Increased Risk Of Gestational Diabetes Mellitus Research Articles

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

BackgroundPolycyclic 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. ObjectiveTo investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. MethodsThe 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. ResultsA 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. ConclusionsOur 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 with P ≤ 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.

Aromatic Amino Acids and Their Interactions with Gut Microbiota-Related Metabolites for Risk of Gestational Diabetes: A Prospective Nested Case-Control Study in a Chinese Cohort

Introduction: The aim of this study was to explore associations of aromatic amino acids (AAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high AAA and gut microbiota-related metabolites had interactive effects on GDM risk. Methods: We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women from 2010 to 2012. According to the International Association of Diabetes and Pregnancy Study Group’s criteria, 243 women were diagnosed with GDM. Binary conditional logistic regression was performed to examine associations of AAA with GDM risk. Interactions between AAA and gut microbiota-related metabolites for GDM were examined using additive interaction measures. Results: High phenylalanine and tryptophan were associated with increased GDM risk (OR: 1.72, 95% CI: 1.07–2.78 and 1.66, 1.02–2.71). The presence of high trimethylamine (TMA) markedly increased the OR of high phenylalanine alone up to 7.95 (2.79–22.71), while the presence of low glycoursodeoxycholic acid (GUDCA) markedly increased the OR of high tryptophan alone up to 22.88 (5.28–99.26), both with significant additive interactions. Furthermore, high lysophosphatidylcholines (LPC18:0) mediated both interactive effects. Conclusions: High phenylalanine may have an additive interaction with high TMA, while high tryptophan may have an additive interaction with low GUDCA toward increased risk of GDM, both being mediated via LPC18:0.

The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Maternal folate has been shown to relate to the risk of gestational diabetes mellitus (GDM). However, the existing studies have yielded inconsistent conclusions. The purpose of this study was to systematically review the association between maternal folate status and the risk of GDM. Observational studies up to 31 October 2022 were included. Study characteristics, the means and standard deviations (SDs) of folate levels (serum/red blood cell (RBC)), the odds ratios (ORs) with 95% confidence intervals (CIs) and the time for folate measurement were extracted. Compared with the non-GDM group, serum and RBC folate levels in women with GDM were significantly higher. Our subgroup analysis demonstrated that serum folate levels in the GDM group were significantly higher than in the non-GDM group only in the second trimester. RBC folate levels in the GDM group were significantly higher than in the non-GDM group in the first and second trimesters. Taking serum/RBC folate levels as continuous variables, the adjusted odds ratios of GDM risk showed that increased serum folate concentration rather than RBC folate elevated the risk of GDM. In the descriptive analysis, five studies reported high serum folate levels increased GDM risk, whereas the other five showed no association between serum folate levels and GDM risk. Moreover, the rest three studies pointed out high RBC folate levels increased GDM risk. Altogether we found that the risk of GDM is associated with high serum/plasma and RBC folate levels. Future studies should determine the recommended folic acid cutoff balancing the risk for GDM and fetal malformations.

Maternal hemoglobin change from early pregnancy to second trimester is associated with risk of gestational diabetes mellitus: a retrospective cohort study.

The accrual of iron that is reflected in high maternal hemoglobin (Hb) status is increasingly recognized as a risk factor for gestational diabetes mellitus (GDM). Changes in maternal Hb level could also implicate glycemic status in pregnancy. This study aimed to determine the associations between maternal Hb levels and their changes with GDM. In this retrospective cohort study, a total of 1,315 antenatal records of mothers with singleton pregnancies from eight health clinics of a district in the northern region of Peninsular Malaysia who delivered between 1st January 2016-31st December 2017 were analyzed. Data extracted from the records were socio-demographic, anthropometric, obstetrical, and clinical data. Hb levels were extracted at booking (<14 weeks) and second trimester (14-28 weeks). Change in Hb was determined by subtracting the Hb level in the second trimester from the booking Hb level and was categorized as decreased, unchanged, and increased Hb. The associations between maternal Hb levels and their changes with GDM risk were analyzed using multiple regression, adjusting for covariates in four different models. Model 1: maternal age and height. Model 2: covariates of Model 1 added with parity, history of GDM, and family history of diabetes. Model 3: covariates of Model 2 added with iron supplementation at booking. Model 4: covariates of Model 3 added with Hb level at booking. Unchanged Hb level from booking to second trimester was significantly associated with GDM risk in Model 1 (AOR: 2.55; 95% CI: 1.20, 5.44; p < 0.05), Model 2 (AOR: 2.45, 95% CI: 1.13, 5.34; p < 0.05) Model 3 (AOR: 2.42; 95% CI: 1.11, 5.27; p < 0.05), and Model 4 (AOR: 2.51; 95% CI: 1.15, 5.49; p < 0.05). No significant associations were observed between maternal Hb levels and GDM in the study. Unchanged Hb levels from the booking (<14 weeks of gestation) to the second trimester (14-28 weeks) increased GDM risk. Further investigation is warranted to evaluate the associations between changes in maternal Hb and GDM risk and to identify potential factors influencing this relationship.

Insulin Sensitivity and β-Cell Function During Early and Late Pregnancy in Women With and Without Gestational Diabetes Mellitus.

To evaluate the metabolic alterations associated with gestational diabetes mellitus (GDM) in women with overweight or obesity. We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrations, insulin sensitivity (IS; Matsuda index), and β-cell function (i.e., β-cell responsiveness to glucose) by using a frequently sampled oral glucose tolerance test (OGTT) at 15 and 35 weeks' gestation in women with overweight or obesity who had GDM (n = 29) or did not have GDM (No-GDM; n = 164) at 35 weeks. At 15 weeks, IS and β-cell function were lower, and fasting, 1-h, and total area-under-the-curve plasma glucose concentrations during the OGTT were higher (all P < 0.05) in the GDM than in the No-GDM group. At 35 weeks compared with 15 weeks, IS decreased, β-cell function increased, and postprandial suppression of plasma FFA was blunted in both the GDM and No-GDM groups, but the decrease in IS and the increase in postprandial FFA concentration were greater and the increase in β-cell function was less (all P ≤ 0.05) in the GDM than in the No-GDM group. A receiver operating characteristic curve analysis showed that both fasting plasma glucose and 1-h OGTT glucose concentration at 15 weeks are predictors of GDM, but the predictive power was <30%. Women with overweight or obesity and GDM, compared with those without GDM, have worse IS and β-cell function early during pregnancy and a greater subsequent decline in IS and blunted increase in β-cell function. Increased fasting and 1-h OGTT plasma glucose concentration early during pregnancy are markers of increased GDM risk, albeit with weak predictive power.

Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population.

MiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM). A total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level. There were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes. Our findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.

Early pregnancy particulate matter exposure, pre-pregnancy adiposity and risk of gestational diabetes mellitus in Finnish primiparous women: An observational cohort study

AimsTo evaluate the association between the exposure of particulate matter with an aerodynamic diameter of ≤ 2.5μm (PM2.5) and with an aerodynamic diameter of ≤ 10μm (PM10) over the first trimester and the risk of gestational diabetes mellitus (GDM), and to assess whether maternal pre-pregnancy body mass index (BMI) modified the GDM risk. MethodsAll Finnish primiparous women without previously diagnosed diabetes who delivered between 2009 and 2015 in the city of Vantaa, Finland, composed the study cohort (N = 6189). Diagnosis of GDM was based on a standard 75 g 2-hour oral glucose tolerance test. The average daily concentration of PM2.5 and PM10 over the first trimester was calculated individually for each woman. The relationship between exposure of PM2.5 and PM10 and GDM was analyzed with logistic models. ResultsNo association was observed between the average daily concentrations of PM2.5 and PM10 over the first trimester and the GDM risk. When simultaneously taking BMI and PM10 into account both mean daily PM10 concentration (p = 0.047) and pre-pregnancy BMI (p = 0.016) increased GDM risk independently and an interaction (p = 0.013) was observed between PM10 concentration and pre-pregnancy BMI. ConclusionsEven globally low PM10 exposure level together with elevated maternal pre-pregnancy BMI seems to increase the GDM risk.

The Association between Maternal B Vitamins in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study.

Background: This study evaluated the association between maternal B vitamins in early pregnancy and gestational diabetes mellitus (GDM) risk. Methods: A cohort of 1265 pregnant women was recruited at 8−15 weeks of gestation in 2021−2022 (Shanghai, China). Pregnancies with both serum B vitamin measurements at recruitment and glucose measurements at 24−28 weeks of gestation were included in the final analysis. Results: Of the 1065 pregnancies, in the final analysis, GDM occurred in 121 women (11.36%). In multivariate logistic models, an increased risk trend across serum vitamin B1 quartiles with GDM was observed (p-Trend = 0.001). Compared with women in the lowest quartile of serum vitamin B6, those in the upper two quartiles had approximately twofold higher odds of GDM. Moreover, compared with women with vitamin B12 levels < 150 pmol/L, those with vitamin B12 levels > 150 pmol/L had lower odds of GDM (p = 0.005). The restricted cubic spline regression models also revealed that serum vitamin B6 and vitamin B12 were associated with an increased risk of GDM in a nonlinear fashion. Conclusions: Our study shows that higher maternal serum vitamin B1 and B6 levels in early pregnancy are associated with increased GDM risk, while sufficient vitamin B12 status is associated with lower GDM risk.

Peri-conceptional exposure to ambient air pollution increases risk of gestational diabetes among pregnant participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study

Background: Exposures to air pollution potentially disrupt maternal metabolic adaptation during pregnancy. However, influences of preconception and prenatal exposures to ambient air pollution on gestational diabetes mellitus (GDM) remain unclear, and even less is known about sensitive windows for these exposures’ effect on GDM. Methods: In 617 pregnant participants enrolled the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we estimated daily levels of ambient particulate matter (PM₁₀; PM₂.₅), nitrogen dioxide (NO₂), ozone (O₃) using spatial interpolation. GDM was ascertained from medical records by physician diagnosis or defined as abnormally high glucose challenge and tolerance test results. We used distributed lag models (DLM) with Poisson regression to identify sensitive exposure windows by estimating weekly associations of exposures from pre-conception week (PcW) 12 to gestational week (GW) 24 with GDM risk, adjusting for maternal and meteorological factors. Analyses were additionally stratified by median prenatal Perceived Stress Scale (PSS, 14), median pre-pregnancy body mass index (BMI, 27.5 kg/m²), median age (28 years), and newborn sex to explore differential susceptibility to exposure effects. Results: Sixty (9.7%) participants were diagnosed with GDM. We identified sensitive peri-conceptional exposure windows for PM₂.₅, PM₁₀, and NO₂ ranging from PcW5 to GW3 associated with increased GDM risk. An IQR increase in each pollutant was associated with 5% (95%CI: 3.3-6.7%), 6% (5.9-7.4%), and 11% (9.3-12.2%) increased GDM risk, respectively. In stratified analyses, effects of PM₁₀ and NO₂ in the identified sensitive windows were greater among those &amp;#x2265;28 years old, with BMI&amp;#x2265;27.5 kg/m², or with PSS&amp;#x2265;14. Conclusions: Peri-conception exposures to ambient air pollutants were associated with increased risk of GDM. Stronger effects in the identified sensitive windows were seen in participants who were older, had higher BMI, or higher perceived stress. Keywords: air pollution, gestational diabetes, sensitive window, susceptibility, perceived stress, preconception

Association of ambient fine particulate matter exposure with gestational diabetes mellitus and blood glucose levels during pregnancy

BackgroundPrevious studies have examined the associations between ambient fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM). However, limited studies explored the relationships between PM2.5 exposure and blood glucose levels during pregnancy, especially in highly polluted areas. ObjectivesTo examine the associations of prenatal ambient PM2.5 exposure with GDM and blood glucose levels, and to identify the sensitive exposure windows in a highly air-polluted area. MethodsFrom July 2016 to October 2017, a birth cohort study was conducted in Beijing, China. Participants were interviewed in each trimester regarding demographics, lifestyle, living and working environment, and medical conditions. Participant's daily ambient PM2.5 levels from 3 m before last menstrual period (LMP) to the third trimester was estimated by a hybrid spatiotemporal model. Indoor air quality index was calculated based on environmental tobacco smoke, ventilation, cooking, painting, pesticide, and herbicide use. Distributed lag non-linear model was applied to explore the sensitive weeks of PM2.5 exposure. ResultsOf 165 pregnant women, 23 (13.94%) developed GDM. After adjusting for potential confounders, PM2.5 exposure during the 1st trimester was associated with higher odds of GDM (10 μg/m3 increase: OR = 1.89, 95% CI: 1.04–3.49). Each 10 μg/m3 increase in PM2.5 during the 2nd trimester was associated with 17.70% (2.21–33.20), 15.99% (2.96–29.01), 18.82% (4.11–33.52), and 17.10% (3.28–30.92) increase in 1-h, 2-h, Δ1h-fasting (1-h minus fasting), and Δ2h-fasting (2-h minus fasting) blood glucose levels, respectively. PM2.5 exposure at 24th-27th weeks after LMP was associated with increased GDM risk. We identified sensitive exposure windows of 21st-24th weeks for higher 1-h and 2-h blood glucose levels and of 20th-22nd weeks for increased Δ1h-fasting and Δ2h-fasting. ConclusionsAmbient PM2.5 exposure during the second trimester was associated with higher odds of GDM and higher blood glucose levels. Avoiding exposure to high air pollution levels during the sensitive windows might prevent women from developing GDM.