levels were significantly lower in women with GDM than non-GDM women (P≤ 0.01). A ZnT8A level lower than 20.0 pg/mL was significantly associated with a threefold higher risk for GDM withP≤ 0.001. ZnT8 levels were significantly higher in the GDM subjects (P≤ 0.05). The T allele at the rs13266634 C&gt;T SNP significantly conferred a higher risk of GDM (P= 0.002). In view of that, the TT genotype, compared to the CC genotype, showed a significant association with increased GDM risk (P≤ 0.01). Serum ZnT8A concentrations were significantly low among GDM women who had CT genotype (P= 0.003).Conclusion:The T variant at the SLC30A8 rs13266634 C&gt;T polymorphism appears to play a key role in determining the β-cell autoimmunity by inducing an autoantibody response due to its hyperactivity of zinc transportation.

The Influence of Airborne Particulate Matter on the Risk of Gestational Diabetes Mellitus: A Large Retrospective Study in Chongqing, China.

Emerging research findings suggest that airborne particulate matter might be a risk factor for gestational diabetes mellitus (GDM). However, the concentration-response relationships and the susceptible time windows for different types of particulate matter may vary. In this retrospective analysis, we employ a novel robust approach to assess the crucial time windows regarding the prevalence of GDM and to distinguish the susceptibility of three GDM subtypes to air pollution exposure. This study included 16,303 pregnant women who received routine antenatal care in 2018-2021 at the Maternal and Child Health Hospital in Chongqing, China. In total, 2482 women (15.2%) were diagnosed with GDM. We assessed the individual daily average exposure to air pollution, including PM2.5, PM10, O3, NO2, SO2, and CO based on the volunteers' addresses. We used high-accuracy gridded air pollution data generated by machine learning models to assess particulate matter per maternal exposure levels. We further analyzed the association of pre-pregnancy, early, and mid-pregnancy exposure to environmental pollutants using a generalized additive model (GAM) and distributed lag nonlinear models (DLNMs) to analyze the association between exposure at specific gestational weeks and the risk of GDM. We observed that, during the first trimester, per IQR increases for PM10 and PM2.5 exposure were associated with increased GDM risk (PM10: OR = 1.19, 95%CI: 1.07~1.33; PM2.5: OR = 1.32, 95%CI: 1.15~1.50) and isolated post-load hyperglycemia (GDM-IPH) risk (PM10: OR = 1.23, 95%CI: 1.09~1.39; PM2.5: OR = 1.38, 95%CI: 1.18~1.61). Second-trimester O3 exposure was positively correlated with the associated risk of GDM, while pre-pregnancy and first-trimester exposure was negatively associated with the risk of GDM-IPH. Exposure to SO2 in the second trimester was negatively associated with the risk of GDM-IPH. However, there were no observed associations between NO2 and CO exposure and the risk of GDM and its subgroups. Our results suggest that maternal exposure to particulate matter during early pregnancy and exposure to O3 in the second trimester might increase the risk of GDM, and GDM-IPH is the susceptible GDM subtype to airborne particulate matter exposure.

Gestational diabetes mellitus in pregnancies conceived after infertility treatment: a population-based study in the United States, 2015–2020

To evaluate the risk of gestational diabetes mellitus (GDM) in singleton pregnancies conceived using infertility treatment and examine the influence of race and ethnicity as well as prepregnancy body mass index (BMI). Cross-sectional study using the US vital records data of women that delivered singleton births. United States, 2015-2020. Any infertility treatment was divided into two groups: those that used fertility-enhancing drugs, artificial insemination, or intrauterine insemination, and those that used assisted reproductive technology (ART). Gestational diabetes mellitus, defined as a diagnosis of diabetes mellitus during pregnancy, includes both diet-controlled GDM and medication-controlled GDM in singleton pregnancies conceived with infertility treatment or spontaneously and delivered between 20- and 44-weeks' gestation. We also examined whether the infertility treatment-GDM association was modified by maternal race and ethnicity as well as prepregnancy BMI. Associations were expressed as a rate ratio (RR) and 95% confidence interval (CI), derived from log-linear models after adjustment for potential confounders. A total of 21,943,384 singleton births were included, with 1.5% (n = 318,086) undergoing infertility treatment. Rates of GDM among women undergoing infertility treatment and those who conceived spontaneously were 11.0% (n = 34,946) and 6.5% (n = 1,398,613), respectively (adjusted RR 1.24, 95% CI 1.23, 1.26). The RRs were adjusted for maternal age, parity, education, race and ethnicity, smoking, BMI, chronic hypertension, and year of delivery. The risk of GDM was modestly increased for those using fertility-enhancing drugs (adjusted RR 1.28, 95% CI 1.27, 1.30) compared with ART (adjusted RR 1.18, 95% CI 1.17, 1.20), and this risk was especially apparent for non-Hispanic White women (adjusted RR 1.29, 95% CI 1.26, 1.31) and Hispanic women (adjusted RR 1.35, 95% CI 1.29, 1.41). The number of women who needed to be exposed to infertility treatment to diagnose one case of GDM was 46. Prepregnancy BMI did not modify the infertility treatment-GDM association overall and within strata of race and ethnicity. These general patterns were stronger after potential corrections for misclassification of infertility treatment and unmeasured confounding. Infertility treatment, among those who received fertility-enhancing drugs, is associated with an increased GDM risk. The persistently higher risk of GDM among women who seek infertility treatment, irrespective of prepregnancy weight classification, deserves attention. Infertility specialists must be vigilant with preconception counseling and ensure that all patients, regardless ofrace and ethnicity or BMI, are adequately tested for GDM early in pregnancy using a fasting blood glucose level or a traditional 50-g oral glucose tolerance test. Testing may be completed by the infertility specialist or deferred to the primary prenatal care provider at the first prenatal visit.

Serum Sulfur-Containing Amino Acids and Risk of Maternal Gestational Diabetes and Adverse Growth Patterns in Offspring.

To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring. We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring. High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18-3.13 and 2.69, 1.59-4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64-4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09-7.17 and 3.92, 1.11-13.89) and the effect was largely independent of GDM. High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.

PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort

BackgroundPer- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk.MethodsIn the PETALS pregnancy cohort, a nested case–control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR).ResultsPFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant.ConclusionsHigher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.

Preconceptional and prenatal exposure to air pollutants and risk of gestational diabetes in the MADRES prospective pregnancy cohort study

Air pollution has been associated with gestational diabetes mellitus (GDM). We aim to investigate susceptible windows of air pollution exposure and factors determining population vulnerability. We ascertained GDM status in the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort from Los Angeles, California, USA. We calculated the relative risk of GDM by exposure to ambient particulate matter (PM10; PM2.5), nitrogen dioxide (NO2), and ozone (O3) in each week from 12 weeks before to 24 weeks after conception, adjusting for potential confounders, with distributed lag models to identify susceptible exposure windows. We examined effect modification by prenatal depression, median-split pre-pregnancy BMI (ppBMI) and age. Sixty (9.7%) participants were diagnosed with GDM among 617 participants (mean age: 28.2 years, SD: 5.9; 78.6% Hispanic, 11.8% non-Hispanic Black). GDM risk increased with exposure to PM2.5, PM10, and NO2 in a periconceptional window ranging from 5 weeks before to 5 weeks after conception: interquartile-range increases in PM2.5, PM10, and NO2 during this window were associated with increased GDM risk by 5.7% (95% CI: 4.6-6.8), 8.9% (8.1-9.6), and 15.0% (13.9-16.2), respectively. These sensitive windows generally widened, with greater effects, among those with prenatal depression, with age ≥28 years, or with ppBMI ≥27.5kg/m2, than their counterparts. Preconception and early-pregnancy are susceptible windows of air pollutants exposure that increased GDM risk. Prenatal depression, higher age, or higher ppBMI may increase one's vulnerability to air pollution-associated GDM risk. National Institutes of Health, Environmental Protection Agency.

A comprehensive meta-analysis on the association between vitamin C intake and gestational diabetes mellitus: Insights and novel perspectives.

Gestational Diabetes Mellitus (GDM) is a significant health concern in pregnant women and their offspring. Although Vitamin C is known to play a role in maintaining normal physiological processes, its relationship with GDM has not been fully elucidated. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, analyzing data from 15 studies selected from PubMed, Embase, Web of Science, and the Cochrane Library up to May 16, 2023. These studies were selected based on inclusion criteria such as study design, outcome of interest, exposure factor, and data extractability. Quality assessment was performed using the Newcastle-Ottawa Scale. We assessed the heterogeneity between studies and conducted a sensitivity analysis. Data from 10,131 subjects, including 1304 diagnosed GDM cases, were analyzed. The meta-analysis showed that women in the low Vitamin C exposure group had higher odds of developing GDM (odds ratio 2.72, 95% CI:1.24-4.19). There was a greater likelihood of increased GDM risk with lower Vitamin C exposure (standardized mean difference: -0.71, 95% CI [-1.07 -0.36]). Subgroup analysis revealed that both internal and external Vitamin C exposure, along with exposure during the second or third trimester of pregnancy, was associated with higher GDM incidence rates under low Vitamin C exposure. Sensitivity analysis confirmed the robustness of the results, and no significant publication bias was detected. Low Vitamin C exposure during pregnancy may increase the risk of GDM. Given these findings, it could be beneficial for pregnant women to increase their intake of Vitamin C-rich foods and to ensure adequate blood Vitamin C levels as a preventive measure against GDM.