BACKGROUND: Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP\'s predictive capability for GDM.
METHODS: This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM.
RESULTS: The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27-1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087-0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557.
CONCLUSIONS: This study revealed that the AIP at 10-14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies.
BACKGROUND: ClinicalTrials.gov registration no. NCT02276144.

OBJECTIVE: We aimed to explore the relationship between dietary patterns and gestational diabetes mellitus (GDM) during pre-pregnancy six months using principal component analysis (PCA) and the geometric framework for nutrition (GFN).
METHODS: We conducted a case-control study that included 210 GDM pregnant women and 210 controls. The dietary intake of all participants was assessed by a validated semi-quantitative food frequency questionnaire (FFQ). Major dietary patterns were extracted by PCA. A conditional logistic regression model was used to determine whether specific dietary patterns are associated with the risk of GDM. Meanwhile, the relationship between dietary patterns and GDM was visualized using GFN.
RESULTS: Four major dietary patterns were identified: \"protein-rich pattern,\" \"plant-based pattern,\" \"oil-pickles-desserts pattern,\" and \"cereals-nuts pattern.\" After adjustment for confounders, the \"plant-based pattern\" was associated with decreased risk of GDM (Q4 vs. Q1: OR = 0.01, 95% CI: 0.00-0.08), whereas no significant association was found in other dietary patterns. Moreover, there was no dietary intake of ice cream cones and deep-fried dough sticks for the population, which would produce fewer patients with GDM. Deep-fried dough sticks had statistically significant differences in the case and control groups (p < 0.001), while ice cream cones had the opposite result.
CONCLUSIONS: The \"plant-based pattern\" may reduce the risk of GDM. Besides, although the \"cereals-nuts pattern\" had no association with GDM risk, avoiding the intake of deep-fried dough sticks could decrease GDM risk.

OBJECTIVE: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship.
METHODS: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity.
RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05).
CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.

UNASSIGNED: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication during pregnancy. We aimed to evaluate a risk prediction model of GDM based on traditional and genetic factors.
UNASSIGNED: A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to gather general data. Serum test results were collected from the laboratory information system. Independent risk factors for GDM were identified using univariate and multivariate logistic regression analyses. A GDM risk prediction model was constructed and evaluated with the Hosmer-Lemeshow goodness-of-fit test, goodness-of-fit calibration plot, receiver operating characteristic curve and area under the curve.
UNASSIGNED: Among traditional factors, age ≥30 years, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms (SNPs) (rs2779116, rs5215, rs11605924, rs7072268, rs7172432, rs10811661, rs2191349, rs10830963, rs174550, rs13266634 and rs11071657) were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk.
UNASSIGNED: Both genetic and traditional factors contribute to the risk of GDM in women, operating through diverse mechanisms. Strengthening the risk prediction of SNPs for postpartum DM among women with GDM history is crucial for maternal and child health protection.
We aimed to evaluate a risk prediction model of gestational diabetes mellitus (GDM) based on traditional and genetic factors. A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to collect general data. Among traditional factors, age ≥30 years old, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. Both genetic and traditional factors increase the risk of GDM in women.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4-6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore.
METHODS: The study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child\'s socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the \"LVL UP App\", a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily \"Life Hacks\" (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the \"HAPPY App\", a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period.
CONCLUSIONS: High rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs.
METHODS: The protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023.
BACKGROUND: ClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023.

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21\'s impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21\'s efficacy.

Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the development of diabetes. However, the underlying mechanisms that regulate the polarization of ATMs associated with gestational diabetes mellitus (GDM) remain unclear. Thus, we aimed to determine the effects of abnormal fatty acids on macrophage polarization and development of insulin resistance in GDM. Levels of fatty acids and inflammation were assessed in the serum samples and adipose tissues of patients with GDM. An in vitro cell model treated with palmitic acid was established, and the mechanisms of palmitic acid in regulating macrophage polarization was clarified. The effects of excessive palmitic acid on the regulation of histone methylations and IR were also explored in the high-fat diet induced GDM mice model. We found that pregnancies with GDM were associated with increased levels of serum fatty acids, and inflammation and IR in adipose tissues. Increased palmitic acid could induce mitochondrial dysfunction and excessive ROS levels in macrophages, leading to abnormal cytoplasmic and nuclear metabolism of succinate and α-ketoglutarate (αKG). Specifically, a decreased nuclear αKG/succinate ratio could attenuate the enrichment of H3K27me3 at the promoters of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, leading to cytokine secretion. Importantly, GDM mice treated with GSK-J4, an inhibitor of histone lysine demethylase, were protected from abnormal pro-inflammatory macrophage polarization and excessive production of pro-inflammatory cytokines. Our findings highlight the importance of the metabolism of αKG and succinate as transcriptional modulators in regulating the polarization of ATMs and the insulin sensitivity of adipose tissue, ensuring a normal pregnancy. This novel insight sheds new light on gestational fatty acid metabolism and epigenetic alterations associated with GDM.

OBJECTIVE: To determine risk factors for 1-year postpartum weight retention (PPWR) and glucose intolerance (prediabetes + diabetes) in women with a previous history of gestational diabetes (GDM) and prediabetes in early postpartum.
METHODS: In this exploratory analysis of the MELINDA randomized controlled trial, we report data of 167 women with prediabetes at the 6-16 weeks (early) postpartum oral glucose tolerance test after a recent history of GDM.
RESULTS: Of all participants, 45% (75) had PPWR >0 kg at 1-year postpartum. Compared to women without PPWR, women with PPWR had higher gestational weight gain [10.5 ± 6.4 vs. 6.5 ± 4.5 kg, p < 0.001], higher BMI (p < 0.01) and a worse metabolic profile (higher waist circumference, worse lipid profile and more insulin resistance) (all p < 0.05) both in early and late postpartum. Of all women with PPWR, 40.0% developed metabolic syndrome, compared to 18.9% of women without late PPWR (p = 0.003). The only independent predictor for late PPWR was weight retention in early postpartum (p < 0.001). Of all participants, 55.1% (92) had glucose intolerance (84 prediabetes, 8 diabetes) 1-year postpartum. Independent predictors for late postpartum glucose intolerance were lower gestational age at start insulin therapy in pregnancy and delivery by caesarean section (resp. p = 0.044 and 0.014).
CONCLUSIONS: In women with a previous history of GDM and prediabetes in early postpartum, PPWR in early postpartum was a strong independent predictor for late PPWR, while earlier start of insulin therapy during pregnancy and delivery by caesarean section were independent predictors of glucose intolerance in late postpartum.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant\'s gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

OBJECTIVE: To investigate the positive rate of late-onset gestational diabetes mellitus (GDM) by additional fasting blood glucose (FBG) screening at 32-34 gestational weeks (GW) and analyse the perinatal outcomes of late-onset GDM after standard treatment.
METHODS: An Prospective cohort study.
METHODS: Single centre in China.
METHODS: 1130 singleton pregnancies with negative GDM screening in their first and second trimester.
METHODS: Additional FBG testing was performed at 32-34 GW. Pregnancies with FBG ≥5.1 mmol/L were diagnosed as GDM and received standardized treatment. Perinatal outcomes were collected and compared.
METHODS: Diagnosis of late-onset GDM, obstetric and neonatal outcomes.
RESULTS: 6.3% (71/1130) of participants had FBG values ≥5.1 mmol/L and were diagnosed with late-onset GDM. Sixty-five (91.5%) were treated by dietary therapy and 6 (8.5%) by insulin therapy. The perinatal outcomes of full-term delivery were compared. The incidence of macrosomia (22.7% vs. 5.1%, adjusted odds ratio (aOR) 5.51, 95% confidence interval (CI) 1.83-16.61, p = 0.002) and NICU transferring (18.3% vs. 10.1%, aOR 1.94, 95% CI 1.01-3.74, p = 0.046) was significantly higher in late-onset GDM group than that in FBG <5.1 mmol/L group. Elevated FBG was associated with overweight or obesity during pregnancy (54.9% vs. 34.9%, OR 2.27, 95% CI 1.40-3.68, p = 0.001).
CONCLUSIONS: 6.3% of singleton pregnancies with normal GDM screening results in the first and second trimester were found to have late-onset GDM by additional FBG screening at 32-34 GW, and their risk of macrosomia during a full-term pregnancy remains significantly higher after standard treatment.