To investigate the association of serum N,N,N-trimethyl-5-aminovaleric acid (TMAVA), trimethylamine N-oxide (TMAO), and trimethyllysine (TML) levels with gestational diabetes mellitus (GDM).

Seventy pregnant women from the Hunan Provincial Maternal and Child Health Care Hospital (March 2021 to October 2023) were enrolled in this study. Forty GDM patients with GDM were included in the GDM group (GDM), and 30 healthy controls were included (Con). Participants were further categorized into adverse and good outcome groups based on pregnancy outcomes. Serum TMAVA, TMAO, and TML levels were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Correlations between biomarker levels and clinical indicators were assessed using Pearson and Spearman analyses. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate risk factors and predictive value.

Serum TMAVA, TMAO, and TML levels were significantly higher in the GDM group. TMAVA levels were positively correlated with fasting plasma glucose (FPG), fasting insulin (FINS), creatinine (Cr), TMAO, and TML. TMAO and TML positively correlated with FPG, 2-h postprandial glucose (2h PG), FINS, Cr, and uric acid (UA) levels, while TMAO negatively correlated with triglyceride (TG). Combined TMAVA, TMAO, and TML predicted GDM with an area under the curve (AUC) of 0.940 (95% CI: 0.883-0.997). Elevated TMAVA levels were associated with adverse pregnancy outcomes in GDM, with an AUC of 0.757 (95% CI: 0.612-0.902).

Elevated serum levels of TMAVA, TMAO, and TML were significantly associated with the occurrence of GDM and adverse pregnancy outcomes. The combined detection of these three biomarkers demonstrated superior accuracy in predicting GDM. Among them, TMAVA demonstrated the highest predictive efficiency for adverse pregnancy outcomes in women with GDM. These findings provide new biomarkers for early screening and risk assessment of GDM, offering promising applications in clinical practice.

Gestational diabetes mellitus (GDM) increases adverse neonatal and maternal outcomes. Understanding the prevalence and risk factors of GDM is necessary to plan health care interventions and policy.

To determine the prevalence and risk factors of GDM in Thai Binh, Vietnam.

A cross-sectional study was conducted in two health facilities in Thai Binh, Vietnam, with the participation of 1,106 pregnant women. Women were recruited at their first antenatal care visit where face-to-face interviews about socioeconomic and reproductive factors were performed. A 2-hour 75 g oral glucose tolerance test was conducted at 24-28 weeks of gestation. GDM was diagnosed according to the World Health Organization 2013 criteria. Logistic regression analyses were used to assess the factors associated with GDM.

The prevalence rate of GDM was 27.1%. Multivariate logistic regression analysis showed maternal age from 25 to 34 (adjusted OR 2.0; 95%CI 1.3-2.9), maternal age ≥ 35 (adjusted OR 3.0; 95%CI 1.7-5.4), pregestational body mass index ≥ 23 (adjusted OR 1.6; 95%CI 1.1-2.3), family history of diabetes (adjusted OR 1.9; 95%CI 1.3-2.9), fertility treatment (adjusted OR 2.3; 95%CI 1.3-3.8), and previous GDM (adjusted OR 3.1; 95%CI 1.4-6.9) were associated with increased odds of GDM.

More than one-fourth of pregnant women in Thai Binh, Vietnam, may have GDM. Advanced maternal age, high pregestational body mass index, family history of diabetes, and previous GDM were associated with increased risk of GDM. Additionally, fertility treatment appears to be strongly associated with an increased risk of GDM.

This study aims to explore the distribution characteristics of oral microbiota in pregnant women with gestational diabetes mellitus (GDM) and its association with periodontitis.

This case-control study included 80 GDM women, divided into the periodontitis group (PD group, n = 40) and the periodontally healthy group (N group, n = 40). Unstimulated saliva samples were collected for 16S rRNA sequencing targeting the V3∼V4 region. We used α-diversity and β-diversity to assess the richness and diversity of the oral microbiota and the variability between groups. The Mann-Whitney U test and linear discriminant analysis effect size (LEfSe) analysis were used to identify significant differences in microbial composition and to evaluate categorical differences between groups.

Significant differences in α-diversity and β-diversity were observed between the PD group and the N group. The PD group exhibited a higher abundance of Bacteroidota, Fusobacteriota, Spirochaetota, Synergistota, and Choroflexi compared to the N group. LEfSe analysis identified Spirochaetora and Tetraptera as the taxonomic biomarkers in the PD group. Furthermore, activating environmental adaptation, terpenoid and polyketide metabolism, and the immune and endocrine systems pathways may be involved in the potential mechanisms of the PD group.

A significant correlation was observed between oral microbiota composition and periodontitis in pregnant women with GDM. Spirochaetota and Tetraptera are closely linked to the progression of periodontitis and may serve as biomarkers for early diagnosis. Targeting these microbial taxa could provide new strategies for preventing and managing periodontitis during pregnancy, potentially reducing adverse maternal and fetal outcomes.

Background: Hypovitaminosis D has become a warning sign for the development of gestational diabetes mellitus (GDM) with a lack of evidence related to pregnant mothers in Sri Lanka. Aim: This study was designed to compare serum 25(OH)D levels and selected biochemical parameters among a group of pregnant mothers in Sri Lanka. Methods: A total of 172 pregnant mothers (GDM-86 and non-GDM-86) were recruited to this case-control study from prenatal clinics at Colombo South Teaching Hospital, Sri Lanka. Serum 25(OH)D, fasting plasma glucose (FPG) and fasting serum insulin (FSI) were measured using overnight maternal fasting venous blood samples. Serum 25(OH)D level < 20 ng/mL was considered as "hypovitaminosis D". SPSS version 23.0 was used in data analysis. Results: During pregnancy, 44.2% (n = 38) of GDM and 38.4% (n = 33) of non-GDM mothers had received vitamin D supplements. Mean serum 25(OH)D concentrations between GDM and non-GDM mothers were 15.5 ± 4.5 ng/mL and 19.4 ± 5.9 ng/mL, respectively (P < 0.05). Among the participants, 84.9% of GDM and 60.5% of non-GDM mothers had serum 25(OH)D level < 20 ng/mL. FPG and HOMA-IR of GDM mothers were negatively correlated with serum 25(OH)D level (P < 0.05). Hypovitaminosis D was significantly associated with developing GDM after adjusting for family history of type 2 diabetes mellitus, maternal employment status, history of GDM, FPG, GWG at 24-28 weeks and HOMA-IR (aOR = 2.49; 95% CI: 1.083-5.762; P = 0.032). Conclusion: Future randomized controlled trials are recommended to determine whether adequate vitamin D supplementation can effectively reduce the incidence of developing GDM.

To evaluate whether diet and gestational diabetes mellitus (GDM) during pregnancy influence children's growth during their first 24 months.

Growth data of children (n = 378) of women with overweight/obesity were obtained from clinic records (birth, 3, 6, 12 and 24 months), and variables (standard deviation scores (SDS) or percentages) were calculated based on Finnish growth charts. Body composition was measured by air displacement plethysmography (n = 73, 24 months). Diet was assessed (diet quality index, nutrient intakes and diet inflammatory index (DII®)) in early and late pregnancy. GDM was determined by an oral glucose tolerance test.

A good dietary quality in early pregnancy associated positively with the children's height at each time point (adj. mean difference range = 0.28-0.30 SDS, p < 0.05) and head circumference at 12 and 24 months (adj. mean difference range = 0.38-0.42 SDS, p < 0.05). A good dietary quality in late pregnancy associated with a lower fat mass in children (adj. mean difference = -0.69, p < 0.05). A higher DII was correlated with a higher weight at 24 months but a reduced height at each time point (adj. p < 0.05). GDM associated negatively with the children's head circumference at birth and 6 months (adj. mean difference range = -0.43 to [-0.22] SDS, p < 0.05).

Consuming a good quality diet during pregnancy associated with a greater infantile height and head circumference but a lower adiposity in 2-year-old children. GDM may lead to a slightly smaller head circumference in early infancy. Mothers with overweight or obesity could support their children's growth by consuming a good quality diet, with low inflammatory potential during pregnancy.

ClinicalTrials.gov Identifier: NCT01922791, 14 August 2013.

To investigate the impact of hepatitis B virus carriers combined with gestational diabetes mellitus (HBVC & GDM) on pregnancy outcomes in a cohort of pregnant women from Hangzhou, China.

We set-up a retrospective cohort study to analyze data from 12,815 pregnant women who delivered in three Hangzhou tertiary hospitals between 2015 and 2022. Four groups were created according to the presence of HBV and/or GDM as follows: a non-HBVC & GDM group (n = 5,323), a HBVC group (n = 5,508), a GDM group (n = 919) and a HBVC & GDM group (n = 1,065). Univariate analysis was carried out with the Mann-Whitney U test or the chi-squared test; P < 0.05 was used as the screening criterion. Multivariate logistic regression analysis was then performed to investigate the effects of each of the relevant confounders on HBVC, GDM and HBVC & GDM. After adjusting for potential confounding variables, the results were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), with P < 0.05 considered as statistically significant.

The incidence of HBVC & GDM among pregnant women in Hangzhou, China was 0.96% (95% CI: 0.90-1.02%). The median maternal age of the pregnant women in the HBVC & GDM group was significantly higher than that in the HBVC, GDM and control groups (31.00 vs. 30.00, 30.00, 29.00, P < 0.001). The proportions of low birth weight (4.0% vs. 3.8%, 3.4%, 3.4%) and macrosomia (6.8% vs. 5.4%, 3.7%, 4.3%) in the HBVC & GDM group were significantly higher than in the other three groups, with significant differences between groups (P < 0.05). Multivariate logistic analysis revealed a progressive increase in risk values with increasing maternal age in the HBVC & GDM group (OR≥ 25&<30=1.632, OR≥ 30&<35=3.257, and OR≥ 35=5.611). In addition, the carriage risk of pregnant women over 35 years was approximately two-fold higher than that in the HBVC and GDM groups (5.611/2.251 and 5.611/3.130), respectively. The risk value increased progressively with increasing gravidity (OR2 = 1.364 and OR≥ 3=1.765). The risk of a floating population was as follows: Zhejiang-registered but non-Hangzhou (OR = 2.246) > outside Zhejiang Province (OR = 1.953) > Hangzhou-local (OR = 1). HBVC & GDM also increased the risk of intrahepatic cholestasis of pregnancy (ICP) (OR = 3.143, 95% CI: 2.223-4.445), pre-eclampsia (PE) (OR = 2.017, 95%CI: 1.315-3.095), macrosomia (OR = 1.548, 95% CI: 1.161-2.064), assisted vaginal delivery (OR = 1.501, 95% CI: 1.185-1.901) and Caesarean section (OR = 1.258, 95% CI: 1.035-1.528). HBVC & GDM also reduced the chance of delayed labor (gestational age > 41 week, OR = 0.217, 95% CI: 0.126-0.374).

The incidence rates of HBVC and GDM among pregnant women in Hangzhou City are relatively high. When HBVC & GDM co-existed, the risks of ICP, PE and macrosomia increased significantly. The risk of HBVC & GDM tended to increase progressively with increasing maternal age and increasing gravidity. For pregnant women of advanced age, those with increasing gravidity or those in a floating population, it is important to enhance educational awareness related to HBV, GDM, and especially HBVC & GDM in order to provide personalized antenatal medical care and reduce the risk of adverse pregnancy outcomes.

Gestational diabetes is a type of diabetes that develops during pregnancy and increases the risk of developing type 2 diabetes later in life. The rising prevalence of gestational diabetes mellitus (GDM) highlights the need for more comprehensive treatment strategies, with a particular emphasis on supporting maternal self-management. We showed recently that a mobile app, eMOM, where glucose, nutrition, and physical activity are combined within a single app, significantly improves multiple clinical outcomes among persons with gestational diabetes.

This study aims to explore the effects of the eMOM on maternal self-discovery and learning, autonomous motivation to manage GDM, and psychological well-being. Additionally, we examine the correlation between improved maternal clinical outcomes and change in autonomous motivation. We also assess the acceptance and usability of the eMOM app.

Building upon the original randomized controlled trial (RCT), in which the intervention arm used a mobile app (eMOM), we conducted a mixed methods study that included an investigation of eMOM log files, semistructured interviews on self-discovery, and an examination of questionnaires assessing motivation (Treatment Self-Regulation Questionnaire and Perceived Competence Scale), depression (Edinburgh Postnatal Depression Scale), technology use and acceptance (Unified Theory of Acceptance of Use of Technology questionnaire), and usability (modified Software Usability Measurement Inventory). Additionally, we monitored participants' stress levels using wearable electrocardiographic devices (FirstBeat Bodyguard 2). A total of 148 individuals participated in the original RCTs, with 76 in the intervention arm and 72 in the control arm. From the intervention arm, 18 participants were randomly selected for interviews in this study.

Results show that the use rate of eMOM was high, and novel visualization supported self-discovery in persons with GDM. Most participants (17/18, 94%) indicated that the eMOM app helped to find the associations between their daily activities and glucose levels. Especially having nutrition visualized together with glucose was highly appreciated. Participants also reported learning about the associations between physical activity and glucose levels. No differences were observed between the intervention and control arms in autonomous motivation, depression, or stress. Furthermore, there were no correlations between improved clinical outcomes and changes in motivation. Accessibility and usability ratings were consistently high throughout the intervention.

The eMOM mobile app combining data from continuous glucose monitor, food diary, and physical activity tracker supports maternal self-discovery related to GDM without contributing to depression or adding extra stress. This encourages the use of such mobile apps in maternity care. Notably, motivational factors did not correlate with the positive outcomes observed in our prior RCT, suggesting that self-discovery has a greater impact on clinical results.

ClinicalTrials.gov NCT04714762; https://www.clinicaltrials.gov/study/NCT04714762.

To determine the prevalence of depression and anxiety during pregnancy and its association with GDM.

A total of 2141 pregnant women were recruited before 16 weeks of gestation (mean gestational age: 10.5 ± 2.9 weeks) from the STRiDE study in south India. Early GDM (eGDM) was detected in the first trimester, and late GDM (lGDM) during 24-28 weeks, both diagnosed using IADPSG criteria. Depression and anxiety were assessed using the PHQ-9 (score≥10) and GAD-7 (score≥7) scales, respectively.

Overall, 14.9 % had depression and 17.5 % had anxiety in early pregnancy. eGDM was diagnosed in 474 (20.4 %) and lGDM in 321 (19.3 %) women. Women with eGDM had higher prevalence of depression (20.9 %) than those with lGDM (15.6 %, p = 0.06) and those without GDM (13.3 %, p < 0.01). Anxiety was also higher in eGDM (21.1 %) compared to IGDM (15.3 %, p < 0.05) and women without GDM (16.6 %, p < 0.05). eGDM was significantly associated with depression (aOR=1.84, 95 % CI:1.37-2.47, p < 0.001) and anxiety (aOR=1.36, 95 % CI:1.03-1.79, p = 0.03) after adjusting for age, systolic blood pressure, BMI, socioeconomic status, and family history of diabetes.

Women with early GDM have a higher prevalence of depression and anxiety compared to those with late GDM and women without GDM. Early and universal screening for GDM should be done and its association with mental health wellbeing should be explored and supported.

Metformin is well-established as a treatment for type 2 diabetes in non-pregnant individuals. The low cost, acceptability and broad tolerability of metformin have also made it an attractive option for research into the treatment of other conditions associated with insulin resistance. Despite almost 50 years of clinical experience with the use of metformin to treat diabetes in pregnancy, many questions remain regarding its precise effectiveness in different maternal subgroups, as well as potential short-term and long-term effects on the offspring. In this narrative review, we present the current evidence for the use of metformin during pregnancy in various maternal subgroups, including women living with overweight and obesity, women at risk of gestational diabetes, women diagnosed with gestational diabetes and women with pregestational diabetes, including type 2 diabetes. Our specific focus is on the impact of metformin on short-term maternal, fetal and neonatal outcomes. We also consider the evidence for other emerging indications for metformin in pregnancy, such as the prevention and management of pre-eclampsia. PLAIN LANGUAGE SUMMARY: This article looks at research on how metformin use in pregnancy affects mothers and newborns in the short term. Doctors have prescribed metformin since the 1970s for the treatment of diabetes in pregnancy. Despite years of use, there are still questions about how safe and effective metformin is for mothers and their children. Metformin taken during pregnancy moves through the placenta into the foetus's bloodstream. The short-term and long-term effects of metformin on offspring need careful attention. The studies that have looked at the link between metformin use and birth defects have not found any strong link between taking metformin in pregnancy and birth defects, however close attention will continue to be paid in this area. Some large studies have examined the use of metformin in pregnant women who do not have diabetes, but who do live with overweight or obesity. The studies are difficult to compare. Some, but not all, of these studies have shown less weight gain for the mother if metformin is taken by these women during pregnancy. Other large studies have looked at whether metformin can prevent gestational diabetes. The results are mostly disappointing. They suggest that metformin does not stop gestational diabetes from developing. However, the participants in these studies were mostly from white backgrounds and metformin may help prevent gestational diabetes in women of different ethnic backgrounds. However, more research is needed. Metformin has been widely studied as an alternative to insulin for the treatment of gestational diabetes. Because different countries diagnose and treat GDM differently, this makes comparing study results difficult. Women with gestational diabetes seem to gain less weight during pregnancy if they use metformin rather than insulin. Using metformin instead of insulin may result in lower average birth weights for babies from these pregnancies. Also, the use of metformin may lead to fewer babies being born abnormally large. Similarly, large trials have examined the use of metformin in pregnant women who are living with type 2 diabetes. These studies show that metformin can lower a mother's insulin needs. It can also help control weight gain and reduce the risk of having a large baby. One study found that metformin use in women living with Type 2 diabetes might increase the risk of having smaller babies. This was especially true if the mother had high blood pressure or kidney disease. This finding requires further investigation. Metformin might help prevent pre-eclampsia, but this is still unclear. Research is ongoing into a potential role for metformin in the treatment of pre-eclampsia. In conclusion, metformin has been studied in many groups of pregnant women. Women with gestational diabetes or type 2 diabetes may see benefits like less weight gain and better blood sugar/glucose control. Current evidence suggests that metformin shouldn't be used if there are foetal growth issues. It is also not recommended for mothers with high blood pressure or kidney disease. Future studies might find specific groups of pregnant women who would benefit the most from metformin.

Pregnancy guidelines recommend moderate to vigorous physical activity of ≥150 min/week (7000 steps/day) and weight gain specific to prepregnancy weight category. We aimed to assess step and weight changes, with tracking to achieve individualized targets and with coaching conversations on physical activity and eating. The overarching goal was to identify interventions warranting integration and evaluation through a larger trial assessing perinatal outcomes.

In this feasibility trial, we randomized 227 participants (GDM clinics, 5 Canadian cities) to 'track & target,' 'coaching,' 'both,' or 'neither' arms. 'Track & target' participants monitored steps/day (counter) and weight (scale). We delivered weekly targets, applying algorithms that incorporated step and weight data and nudged towards recommendations. Coaching participants conversed weekly with a coach, who applied motivational communication methods. We examined changes in steps/day and weight, between trial entry and 37 weeks' gestation.

Weight change was guideline-concordant across arms. Steps/day averaged 6385 (SD 3406) at baselinue and were stable in the 'track & target' arm (change -59, 95 %CI -749 to 630). The other arms declined (coaching: -915, 95 %CI -1605 to -225; both -1183, 95 %CI -1979 to -386; neither -1456, 95 %CI -2193 to -718).

Our algorithm-driven step target strategy prevents step count decline, meriting study for perinatal impact.

Maternal diabetes might alter fetal brain development. However, well-designed systematic analyses are needed to comprehensively assess and quantify the association between maternal diabetes and neurodevelopmental outcomes in children. We aimed to synthesise and evaluate the available evidence on the effects of maternal diabetes on neurodevelopmental outcomes in children.

For this systematic review and meta-analysis we searched PubMed, Web of Science, Embase, and EBSCO databases from inception to Dec 1, 2024, for studies exploring neurodevelopmental outcomes of children born to mothers with diabetes. The primary outcome was neurodevelopmental disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and International Classification of Diseases 11th Revision. Data were extracted from published reports. Data were pooled with random-effects models and presented as risk ratios or standard mean differences with 95% CIs. This study was prospectively registered on PROSPERO (CRD42023395464).

202 studies, involving 56 082 462 mother-child pairs, were included in the meta-analysis. Of these, 110 (54%) examined gestational diabetes, while 80 (40%) investigated pre-gestational diabetes. Among the total studies reviewed, 169 (84%) exclusively focused on children and adolescents aged up to 18 years. In studies adjusting for at least one key confounder, maternal diabetes was associated with increased risks of all types of neurodevelopmental disorders as well as lower intelligence and psychomotor scores. In studies adjusting for multiple confounders (n=98, 49%), children exposed to maternal diabetes had an increased risk of any neurodevelopmental disorder (risk ratio 1·28; 95% CI 1·24-1·31), autism spectrum disorder (1·25; 1·20-1·31), attention-deficit hyperactivity disorder (1·30; 1·24-1·37), intellectual disability (1·32; 1·18-1·47), specific developmental disorders (1·27; 1·17-1·37), communication disorder (1·20; 1·11-1·28), motor disorder (1·17; 1·10-1·26), and learning disorder (1·16; 1·06-1·26), compared with unexposed children. Maternal pre-gestational diabetes was more strongly associated with the risk of most neurodevelopmental disorders in children than gestational diabetes (risk ratio 1·39; [95% CI 1·34-1·44] vs 1·18 [1·14-1·23]; subgroup difference p<0·0001).

Maternal diabetes is associated with an increased risk of neurodevelopmental disorders and impaired neurodevelopmental performance in children. Further high-quality research is needed to establish causality and clarify the associations between specific types of diabetes and the full spectrum of neurodevelopmental disorders.

The National Natural Science Foundation of China, and the Science and Technology Innovation Program of Hunan Province.

For the Mandarin translation of the abstract see Supplementary Materials section.

Gestational Diabetes Mellitus (GDM) represents a growing challenge worldwide, with significant risks to both women and their babies that extend beyond the duration of the pregnancy and immediate post-partum period. Healthcare professionals (HCPs) play important roles in the screening, diagnosis, treatment and management of women with GDM.

For this qualitative systematic review, a comprehensive search strategy explored the electronic databases Web of Science, CINAHL, Medline, and Scopus, as well as the reference lists of the included papers, for primary studies investigating the experiences, perspectives and practices of HCPs providing care to women with GDM in high-income healthcare settings. Studies were assessed with the Crowe Critical Appraisal Tool, and findings were synthesised using the approach described by Thomas and Harden.

This review included 33 articles - 26 qualitative and seven mixed method studies, representing ten high-income nations. The total number of HCP participants represented across the studies is 989. This figure is constituted by medical professionals (n = 226), nurses and midwives (n = 583), allied health (n = 40) and other or not numerically specified HCPs (n = 140). From 149 findings, four major themes and 10 subthemes were constructed. The four major themes are: multidisciplinary collaboration; healthcare practice; organizational factors; and working with women.

There are barriers to providing optimal care to women with GDM. Including, time and resource constraints, a lack of consensus in practice guidelines, and variable multidisciplinary collaboration. Moving forward, there needs to be a focus on more explicit guidelines, multidisciplinary collaboration, and appropriate resources to support HCPs in providing care to women to manage the short-term and longer-term risks that are associated with a pregnancy affected by GDM.

Isomalto-oligosaccharides (IMO) are prebiotic oligosaccharides that have shown promise in improving insulin sensitivity and glucose metabolism, making them potential therapeutic agents for Type 2 Diabetes (T2D). IMO selectively stimulates beneficial gut microbiota, particularly Bifidobacterium and Lactobacillus, leading to the production of short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate. These SCFAs play a pivotal role in enhancing the release of gut hormones such as GLP-1 (Glucagon-like peptide-1) and PYY (Peptide YY), which improve insulin secretion and promote satiety, thus improving glucose homeostasis. Clinical studies have reported that IMO supplementation can lower HbA1c by 0.5% and reduce postprandial glucose spikes, demonstrating its efficacy in glycemic control. Additionally, IMO promotes insulin sensitivity by reducing inflammation and enhancing adiponectin levels. Although the current findings are promising, further research is needed to determine optimal dosing, long-term safety, and the role of individual gut microbiomes in tailoring IMO interventions. Future studies focusing on personalized nutrition strategies and the synergistic effects of IMO with other lifestyle interventions could enhance its applicability as a key component in T2D management.

Associations of PM2.5 and its constituents with gestational diabetes mellitus (GDM) are still unclear, and little is known about the impact of vitamin B12. The Gene-Environment-Nutrient-Epigenetics interaction on Maternal and Children health study (GENEMaC) cohort was conducted during 2017-2018 in Tianjin, China, and 1396 eligible women were included in the final analysis. Spatiotemporal models were used to estimate PM2.5 exposure levels and its constituents, including sulfate (SO2- 4), ammonium (NH+ 4), nitrate (NO- 3), organic matter (OM), black carbon (BC). Logistic regression and distributed lag non-linear model (DLNM) were used to assess each pollutant-GDM association. Weighted quantile sum (WQS) regression was conducted to assess the extent of contributions of pollutants co-exposure to GDM. The logistic regression showed that exposures to PM2.5, NO- 3, and NH+ 4 during the 2nd trimester of pregnancy increased the risk of GDM. DLNM analyses observed a lag exposure-response relationship for each constituent, while black carbon(BC) exposed in the 2nd trimester was displayed as the top contributor in the WQS model. The joint effects of constituents exposure (high versus low) and serum B12 (tertiles) on GDM were further evaluated, and the highest risks of GDM were consistently observed in the low B12 level and high pollution groups for SO2- 4, NO- 3, and NH+ 4. These findings provide evidence of the impact of PM2.5 components on GDM and highlight the susceptibility of pregnant women with low B12 levels to air pollution.

Given the well-documented endocrine-disrupting effects of phthalate plasticizers (PAEs) on human health, their use has been subjected to stringent regulatory restrictions, prompting a global shift toward non-phthalate plasticizers (non-PAEs) as alternatives. While epidemiological evidence has established significant associations between PAE exposure and gestational diabetes mellitus (GDM), the potential role of non-PAEs in GDM pathogenesis represents a critical knowledge gap in environmental epidemiology. To address this, we conducted a case-control study nested within a well-established prospective birth cohort in Wuhan, China, comprising 286 GDM cases and 286 matched healthy controls. Plasma concentrations of 10 non-PAEs were quantified with high detection frequencies (≥ 70 % for six species). Using multivariable conditional logistic regression and restricted cubic spline regression models adjusted for maternal age, pre-pregnancy body mass index, and other covariates, we identified significant positive associations between gestational exposure to dimethyl azelate (DMAZ), trihexyl trimellitate, di(2-ethylhexyl) maleate, and dibutyl fumarate and elevated GDM risk. In addition, the Bayesian kernel machine regression (BKMR) model further revealed a joint effect of the non-PAE mixture exposure on GDM risk, and DMAZ and diisobutyl adipate/dibutyl adipate (DiBA/DnBA) were identified as key contributors to the joint effect. Our results also demonstrated significant mediation effects of selected lipid molecules (especially phosphatidylcholine and lysophosphatidylcholine) on the associations of DMAZ and DiBA/DnBA with GDM risk. These findings contribute to a deeper understanding of the environmental stressors associated with the development of GDM, as well as the underlying biological mechanisms involving lipid metabolism.

Obesity-induced insulin resistance impairs glucose tolerance and β-cell function, significantly contributing to the pathogenesis of type 2 diabetes (T2D). Protein kinase A (PKA), being one of the key effector molecules of the cyclic AMP (cAMP) pathway, increases insulin secretion via membrane activity, gene expression, and exocytosis of insulin granules. The previous studies were limited to either target cAMP analogs as PKA agonist or mostly flavonoids using In vivo and In vitro studies (Hameed in Int J Biol Macromol 119:149-156, 2018;Shahab in Biomed Pharmacother 177, 2024;Hameed in Eur J Pharmacol 820:245-255, 2018;Hameed in Eur J Pharmacol 858, 2019;Hafizur in Med Chem Res 27:1408-1418, 2018;). To speed up the process, this study aimed to identify potential PKA activators as therapeutic agents for restoring β-cell function in Type 2 Diabetes (T2D) using a multistage virtual screening approach. In the initial phase, a ligand-based pharmacophore model was constructed to screen an in-house small molecule database for potential PKA agonists. By targeting the essential pharmacophoric features necessary for interaction with the cyclic nucleotide-binding (CNB) domain of PKA, the goal was to identify compounds with strong binding affinities and therapeutic promise. To gain deeper insights into the molecular mechanisms of PKA activation and evaluate key interactions and dynamic stability, a subset of promising hits was subjected to all-atom molecular dynamics simulations. Simulations showed significant conformational changes in PKA complexes, with average backbone root mean square deviations (RMSD) of 0.37 ± 0.15 nm for Comp-03, 0.53 ± 0.18 nm for Comp-11, 0.31 ± 0.06 nm for Comp-17, 0.28 ± 0.03 nm for Comp-38, and 0.48 ± 0.13 nm for Comp-41. The N3A motif showed consistent fluctuations, suggesting increased flexibility. Binding free energy calculations showed binding free energies (ΔGbind) for cAMP, Comp-03, Comp-17, Comp-38, and Comp-41, with ΔGbind values of - 62.87 ± 10.04, - 68.57 ± 12.77, - 78.13 ± 16.36, - 62.67 ± 13.06, and - 80.87 ± 10.45 kcal/mol, respectively. To further probe the conformational stability of these complexes, multidimensional scaling and free energy profiling were carried out. This exhaustive research study, involving examination of stability dynamics, deviation patterns, interaction networks, conformational changes, and energy profiles, provides profound understanding about mechanisms that activate PKA. The findings highlight several promising lead compounds, notably Comp-03, Comp-17, Comp-38, and Comp-41, which exhibit superior potential to activate PKA compared to cAMP. These findings lay a strong foundation for the development of novel PKA activators as potential therapeutic agents for managing T2D.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy. Implementation of Value-Based Healthcare (VBHC) to GDM care is worthwhile as traditional GDM care is fragmented and fails to meet the needs of women with GDM. Value of care can be improved through optimization and redesign of the care pathway and implementation of an outcome-based payment model. This study was conducted to perform a value-based evaluation of GDM care pathway redesign by using cost- and outcome data.

This study was designed as a single center, prospective, observational cohort study. In January 2022, GDM care was redesigned by substituting GDM care activities from an Internal Medicine Department (IMD) to an Integrated Maternity Care Organization (IMCO) in the Netherlands. Women diagnosed with GDM in 2021 were assigned to a pre-intervention cohort (N = 264) and those diagnosed in 2022 to a post-intervention cohort (N = 407). The impact of the intervention on value of care for women with GDM was evaluated by comparing clinical outcomes, patient-reported experience measures (GDM Responsiveness questionnaire), and costs (Time-Driven Activity-Based Costing) between the cohorts.

Referrals to the IMD for GDM decreased by 84.8% (pre-intervention: 100%, post-intervention: 15.2%, p <.001), patient-reported experiences significantly improved (Mean responsiveness pre-intervention: 3.46, post-intervention: 3.63, p: 0.00). Initiation of insulin treatment decreased by 46.8% (pre-intervention: 25.0%, post-intervention: 13.3%, p <.001). Maternal- and neonatal clinical outcomes were not different after redesign. Weighted average costs per GDM treatment were 9.7% lower post-intervention (pre-intervention: €168,37, post-intervention: €151,97).

The redesign of GDM care positively impacted value through decreased referrals and improved patient-reported experiences while clinical outcomes remained constant. By de-fragmenting GDM care, cost savings were realized. This study contributes to the improvement of care delivery, particularly in pregnancy and childbirth, by promoting the adoption of comprehensive, value-based evaluations of redesign initiatives and supports the further uptake of VBHC in maternity care.

Previous studies have suggested that pesticide exposure and gut microbiome alterations are associated with gestational diabetes mellitus (GDM) risk. Understanding the complex interactive effect of these factors on GDM is essential. In a cohort of 852 pregnant women, we assessed pesticide levels in serum and analyzed the gut microbiota using 16S rRNA and shotgun metagenomic sequencing. We explored the interactions between pesticides and gut microbiota, assessed their roles in GDM development, and proposed a predictive model based on identified biomarkers. We identified an environmental risk score (ERS), denoting the pesticide mixture level significantly associated with GDM, with the gut microbiota, particularly involving the Dorea branch, playing a crucial mediating role. In addition, we found an interactive effect of pesticide exposure and gut microbiota on GDM risk. Notably, low Prevotella enrichment combined with high ERS arisen from pesticide levels led to a 10.36-fold increased GDM risk. The identified pesticide and gut microbial biomarkers achieved high predictive accuracy for GDM (AUC: 0.833, 95% CI: 0.748-0.918). Collectively, maternal pesticide exposure may induce disrupted microbiome-dependent glycemic alteration, necessitating future assessment of clinical implications. Potential GDM markers can serve as targets for therapeutic intervention caused by pesticides, leading to prevention.

Early gestational diabetes mellitus (eGDM) refers to elevated blood glucose levels not meeting the criteria for overt diabetes before 20 weeks gestation. Observational studies link eGDM to adverse outcomes, but randomized controlled trial (RCT) evidence on early intervention benefits remains inconclusive. To address this, we performed a systematic review and meta-analysis (SRM) of RCTs on this subject.

We searched electronic databases to identify RCTs comparing early treatment vs observation for eGDM. The primary neonatal outcomes analyzed were large-for-gestational age (LGA) and macrosomia. The primary maternal outcome was pregnancy-related hypertension. Secondary neonatal outcomes included neonatal respiratory distress (NRD), neonatal intensive-care unit admission, small-for-gestational age, cord-blood C-peptide ≥90th percentile, and neonatal hypoglycemia. Secondary maternal outcomes were cesarean section (CS), emergency CS, labor induction, preeclampsia, and preterm birth.

Seven RCTs involving 4427 pregnancies were analyzed. The studies differed in their timing and methods of inclusion. Six studies used a combination of lifestyle and pharmaceutical interventions, while 1 relied solely on lifestyle modifications. Early treatment did not reduce LGA [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.53-1.32; P = .44], macrosomia (OR 0.68; 95% CI: 0.43-1.06; P = .09), or pregnancy-related hypertension (OR 1.04; 95% CI: 0.68-1.57; P = .87). Among the secondary outcomes, only NRD was significantly reduced in the treatment arm (OR 0.52; 95% CI: 0.34-0.80; P = .003). However, sensitivity analysis, omitting the lifestyle-only study, demonstrated a lower risk of macrosomia with early intervention (OR 0.55; 95% CI: 0.34-0.91; P = .02).

The SRM demonstrates early intervention does not improve most pregnancy outcomes, except NRD. Sensitivity analysis, excluding the lifestyle-only study, additionally revealed a reduction in macrosomia. The findings must be interpreted cautiously due to the variability in study designs. Replication in well-designed multicenter trials is required before clinical application.

The association between migration and pregnancy outcomes gives contradictory results. Women's socio-economic status explains some differences, but its influence may vary according to women's underlying health conditions. Our aim was to understand how comorbidities modify the relationship between migration and preterm birth or small for gestational age in Belgium.

Data are related to all singleton births to women living in Belgium between 2010 and 2019 (n = 1 200 417). Maternal nationalities were grouped as Belgium, European Union, Eastern Europe, North Africa, Sub-Saharan Africa and the Middle East. A logistic regression was used to estimate the association between maternal nationalities and perinatal outcomes, taking into account the socio-economic status and maternal comorbidities: hypertension, obesity, and diabetes. The interaction effect between maternal nationalities and comorbidities was tested.

Migrant women were more socio-economically disadvantaged than Belgian women. All migrant women without hypertension had a significantly lower Odd Ratio of preterm birth and small for gestational age than Belgian (p < 0.001). In contrast, women with hypertension had a higher OR than Belgian women, even after adjustment for socio-economic status and other comorbidities. This difference was more striking among Sub-Saharan African and Middle Eastern women: respectively, aORs 1.45 (95%CI 1.30-1.62) and 1.24 (95%CI 1.01-1.54) for preterm birth, and aORs 1.17 (95%CI 1.03-1.17) and 1.28 (95%CI 1.02-1.60) for small for gestational age.

Hypertension modifies the association between migration and unfavourable pregnancy outcomes. Although migrant women had a lower risk of preterm birth and small for gestational age than Belgian women, in the presence of hypertension, their risk was significantly higher than Belgian women with the same conditions. Further research is needed to analyse the complex relationships between migration, social status, women's living conditions, and perinatal outcome.

We aim to investigate the association of plant-based diets with the continuous glucose monitoring (CGM)-derived glycemic metrics among gestational diabetes mellitus (GDM) patients. We included 1756 GDM patients in the present analyses and assessed plant-based dietary patterns through constructing a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). CGM-glycemic metrics, such as time in range (TIR), mean blood glucose (MBG), time below range (TBR), low blood glucose index (LBGI), mean of daily differences (MODD), and glycemic risk assessment in diabetes equation (GRADE), were constructed. We found that individuals in the highest quartile of PDI were more likely to have greater TIR (β: 0.28, 95% CI: 0.14 to 0.41) and MBG (β: 0.23, 95% CI: 0.09 to 0.36), while lower TBR (β: -0.26, 95% CI: -0.39 to -0.12), LBGI (β: -0.18, 95% CI: -0.32 to -0.05), and GRADE (β: -0.25, 95% CI: -0.39 to -0.11), compared to those in the lowest quartile. Moreover, most of these associations demonstrated a dose-response relationship, and hPDI and uPDI showed distinct associations with MODD, with higher hPDI favoring a healthier MODD pattern (FDR < 0.05). This study suggests potential benefits of increasing intake of plant-based food for glycemic management among GDM patients.

The precise pathogenic mechanism of long-term detrimental effects on mothers and infants resulting from gestational diabetes (GDM) remains unclear. This study aimed to examine the long-term detrimental consequences of GDM on mothers and newborns, particularly the impact of glucose concentration variations on vascular endothelial cells and its possible pathogenic mechanisms.

An analysis was conducted on the clinical data of 68 healthy pregnant women and 67 pregnant women diagnosed with GDM. Human umbilical vein endothelial cells (HUVECs) were obtained from six pairs of pregnant women for transcriptomic sequencing and analysis, which were concurrently analysed with existing databases. The study examined the effects of varying glucose concentrations on HUVECs, incorporating relevant biological experimental verifications, and assessed oxidative stress, inflammation, and the TGF-β signalling pathway.

Clinical data analysis indicated that in patients with gestational diabetes mellitus, early pregnancy hyperglycemia is significantly linked to adverse pregnancy outcomes, even when blood glucose levels are well-controlled. Transcriptomic sequencing revealed significant alterations in the gene expression of HUVECs under GDM conditions, highlighting enrichment in genes associated with metabolism, inflammation, oxidative stress, and diabetes signalling pathways. Cellular experiments indicated that a transition in glucose concentration from elevated to reduced levels can result in damage and dysfunction in HUVECs, elevate ROS levels, and activate the TGF-β signalling pathway. Additionally, injured HUVECs release CTGF through the TGF-β signalling pathway, influencing the extracellular matrix and surrounding cells.

The findings demonstrate that alterations in glucose concentration, particularly the shift from high to low levels, can lead to vascular endothelial cell dysfunction, increase ROS levels, and are associated with the TGF β/SMAD3 signalling pathway. Furthermore, compromised HUVECs can influence the microenvironment via their secretions, potentially jeopardising the health of both the mother and foetus.

Gestational diabetes mellitus (GDM) is linked to altered fetal development and an increased risk of offspring developing cardiometabolic diseases in adulthood. The mechanisms responsible are unclear; however, GDM is associated with altered fetoplacental vascularisation, fibrosis and endothelial dysfunction. In non-pregnant individuals with diabetes, similar vascular changes are attributed to disruptions in endothelial-to-mesenchymal transition (EndMT), a key process where endothelial cells adopt a mesenchymal phenotype. Here, we assess whether alterations in the fetoplacental macro- and microvasculature are attributed to EndMT, using human umbilical vein endothelial cells (HUVECs) and human term placental tissue, respectively. Transforming growth factor (TGF)-β2 and interleukin (IL)-1β induced morphological and molecular changes consistent with EndMT in both GDM and non-GDM HUVECs. The ability of TGF-β2 and IL-1β to alter expression of known EndMT regulators, VWF, TGFBR1, IL1B and IL1R1, was diminished in GDM HUVECs; however, all other hallmarks of EndMT were similar. In placental villous tissue, Slug and Snail, two key transcriptional regulators of EndMT, were detected in the villous stroma, suggesting that EndMT probably occurs in the placental microvasculature. We observed a reduction in endothelial marker genes PECAM1, VWF and CDH5 in GDM placentas, suggesting reduced placental vascularisation. This was accompanied by a reduction in EndMT regulators SNAI2, TGB2, TGFB3 and TGFBR2; however, there was no change in mesenchymal markers or other EndMT regulators. This suggests that there may be some alterations in EndMT in GDM but this probably does not fully explain the endothelial dysfunction and altered vascularisation that occurs in the fetoplacental vasculature in pregnancies complicated by GDM. KEY POINTS: Gestational diabetes mellitus (GDM) has been linked to altered placental vascularisation, fibrosis and endothelial dysfunction. Disruptions in endothelial-to-mesenchymal transition (EndMT), a process where endothelial cells adopt a mesenchymal phenotype, has been linked to vascular complications in diabetes, but EndMT in GDM has not been investigated. Transforming growth factor (TGF)-β2 and interleukin (IL)-1β induced morphological and molecular changes consistent with EndMT in GDM and non-GDM human umbilical vein endothelial cells (HUVECs). Although the expression of EndMT mediators, VWF, TGFBR1, IL1B, and IL1R1, was diminished in GDM HUVECs, other EndMT hallmarks were similar. Transcriptional regulators of EndMT, Slug and Snail, were detected in the human term placenta. Despite a reduction in endothelial markers, PECAM1, VWF and CDH5, as well as SNAI2, TGFB2/3 and TGFBR2 in GDM placenta, there was no change in mesenchymal or other EndMT markers. This suggests that, although there may be some changes to EndMT in GDM, the vascular dysfunction is probably not explained fully by alterations in EndMT.

Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, adversely affects maternal and fetal health. This study investigated the impact of vitamin D3 (VD3) deficiency or supplementation on placental long chain polyunsaturated fatty acid (LCPUFA) metabolism, one-carbon cycle metabolites, inflammation, oxidative stress, angiogenesis, and birth outcomes in a GDM rat model. Wistar rats were divided into five groups: Control (1000 IU VD3/kg diet), Vitamin D Deficient (VDD, 0 IU VD3/kg diet), GDM (1000 IU VD3/kg diet + GDM), VD3 supplementation with 1500 IU (VDS-1500 +GDM), and VD3 supplementation with 10,000 IU (VDS-10,000 +GDM). GDM was induced using a high-fat, high-sugar diet and streptozotocin. Diets were provided from weaning through pregnancy. Only the VDS-10,000 +GDM group achieved sufficient serum 25(OH)D levels (>30 ng/ml). 10,000 IU/kg VD3 supplementation reduced gestational weight gain and improved fetal/placental weight ratios. It reduced the levels of FBS, fasting insulin, and HOMA-IR, while increased HOMA-IS. It regulated calcium homeostasis by decreasing parathyroid hormone and increasing phosphorous levels. It normalized one-carbon metabolites, reducing homocysteine and increasing folate levels. Both doses of VD3 supplementation mitigated oxidative stress, reducing malondialdehyde levels, which was higher in GDM and VDD groups. It restored LCPUFA profiles, increasing arachidonic acid and decreasing n-6 linoleic acid levels. High-dose VD3 reduced elevated plasma and placental TNF-α levels and downregulated IL-6 mRNA in the GDM group, while IL-6 protein levels remained comparable. The protein and mRNA levels of both VEGF and VEGF-R1 were higher in GDM group. 10,000 IU VD3 reduces VEGF levels whereas, 1500 IU VD3 reduces VEGF-R1 levels. High-dose VD3 supplementation (10,000 IU/kg) during pregnancy effectively improved vitamin D status and positively influenced placental metabolic pathways, oxidative stress, inflammation, and angiogenesis, thereby improving pregnancy outcomes in GDM.

Gestational diabetes mellitus (GDM), characterized by insulin resistance (IR) and β-cell dysfunction, is one of the most common complications of pregnancy with unmet needs of prevention methods.

To investigate the causal role of insulin resistance and metabolic pathways in the pathogenesis of GDM with our proposed high-dimensional systematic Mendelian randomization (hdsMR) framework.

Cases with GDM and controls with normal glucose tolerance were recruited at the University of Hong Kong-Shenzhen Hospital from 2015 to 2018. A total of 566 participants (aged > 18 years), including 274 with GDM, were enrolled after excluding subjects with major chronic diseases or long-term use of medications affecting glycolipid metabolism. Clinical characteristics and serum samples were collected during the GDM screening stage, and the genome and metabolome were tested. A novel hdsMR framework was proposed to estimate the causal role of IR index (Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) and metabolic pathways in the pathogenesis of GDM.

Our hdsMR method confirmed that HOMA-IR was causal to GDM (odds ratio, 1.17; 95% confidence interval, 1.04-1.32) and revealed that two metabolic pathways (glyoxylate and dicarboxylate metabolism pathway and lysine degradation pathway) mediated 14.6% and 8.4%, respectively, between HOMA-IR and GDM. In an independent validation cohort comprising 255 pre-diabetic individuals, we showed that both pathways could be intervened through diet (P < 0.05). Furthermore, glyoxylate and dicarboxylate metabolism pathway was significantly associated with adverse pregnancy outcomes in GDM.

These results indicated that targeting specific metabolic pathways through dietary intervention is worth exploring as a possible GDM prevention approach, and hdsMR is more efficient in finding causal mediating metabolic pathways than traditional MR methods.

Gestational diabetes mellitus (GDM) is a prevalent pregnancy disorder. In recent years, numerous studies have affirmed the augmented risk of obesity and diabetes mellitus in the offspring of affected individuals. Exclusive breastfeeding has been vigorously advocated as an infant feeding practice in various countries. We aimed to test our hypothesis that human milk of women with gestational diabetes differs from that of non-GDM women.

For this systematic review and meta-analysis, we searched the CNKI, PubMed, Web of Science databases, and citations for studies published between Jan 1,2000 and Sep 26, 2024. We included all studies related to human milk macronutrients. We did separate meta-analyses for carbohydrates, proteins, lipids, and energy of the colostrum and mature human milk. All analyses were performed using Revman 5.4.1 (Review Manager). The quality of the evidence was assessed with the NOS scale. Registration does not apply.

Of 377 records identified, 9 records were available, all of which had a moderate to high quality. Compared to non-GDM women, the colostrum of GDM women exhibited a higher protein content (MD = 0.04, 95% CI: 0.00~0.07, P = 0.03), while there were no significant disparities in carbohydrates, lipids, and energy. Simultaneously, the mature human milk of GDM women had a higher protein content (MD = 0.01, 95% CI: 0.00~0.02, P = 0.007) and a higher lipid content (MD = 0.19, 95% CI: 0.08~0.31, P = 0.001), with no significant differences in carbohydrates and energy.

There are many factors affecting the composition of human milk and fewer studies have been conducted on the composition of human milk. More high-quality studies are needed to validate the relationship between macronutrients in colostrum and carbohydrate in mature milk content with GDM.

Pregnant women face a higher risk of developing gestational diabetes mellitus (GDM) due to the poor dietary habits. GDM can influence the health of both mothers and child. As food processing develops, pregnant women inevitably consume artificial sweeteners, among with the three most common are sucralose, aspartame, and sodium saccharin. It is a concern whether artificial sweeteners consumed during pregnancy increases GDM risk.

To analyze the association between artificial sweetener consumption during pregnancy and the incidence of GDM.

422 pregnant women from a Guangdong hospital were surveyed through convenience sampling. The questionnaire collected general information, artificial sweeteners consumption and other GDM related factors. According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG), GDM was diagnosed was met the 75g oral glucose tolerance test (OGTT) at any time of pregnancy. The consumption of artificial sweeteners was categorized into low and high-consumption groups according to a four-point scale. A multifactorial logistic regression model was used to control for confounders and analyze the association between artificial sweetener consumption andGDM.

This study included 422 pregnant women with a mean age of (32 ± 3.73) years and a GDM incidence of 13.74%. The GDM incidence was higher in the high artificial sweeteners consumption group (56.90%), than in the low consumption group (43.10%) (p < 0.05). Increased artificial sweetener consumption was linked to a higher GDM risk (OR=2.66,95% CI: 1.48-1.78). High artificial sweeteners consumption was a GDM risk factor in BMI-stratified analyses.

High consumption of artificial sweeteners, like sucralose, aspartame, and sodium saccharin, is linked to increased risk of GDM in pregnant women. Further research is required to confirm results and explore mechanism, guiding healthy eating habits during pregnancy.

To investigate the association of pancreatic duodenal homeobox-1 (PDX1) in early pregnancy with the risks of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes.

A total of 231 pregnant women were recruited at their initial antenatal care visit during 8-12 gestational weeks in this study. The 75g OGTT was performed during 24-28 gestational weeks. Blood samples were collected to measure PDX1 levels. Participants were followed throughout their pregnancy to monitor for the development of GDM and adverse pregnancy outcomes. The odds ratio (OR) was used to assess the risks of GDM and adverse pregnancy outcomes.

Pregnant women in the GDM group had higher levels of HOMA-IR and TyG index, and lower PDX1 levels both in early and mid-pregnancy (P<0.05), but had lower HOMA-β levels only in mid-pregnancy (P<0.05). PDX1 in early pregnancy was negatively correlated with FPG, 2h PG, HOMA-IR, and TyG, while positively correlated with HOMA-β in mid-pregnancy (P<0.05). The adjusted analysis showed that elevated PDX1 levels in early pregnancy were associated with reduced risks of GDM (aOR 0.287, 95%CI 0.130-0.636, P=0.002), macrosomia (aOR 0.249, 95%CI 0.076-0.811, P=0.021) and composite adverse pregnancy outcomes (aOR 0.496, 95%CI 0.256-0.960, P=0.037).

Elevated PDX1 in early pregnancy was associated with decreased risks of GDM and adverse pregnancy outcomes.

Hormonal fluctuations across the female reproductive lifespan lead to physiological adjustments that impact insulin sensitivity and glucose metabolism, generating unique challenges in diabetes management. Although current guidelines focus primarily on diabetes care during pregnancy, they lack tailored recommendations for addressing glycaemic variability associated with menstrual cycles, contraceptive needs, and menopause. Low rates of prepregnancy counselling, limited contraceptive guidance, and underuse of hormone replacement therapy further complicate care for women with diabetes. Here we examine these care gaps, identify unmet needs across reproductive stages, and suggest research directions to develop comprehensive, stage-specific management strategies that better support women's health and improve diabetes outcomes throughout the reproductive years.

Maternal high level of folate and low level of vitamin B12, namely "folate and vitamin B12 imbalance", has been found to be associated with metabolic disorders, such as gestational diabetes mellitus (GDM). The aims of this study were to explore the associations of maternal serum folate, vitamin B12 and their imbalance in early pregnancy with GDM, and to explore the potential mediation effects of the methionine cycle related metabolites on the above associations.

This nested case-control study (172 GDM case-control pairs) was conducted based on a prospective birth cohort. Serum concentrations of 5-methyltetrahydrofolate (5-MTHF), vitamin B12 and methionine cycle related metabolites [S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and Homocysteine (Hcy)] were detected. 5-MTHF (nmol/L)/vitamin B12 (pmol/L) times 1000 was calculated to indicate the imbalance status of folate and vitamin B12. Conditional logistic regression was performed to analyze the associations of 5-MTHF, vitamin B12 and their imbalance with GDM. The mediation effect models were applied to explore the mechanism.

High serum level of 5-MTHF in early pregnancy was related to a higher risk of GDM (OR = 2.00, 95%CI: 1.19-3.37). Compared with the group of the lowest tertile concentration of vitamin B12, the group of the highest concentration had a lower risk of GDM (OR = 0.33, 95%CI: 0.11-0.97). Higher 5-MTHF/vitamin B12 was associated with a higher risk of GDM (OR = 1.67, 95%CI: 1.08-2.56). Besides, no significant mediation effect of methionine cycle related metabolites was found on the associations of folate, vitamin B12 and the imbalance status with the risk of GDM.

High maternal serum folate, low vitamin B12 levels and the resulting imbalance may increase the risk of GDM. The theory of "folate trap" could not explain the effect of folate, vitamin B12 and their imbalance on GDM.

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with adverse short-term and long-term health outcomes for both mother and child. This study aimed to investigate the association between plasma amino acid concentrations and the incidence of GDM from 2019 to 2021.

Plasma levels of 37 amino acids were precisely measured using triple quadrupole mass spectrometry. The principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models identified metabolic differences between GDM and non-GDM groups. Conditional logistic regression, generalized linear model, and quantile g-computation were employed to assess the associations between individual or combined amino acids and GDM risk/blood glucose levels. The discriminatory power of various factors associated with the risk of GDM was evaluated using the area under the receiver operating characteristic curve (AUC-ROC).

A total of 969 pregnant women were included in this case-control study. OPLS-DA model identified 16 biomarkers that differentiated the GDM and non-GDM groups. After adjusting for potential covariates and correcting for multiple testing, conditional logistic regression analysis revealed that certain key amino acids, such as valine and isoleucine, were positively associated with the incidence of GDM, while glycine and serine were negatively associated with GDM risk (OR = 0.753-1.671, Pfdr = <0.001-0.001). Generalized linear model analysis showed that specific amino acids, including alpha-aminoadipic acid and arginine, were positively associated with blood glucose levels, while glycine and serine were negatively associated (β = -0.211-0.365, Pfdr = <0.001-0.045). Additionally, mixtures of the identified amino acids were significantly associated with an increased risk of GDM (P < 0.001). The combination of selected amino acids showed the highest ability to identify GDM in comparison with traditional risk factors and specific amino acids (AUC-ROC = 0.761, 95 % CI: 0.729-0.792). The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified two metabolic pathways related to GDM risk: "Glycine, Serine, and Threonine Metabolism" and "Arginine biosynthesis".

The overall amino acid profile, rather than disturbances in specific amino acids, may serve as a more important prevention or therapeutic target for GDM.

The microvascular system is essential for delivering oxygen and nutrients to tissues while removing metabolic waste. During pregnancy, the uteroplacental microvascular system undergoes extensive remodeling to meet the increased demands of the fetus. Key adaptations include vessel dilation and increases in vascular volume, density, and permeability, all of which ensure adequate placental perfusion while maintaining stable maternal blood pressure. Structural and functional abnormalities in the uteroplacental microvasculature are associated with various gestational complications, posing both immediate and long-term risks to the health of both mother and infant. In this review, we describe the changes in uteroplacental microvessels during pregnancy, discuss the pathogenic mechanisms underlying diseases such as preeclampsia, fetal growth restriction, and gestational diabetes, and summarize current clinical and research approaches for monitoring microvascular health. We also provide an update on research models for gestational microvascular complications and explore solutions to several unresolved challenges. With advancements in research techniques, we anticipate significant progress in understanding and managing these diseases, ultimately leading to new therapeutic strategies to improve maternal and fetal health.

We explored the effect of beta-thalassemia major on pregnancy and delivery outcomes in non-endemic area, utilizing USA population database.

This is a retrospective study utilizing data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. A cohort of all deliveries between 2011 and 2014 was created using ICD-9 codes. The patients with beta-thalassemia major were identified and matched to patients without beta-thalassemia based on age, race, income quartile, and type of health insurance at a ratio of 1:20. The baseline characteristics were compared between the groups using Chi-square and Fischer's exact tests, as appropriate. The univariate and multivariate analyses were conducted for pregnancy, delivery and neonatal outcomes to estimate the unadjusted and adjusted odds ratio, respectively.

Out of 3,070,656 pregnancies over the study period, beta-thalassemia major complicated 445 pregnancies. The patients with beta-thalassemia were more likely to have thyroid disorders and previous C-section (p-value < 0.05). There were no differences in pregnancy outcomes such as gestational hypertension, preeclampsia, gestational diabetes, and placenta previa. C-section was 30% more likely to be the method of birth (aOR 1.30, 95%CI 1.03-1.63) and there was more than three-fold increase in rate of blood transfusion (aOR 4.69, 95% CI 3.02-7.28) among participants with beta-thalassemia major. Mothers with beta-thalassemia, almost, were 70% more likely to have a neonate small for gestational age (aOR 1.68, 95%CI 1.07-2.62).

Women with beta-thalassemia major are more likely to give birth by C-section, require blood transfusion and have small for gestational age neonates. Counseling patients with beta-thalassemia about these risks and increased antenatal surveillance is advised.

The relationship between iodine status and gestational diabetes mellitus (GDM) is inconclusive. This study aimed to explore the trajectories of urinary iodine concentrations (UIC) in pregnant women before GDM diagnosis and to assess the associations between maternal UIC trajectories and the risk of developing GDM.

A prospective cohort study was conducted in China. Data from 1076 pregnant women who were recruited between August 2019 and December 2021 were analyzed. GDM screening was performed at the 28th week of pregnancy. Arsenic and cerium catalysis spectrophotometry was used to measure UIC. The latent class model was used to identify distinct UIC trajectories in pregnant women, using multiple urine specimens. We evaluated the association of UIC trajectories with the risk of GDM by logistic regression analysis.

Three maternal UIC trajectories were identified: (1) high-stable trajectory (72.12%), (2) high-decreasing trajectory (3.07%), and (3) low-stable trajectory (24.81%). Compared with the pregnant women in high-stable trajectory group, women in the low-stable UIC trajectory group showed an increased risk of GDM before adjustment of covariates (OR: 1.58, 95% CI: 1.08-2.27). After adjusting for different covariates, a statistically significant association was observed only between low-stable trajectory trajectories and GDM.

This study highlights a relationship between UIC and the risk of GDM. To better prevent iodine deficiency and GDM, persistent sufficient iodine status from pregnancy to delivery, should be emphasized.

Two-dimensional speckle-tracking echocardiography (2D-STE) has emerged as a valuable tool for assessing cardiac function in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM).

This review synthesizes recent studies utilizing 2D-STE in diabetic patients, highlighting its clinical applications and findings.

In this review, relevant studies were identified through comprehensive searches of major scientific databases, including PubMed, Scopus, Google Scholar, ScienceDirect, and other reputable sources.

The results of this study indicate that 2D-STE is capable of detecting subclinical cardiac dysfunction in patients with both T1DM and T2DM, even in instances where conventional echocardiographic parameters appear to be within normal limits. Assessment of right ventricular (RV) function through 2D-STE has demonstrated impaired right ventricular free wall longitudinal strain (RVFWLS) and global longitudinal strain (RVGLS) in individuals with T2DM, which correlates with suboptimal glycemic control. Furthermore, evaluation of left ventricular (LV) function has revealed decreased global longitudinal strain (GLS) and impaired LV twist mechanics in T2DM patients, particularly under conditions of physiological stress. In T1DM patients, 2D-STE has identified early changes in myocardial deformation, with studies reporting reduced LV and RV strain values compared to healthy controls. The technique has also been effective in assessing the impact of disease duration and glycemic control on cardiac function in both T1DM and T2DM.

These findings underscore the potential of 2D-STE as a sensitive and comprehensive tool for early detection of cardiac dysfunction in both T1DM and T2DM, potentially guiding management strategies and improving outcomes in these high-risk populations.

To assess the completion of the type 2 diabetes, heart disease and stroke prevention program (the Life!) among women with a history of gestational diabetes mellitus (GDM) according to participants' characteristics.

Data from women with a history of GDM enrolled in the Life! program in Victoria, Australia, between 2014 and 2022 were analysed. Completion rates were assessed using the PROGRESS-Plus (Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social capital Plus age and smoking) framework. Multivariable logistic regression model was fitted.

A total of 2399 women with a history of GDM were enrolled in the program, of which 55 % completed it. Characteristics associated with higher completion rates included being from metropolitan areas (AOR = 1.52, 95 % CI: 1.14-2.01) compared with being from regional areas, having a body mass index in a normal range (AOR = 1.50, 95 % CI: 1.06-2.15) compared with having overweight or obesity, having middle income (AOR = 1.41, 95 % CI: 1.01-1.98) compared with having low- or high-income, and enrolment after 2019 (AOR = 2.3, 95 % CI:1.80-3.06) compared with enrolment in 2019 or earlier. Conversely, having a South or Central Asian background (AOR = 0.65, 95 % CI: 0.46-0.92) is associated with a lower completion rate compared with being from Australia.

Characteristics associated with lower completion rates among women with prior GDM in a cardiometabolic risk reduction program included residing in rural and remote areas, having an elevated BMI (in the overweight or obesity range), low or high income, enrolment in 2019 or earlier and being of South or Central Asian background.