Higher Risk Of Gestational Diabetes Mellitus Research Articles

Gestational Diabetes Prevalence Estimates from Three Data Sources, 2018.

We investigated 2018 gestational diabetes mellitus (GDM) prevalence estimates in three surveillance systems (National Vital Statistics System, State Inpatient Database, and Pregnancy Risk Assessment Monitoring Survey). We calculated GDM prevalence for jurisdictions represented in each system; a subset of data was analyzed for people 18-39 years old in 22 jurisdictions present in all three systems to observe dataset-specific demographics and GDM prevalence using comparable categories. GDM prevalence estimates varied widely by data system and within the data subset despite comparable demographics. Understanding the differences between GDM surveillance data systems can help researchers better identify people and places at higher risk of GDM.

Association of BDNF polymorphism with gestational diabetes mellitus risk: a novel insight into genetic predisposition.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy with potential long-term health implications for the mother and child. The interplay between genetics and GDM susceptibility remains an area of active research. Recently, brain-derived neurotrophic factor (BDNF) was investigated in relation to obesity and impaired glucose metabolism and pathogenesis. We aimed to investigate the association of common BDNF polymorphisms, with GDM risk in Israeli females. A cohort of 4,025 Israeli women data for BDNF common SNPs was analyzed for potential association with GDM using binary logistic regressions analysis (SPSS 29.0 and R) adjusted for confounding variables (age, T1DM, T2DM, PCOS) under different genetic models. The GDM and Non-GDM genetic frequencies for the BDNF rs925946 Tag-SNP were significantly different. The genetic frequencies were 54.16 %, and 66.91 % for the wild type (GG), 38.88 and 29.64 % for the heterozygotes (TC), and 6.94 and 3.48 % for the risk allele homozygotes (TT) for the GDM non-GDM populations, respectively. Carriers of BDNF rs925946 were significantly associated with higher risk for GDM, following the dominant genetic model (OR=1.7, 95 % CI 1.21-2.39, p=0.002), the recessive genetic model (OR=2.05, 95 % CI 1.04-4.03, p=0.03), and the additive genetic model (OR=1.62, 95 % CI 1.13-2.3, p=0.008). This association persisted after adjusting for age, T1DM, T2DM, and polycystic ovary syndrome (PCOS). Carrying BDNF rs925946 polymorphism predisposes to a higher risk of GDM pathogenesis. Its role and implications warrant further investigation, especially when considering preventive measures for GDM development.

Dietary fat intake with risk of gestational diabetes mellitus and preeclampsia: a systematic review and meta-analysis of prospective cohort studies.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are commonly observed medical complications in pregnancy. Dietary total fat and fatty acids associated with GDM and PE risk have been examined in several epidemiological studies. In some instances, systematic reviews and meta-analyses might provide more accurate dietary recommendations. This systematic review and dose-response meta-analysis was conducted to investigate the association between dietary total fat and fatty acids and the risk of GDM and PE. Research on dietary fat intake and the risk of GDM and PE was conducted through systematic searches of the PubMed, Scopus, and Web of Science databases for articles published up to August 19, 2023. An investigation of associations between dietary intake of total fat and fatty acids and the risk of GDM and PE was performed using prospective cohort study designs. Twenty-one prospective cohort studies were considered eligible. Findings indicated that higher intakes of total fat (relative risk [RR], 1.08; 95% confidence interval [CI], 1.02-1.14), animal fat (RR, 1.56; 95%CI, 1.34-1.89), vegetable fat (RR, 1.23; 95%CI, 1.05-1.45), dietary cholesterol (RR, 1.48; 95%CI, 1.10-2.00), and omega-3 fatty acid (RR, 1.11; 95%CI, 1.02-1.20) are associated with a greater risk of GDM. However, no significant association was found between dietary total fat and fatty acids and the risk of PE. Dose-response meta-analyses suggested every 10% increment in total energy intake from total fat, 5% from animal fat, 5% from vegetable fat, and 100 mg from cholesterol was related to 15%, 12%, 7%, 14%, and 20% higher GDM risk, respectively. Overall, total fat, animal fat, vegetable fat, dietary cholesterol, and omega-3 fatty acid consumption are associated with a small but statistically significant increase in GDM risk. PROSPERO (CRD42023466844).

Abstract 68: The Association of Pre-Pregnancy Body Mass Index With Gestational Diabetes Across Maternal Race and Ethnicity Subgroups

Objective: Gestational diabetes mellitus (GDM) complicates 5-11% of pregnancies within the US and maternal obesity is a strong risk factor. Asian individuals are known to have a higher risk of GDM at a lower body mass index (BMI) compared to European populations. However, Asian Americans represent a heterogenous group, and no studies have captured the variation between BMI and GDM across racial groups at a national level. Our objective was to characterize differences in the association between BMI and GDM by maternal race/ethnicity with a specific focus on Asian subgroups. Methods: We used data from the National Vital Statistics System natality files from 2016 to 2019, capturing all live births in the US, to ascertain incidence of GDM. We used logistic regression with BMI modeled as a cubic b-spline to model the association with risk (predicted probability) of GDM. All analyses were stratified by maternal race/ethnic group. Results: Of the eligible 13.3M pregnancies resulting in live births, 6.5% were affected by GDM, ranging from 5.2% among non-Hispanic Black individuals to 12.3% among Asian individuals. The incidence of GDM was highest among women with obesity with rates of 20.3% in Asian individuals, and 16.0% in American Indian and Alaska Native individuals with obesity (Figure 1A). At a BMI of 23 kg/m2 the predicted probability of GDM was 6.5% for Asian individuals compared to 2.3% for non-Hispanic Black individuals (Figure 1B). There was substantial heterogeneity across Asian ancestry subgroups between pre-pregnancy obesity and GDM incidence (Figure 1C), with Vietnamese and Korean individuals having the largest increase in risk with higher pre-pregnancy BMI (Figure 1D). Conclusion: The risk of GDM increased with higher pre-pregnancy BMI across all maternal race/ethnicity groups, but risk was higher for Asian Americans at a lower BMI. There was substantial variation in BMI-related risk of GDM across Asian ancestry subgroups, suggesting need for more tailored screening and intervention strategies for GDM.

A systematic review and meta-analysis of the association between exposure to potentially toxic elements and gestational diabetes mellitus

Potentially toxic elements (PTEs), including heavy metal exposures, have been associated with numerous negative pregnancy and birth outcomes. However, the association between PTE exposure and gestational diabetes mellitus (GDM) has not yet undergone a comprehensive systematic review. Consequently, this study undertook the first-ever systematic review and meta-analysis of observational studies concerning this association. All relevant articles published in English were searched in Scopus, PubMed, and Web of Science until November 6, 2023, adhering to the MOOSE guidelines. The quality of retrieved studies was evaluated based on the Gascon et al. method. The meta-analysis of association estimates was performed using random effects meta-analysis. Egger’s regression was employed to evaluate publication bias. In total, 16 articles (n = 116,728 participants) were included in our review, with 11 eligible for meta-analysis. Quality assessment categorized five studies (31%) as excellent, nine studies (56%) as good, and two studies (13%) as fair. Maternal high levels of Hg during pregnancy were associated with an increased risk of GDM (for each one-quartile increase in Hg: 1.20, 95% CI 1.08, 1.31), while serum Cd levels during the second trimester were associated with a lower risk of GDM (for each one-quartile increase in Cd: 0.76, 95% CI 0.65, 0.87). Furthermore, exposure to Pb was not associated with higher risk of GDM. In summary, our comprehensive review and meta-analysis underscore the possible negative influence of Hg exposure on GDM.

Assisted reproductive technology and physical activity among Chinese pregnant women at high risk for gestational diabetes mellitus in early pregnancy: A cross-sectional study.

Currently, the number of pregnant women at high risk for gestational diabetes mellitus (GDM) and using assisted reproductive technology (ART) is increasing. The present study aims to explore the relationship between ART and physical activity in Chinese pregnant women at high risk for GDM in early pregnancy. A cross-sectional study was conducted in a regional teaching hospital in Guangzhou, China, between July 2022 and March 2023. Three hundred fifty-five pregnant women at high risk for GDM in early pregnancy completed the Chinese version of the Pregnant Physical Activity Questionnaire (PPAQ), the Pregnancy Physical Activity Knowledge Scale, the Pregnancy Physical Activity Self-Efficacy Scale, the Pregnancy Physical Activity Social Support Scale, and a sociodemographic and obstetric characteristics data sheet. Compared to women who conceived naturally, women who used ART were more likely to be 35 years or older, unemployed, primigravidae, and to have intentionally planned their pregnancies. Women who used ART had significantly lower levels of physical activity and self-efficacy compared to their counterparts who conceived naturally. Over half (55.6%) of women who used ART reported being physically inactive, and those with lower self-efficacy, as well as the unemployed, were significantly more likely to be inactive. Physical inactivity is a critical clinical issue among women who use ART, especially in the context of GDM risk. Future research should develop and test physical activity programs, including enhancing physical activity self-efficacy for women who use ART. Patient or public contribution: In this study, survey questionnaires were completed by participants among Chinese pregnant women at high risk for GDM in early pregnancy.

Factors Associated with Knowledge about Gestational Diabetes Mellitus among Women Attending Antenatal Clinics in Riyadh, Saudi Arabia

Abstract Background: Gestational diabetes mellitus (GDM) is an increasing public health problem worldwide. Measuring the level of knowledge in a population at high risk for GDM will highlight the gaps and help in designing appropriate interventions. The objective of this study was to measure the knowledge about GDM and to identify the factors associated with it among pregnant women in Riyadh city, Saudi Arabia. Methodology: A cross-sectional study was conducted with pregnant women seeking antenatal care services in two of the public sector tertiary care hospitals in Riyadh city. The study was performed using a self-administrated predesigned questionnaire. Collected data were analyzed using SPSS program. Results: More than 40% of the participants had poor knowledge about GDM complications, diagnosis and management. Women with lack of exercise [adjusted odds ratio 3.3 (95% CI 1.8, 6.1)]; having past histroy of GDM [3.2 (1.8, 5.7); primigravida [2.9 (1.6, 5.1)]; information on GDM received from doctors [2.0 (1.2, 3.4)] and those with low education level [1.8 (1.1, 2.9)] were more likely to have poor knowledge about GDM. Whereas, women with positive family history were 60 times more likely to have good knowledge about GDM. Conclusion: Primigravida mothers and those with low education level should receive specific information and awareness regarding GDM. Healthy lifestyle is important for the prevention and improvement in the diagnosis and management of GDM among pregnant women in Riyadh.

A Healthy, Low-Carbohydrate Diet During Pregnancy Is Associated With a Reduced Risk of Gestational Diabetes Mellitus.

Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study

BackgroundPrevious evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women.MethodsThe study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records.ResultsThe mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001–0.028).ConclusionHigher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Childhood adversity and the risk of gestational diabetes: A population-based cohort study of nulliparous pregnant women.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, and though it may be linked to childhood adversity, the effect of different types of adversity remains unclear. Childhood adversity is linked to a younger maternal age, which may hide the overall impact of adversity on GDM risk. We therefore aimed to explore the association between different types of childhood adversity and GDM while accounting for the potential impact of maternal age. We used Danish nation-wide register data, including 208,207 women giving birth for the first time from 2004-2018. Five adversity groups were used to examine the effect of childhood adversity on GDM risk: 1) low (referent group), 2) early life material deprivation, 3) persistent deprivation, 4) loss or threat of loss within the family, and 5) high adversity. 5375 women were diagnosed with GDM in the study population (2.6% absolute risk). Compared to women who experienced low adversity, the other adversity groups had a higher GDM risk (absolute difference (%)) directly; early material deprivation [0.64% (95% CI 0.44;0.84)], persistent deprivation [0.63% (0.41;0.86)], loss or threat of loss [0.73% (0.42;1.05)] and high adversity [0.80% (0.32;1.27)]. The indirect effect of maternal age attenuated the total effect of childhood adversity on GDM by an absolute difference of 0.25-0.46%. Experiencing childhood adversity to any extent is associated with a higher risk of GDM. Interventions aimed at preventing childhood adversity may have a positive effect in reducing GDM burden and the associated health risks.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Pregnant Chinese Women.

This study aimed to develop a simplified screening model to identify pregnant Chinese women at risk of gestational diabetes mellitus (GDM) in the first trimester. This prospective study included 1289 pregnant women in their first trimester (6-12weeks of gestation) with clinical parameters and laboratory data. Logistic regression was performed to extract coefficients and select predictors. The performance of the prediction model was assessed in terms of discrimination and calibration. Internal validation was performed through bootstrapping (1000 random samples). The prevalence of GDM in our study cohort was 21.1%. Maternal age, prepregnancy body mass index (BMI), a family history of diabetes, fasting blood glucose levels, the alanine transaminase to aspartate aminotransferase ratio (ALT/AST), and the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were selected for inclusion in the prediction model. The Hosmer-Lemeshow goodness-of-fit test showed good consistency between prediction and actual observation, and bootstrapping indicated good internal performance. The area under the receiver operating characteristic curve (ROC-AUC) of the multivariate logistic regression model and the simplified clinical screening model was 0.825 (95% confidence interval [CI] 0.797-0.853, P < 0.001) and 0.784 (95% CI 0.750-0.818, P < 0.001), respectively. The performance of our prediction model was superior to that of three other published models. We developed a simplified clinical screening model for predicting the risk of GDM in pregnant Chinese women. The model provides a feasible and convenient protocol to identify women at high risk of GDM in early pregnancy. Further validations are needed to evaluate the performance of the model in other populations. ClinicalTrials.gov identifier: NCT03246295.

Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort

BackgroundDiet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. ObjectivesThe aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. MethodsThis study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. ResultsSe and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006). ConclusionsLow serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.

Development and validation of a clinical model to predict preconception risk of gestational diabetes mellitus in nulliparous women: A retrospective cohort study.

To develop and validate a model to predict the preconception risk of gestational diabetes mellitus (GDM) in nulliparous women. This was a retrospective cohort study. A total of 1565 women in early pregnancy who underwent preconception health examinations in the Women and Children's Hospital of Chongqing Medical University between January 2020 and June 2021 were invited to participate in a questionnaire survey. Logistic regression analysis was performed to determine the preconception risk factors for GDM. These factors were used to construct a model to predict GDM risk in nulliparous women. Then, the model was used to assess the preconception risk of GDM in 1060 nulliparous women. Independent preconception risk factors for GDM included the following: age 35 years or greater, diastolic blood pressure 80 mm Hg or greater, fasting plasma glucose 5.1 mmol/L or greater, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) 24 or greater, weight gain 10 kg or greater in the year before pregnancy, age of menarche 15 years or greater, three or more previous pregnancies, daily staple food intake 300 g or greater, fondness for sweets, and family history of diabetes. BMI less than 18.5, daily physical activity duration 1 h or greater, and high-intensity physical activity were protective factors. These factors were used to construct a model to predict GDM risk in nulliparous women, and the incidence of GDM significantly increased as the risk score increased. The area under the curve of the prediction model was 0.82 (95% confidence interval 0.80-0.85). The preconception GDM risk prediction model demonstrated good predictive efficacy and can be used to identify populations at high risk of GDM before pregnancy, which provides the possibility for preconception intervention.

The Association Between the Imbalance of Single-Carbon Nutrients in Early Pregnancy and Gestational Diabetes Mellitus Risk is Influenced by Serum Selenium Status: A Cohort Study.

The role of imbalanced one-carbon nutrients in gestational diabetes mellitus (GDM) risk has garnered significant interest, yet existing studies yield inconsistent results. Our objective was to assess whether the association between an unbalanced ratio of folate to vitamin B12 and GDM risk is influenced by the status of other micronutrients. This cohort study included 366 singleton-pregnancy Han women enrolled at the Shunyi District Maternal and Child Health Hospital in Beijing, China. During the first trimester of pregnancy, we measured red blood cell (RBC) folate, serum levels of vitamin B12, vitamin D, and selenium. We examined the association between the imbalanced status of RBC folate and vitamin B12 and GDM risk using logistic regression, stratified by serum selenium or vitamin D status. Among the 366 women, 67 (18.3%) were diagnosed with GDM, 201 (54.9%) had vitamin D deficiency, and 245 (66.9%) had selenium deficiency. Overall, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly higher risk of GDM compared to those in reference tertile (all P > 0.05). Subsequently, we divided women into deficient and non-deficient groups based on serum selenium or vitamin D levels. In women with selenium deficiency, those in the highest tertile of the RBC folate/vitamin B12 ratio had the highest odds of GDM [OR: 3.40 (1.16-9.97), P=0.026] after adjusting for covariates. However, similar findings were not observed in pregnancies with normal selenium status. Irrespective of vitamin D status, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly increased risk of GDM. Micronutrient deficiencies are common in early pregnancy. Women with a higher folate/vitamin B12 ratio coupled with selenium deficiency in early pregnancy have a higher GDM risk. These findings underscore the importance of micronutrient assessment in early pregnancy and subsequent interventions for micronutrient deficiencies.

Myoinositols Prevent Gestational Diabetes Mellitus and Related Complications: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to prevent GDM. The present systematic review and meta-analysis aimed to investigate the effect of inositol supplementation in preventing GDM and related outcomes. Systematic search was performed in CENTRAL, MEDLINE, and Embase until 13 September 2023. Eligible randomized controlled trials (RCTs) compared the efficacy of inositols to placebo in pregnant women at high risk for GDM. Our primary outcome was the incidence of GDM, whereas secondary outcomes were oral glucose tolerance test (OGTT) and maternal and fetal complications. (PROSPERO registration number: CRD42021284939). Eight eligible RCTs were identified, including the data of 1795 patients. The incidence of GDM was halved by inositols compared to placebo (RR = 0.42, CI: 0.26-0.67). Fasting, 1-h, and 2-h OGTT glucose levels were significantly decreased by inositols. The stereoisomer myoinositol also reduced the risk of insulin need (RR = 0.29, CI: 0.13-0.68), preeclampsia or gestational hypertension (RR = 0.38, CI: 0.2-0.71), preterm birth (RR = 0.44, CI: 0.22-0.88), and neonatal hypoglycemia (RR = 0.12, CI: 0.03-0.55). Myoinositol decrease the incidence of GDM in pregnancies high-risk for GDM. Moreover, myoinositol supplementation reduces the risk of insulin need, preeclampsia or gestational hypertension, preterm birth, and neonatal hypoglycemia. Based on the present study 2-4 g myoinositol canbe suggested from the first trimester to prevent GDM and related outcomes.

Development and feasibility of a theory-guided and evidence-based physical activity intervention in pregnant women with high risk for gestational diabetes mellitus: a pilot clinical trial

BackgroundPhysical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM.MethodsThe study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention.ResultsThe validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful.ConclusionsThe developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study.Trial registrationThe study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR).

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.

Target Exposome for Characterizing Early Gestational Exposure to Contaminants of Emerging Concern and Association with Gestational Diabetes Mellitus.

Characterization of gestational exposure to complex contaminants of emerging concern (CECs) is critical to the identification of environmental risk factors for pregnancy complications. However, determination of various CECs with diverse physicochemical properties in biological fluids is technically challenging. In the present study, we developed a target exposome protocol, consisting of simple liquid-liquid extraction-based sample preparation and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, to determine 325 CECs covering 11 subclasses, including poly- and perfluoroalkyl substances, organophosphate esters, ultraviolet (UV) stabilizers, synthetic antioxidants, phthalate esters, and several others. The protocol exhibits exceptional advantages over traditional approaches in the coverage of chemicals, sample volume demand, and time and financial cost. The protocol was applied in a prospective nested gestational diabetes mellitus (GDM) study including 120 cases and 240 matched healthy controls. Thirty-three CECs were detected in >70% of the samples, with a combined concentration of 17.0-484.7 ng/mL. Bayesian kernel machine regression analysis showed that exposure to the CEC mixture was significantly associated with a higher GDM risk. For example, when increasing all CECs in the mixture from 50th percentile to 75th percentile, the estimated probit of GDM incidence had an increase of 92% (95% CI: 56%, 127%). Meanwhile, perfluorohexanesulfonic acid, 1,3-diphenylguanidine, and dibutyl fumarate were identified as the key CECs driving the joint effect. This work demonstrates great potential of our target exposome protocol for environmental risk factor identification in large-scale epidemiology or biomonitoring studies.

Pregnancy Cholesterol Metabolism Markers and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study.

This study aims to determine the association of pregnancy cholesterol metabolism markers with gestational diabetes mellitus (GDM) risk. We performed a nested case-control study in the Tongji Birth Cohort. GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Nine cholesterol metabolism markers were detected using gas chromatography-mass spectrometry. Conditional logistic regression models were conducted. A total of 444 pregnant women were matched in a 1:2 ratio. The cholestanolTC and β-sitosterolTC in cholesterol absorption markers presented negative associations with the risks of GDM (adjusted OR: 0.77, 95% CI: 0.61-0.96; adjusted OR: 0.80, 95% CI: 0.64-1.00). The desmosterolTC in cholesterol synthesis markers were positively associated with the risks of GDM (adjusted OR: 1.25, 95% CI: 1.00-1.56), similar in the ratios of cholesterol synthesis to absorption markers. After adjustment for insulin or HOMA-IR, these effects were reduced. In conclusion, higher cholesterol synthesis and lower cholesterol absorption marker levels in the first pregnancy are associated with a higher risk of GDM, and insulin resistance may play a vital role in this association.

Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. Serum FGF21 levels were measured at 6-15weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction=0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24kg/m2 ) and FGF21 levels (≥median and <median), a significant association was observed in those with higher BMI and FGF21 levels (odds ratio, 2.12; 95% CI: 1.41, 3.20) but not in those with either higher BMI or higher FGF21, with a significant additive interaction (relative excess risk due to interaction=1.23; 95% CI: 0.27, 2.20). FGF21 was also correlated with unfavourable glucose and lipid biomarkers as well as adipokines. Elevated serum FGF21 levels in early pregnancy were associated with a higher risk of GDM, particularly among those with overweight/obesity.