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ObjectivesThis study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk.DesignWe conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk.ResultsOf the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction.ConclusionsLPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations.

A study published in the journal Diabetes, Obesity & Metabolism found that children born to mothers with gestational diabetes have an increased risk of being overweight as they grow up. The study also found that intensive treatment of gestational diabetes during pregnancy improved outcomes for both mother and baby, but did not reduce the risk of childhood obesity. The researchers suggest that prevention and intensive management of gestational diabetes are important in reducing the risk of childhood obesity. They also recommend that children from gestational diabetes pregnancies adopt a healthy lifestyle from an early age to reduce the risk of future health problems. Further research is needed to better understand these relationships and develop effective health management strategies for women with gestational diabetes and their children. [Extracted from the article]

To examine long-term risk of overweight in offspring of women with gestational diabetes mellitus (GDM) defined by the International Association of Diabetes and Pregnancy Study Group (IADPSG)'s criteria but not by the 1999 World Health Organization (WHO)'s criteria. We followed up 1681 mother-child pairs for 8 years in Tianjin, China. Overweight in children aged 1–5 and 6–8 were respectively defined as body mass index-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of hyperglycemia indices at oral glucose tolerance test and GDMs defined by different criteria for offspring overweight at different ages. Offspring of women with fasting plasma glucose ≥5.1 mmol/L were at increased risk of overweight at 6–8 years old (OR:1.45, 95% CI: 1.09–1.93). GDM defined by the IADPSG's criteria only was associated with increased risk of childhood overweight at 6–8 years old (1.65, 1.13–2.40), as compared with non-GDM by either of the two sets of criteria. Newly defined GDM by the IADPSG's criteria increased the risk of offspring overweight aged 6–8 years. • Maternal fasting PG ≥5.1 mmol/L increased risk of childhood overweight aged 6–8. • GDM defined by IADPSG's criteria increased risk of childhood overweight aged 6–8. • Supporting use of IADPSG's criteria in the population of Chinese pregnant women. • Emphasizing children of GDM adopts active lifestyle for health benefits in future. [ABSTRACT FROM AUTHOR]

Aims: To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre‐pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. Materials and Methods: One thousand six hundred and eighty one mother‐child pairs were followed for 8 years in Tianjin, China. Group‐based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre‐pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut‐off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre‐pregnancy BMI for adverse growth patterns. Results: Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre‐pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74–3.25 & 4.92, 2.26–10.73). GDM greatly enhanced the adjusted OR of high pre‐pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25–5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. Conclusions: Maternal high pre‐pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre‐pregnancy BMI for LOGP. [ABSTRACT FROM AUTHOR]

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

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

Summary: Objective: To explore associations of maternal insulin resistance and β‐cell dysfunction with offspring overweight before 24 months of age among children of Chinese women with gestational diabetes mellitus (GDM). Methods: Offspring of women with GDM (n = 901) who were enrolled in a lifestyle trial during pregnancy were followed up to 24 months of age in Tianjin, China. Restricted cubic spline analysis was performed to examine full‐range associations of maternal homeostatic model assessment of insulin resistance (HOMA‐IR) and β‐cell function (HOMA‐%β) with childhood overweight. Logistic regression was performed to obtain the odds ratios (ORs) and 95% confidence interval (CI) of maternal high HOMA‐IR and low HOMA‐%β at diagnosis of GDM for offspring overweight within 12 months of age and at 13–24 months of age. Results: Maternal high HOMA‐IR was associated with an increased risk of offspring being overweight within 12 months of age and at 13–24 months of age (OR: 1.71, 95%CI: 1.12–2.62 & 1.89, 1.13–3.17, respectively). Maternal low HOMA‐%β was associated with an increased risk of offspring being overweight at 13–24 months of age (1.64, 1.05–2.55). Conclusions: Both maternal increased insulin resistance and decreased β‐cell function at diagnosis of GDM were associated with elevated risk of offspring overweight in early childhood among Chinese women with GDM. [ABSTRACT FROM AUTHOR]

To examine the associations of parental obesity prior to pregnancy with offspring overweight before two years of age among children of Chinese women with gestational diabetes mellitus (GDM). Offspring of women with GDM (n = 774) who were diagnosed in 2010–2012 were followed up to two years of age in Tianjin, China. Multinomial logistic regression was used to obtain odds ratios (ORs) and 95% confidence interval (CI) of maternal and paternal prepregnancy obesity with offspring overweight at < 1, 1–1.5, and 1.5–2 years of age. Among 774 offspring of women with GDM, 457 (59.0%) of the offspring developed overweight before two years of age. Maternal prepregnancy obesity was associated with increased risk of offspring overweight at 1–1.5 years of age and 1.5–2 years of age (ORs: 1.98, 95%CI: 1.09–3.59 & 2.14, 1.10–4.15, respectively). Paternal prepregnancy obesity was only associated with elevated risk of offspring overweight at 1.5–2 years of age (1.82, 1.08–3.06). Furthermore, copresence of both maternal and paternal obesity prior to pregnancy had an additive effect on the risk of offspring overweight at 1.5–2 years of age (3.73, 1.50–9.27). Parental prepregnancy obesity predicted offspring overweight before two years of age among children of Chinese women with GDM. • Among Chinese women with gestational diabetes mellitus, we found: • Maternal prepregnancy obesity predicted offspring overweight before 2 years of age. • Paternal prepregnancy obesity predicted offspring overweight before 2 years of age. • Maternal and paternal obesity had an additive effect on the offspring overweight. • Risk of overweight increased with age in the offspring of parents with obesity. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether a 9-month intensive lifestyle intervention could lead to weight loss and improve cardiovascular risk factors among young women with both gestational diabetes mellitus (GDM) and newly diagnosed diabetes. A total of 83 young women, who had GDM and were subsequently diagnosed as type 2 diabetes at an average of 2.6 years after delivery, participated in a 9-month intensive lifestyle intervention and a follow-up survey at 6–9 years postintervention. After the 9-month intervention, these women had a weight loss of 2.90 kg (−4.02% of initial weight), decreased waist circumference (−3.12 cm), body fat (−1.75%), diastolic blood pressure (−3.49 mmHg), fasting glucose (−0.98 mmol/L) and HbA1c (−0.72%). During the 6–9 years postintervention period, they still had lower weight (−3.71 kg; −4.62% of initial weight), decreased waist circumference (−4.56 cm) and body fat (−2.10%), but showed a slight increase in HbA1c (0.22%). The prevalence of using glucose-lowering agents increased from 2.4% at baseline to 34.6% after the 9-month lifestyle intervention, and to 48.4% at 6–9 years postintervention. A 9-month intensive lifestyle intervention can produce beneficial effects on body weight, HbA1c and other cardiovascular risk factors among young women with previous GDM who subsequently developed new diabetes. [ABSTRACT FROM AUTHOR]

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B12, with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes (MTHFR, MTR, and MTRR) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0. Methods: A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pairs) was organized in Tianjin, China. Additive interactions were used to test interaction effects while mediation analyses and Sobel tests were used to test mediation effects of LPC18:0 and SFA16:0 between copresence of rs7747752 and low GUDCA/DCA, and GDM risk. Results: The CDKAL1 rs7747752 was associated with GDM (P<0.05). The rs7747752 C polymorphism markedly enhanced ORs of low GUDCA from 4.04 (0.72-22.8) to 9.02 (1.63-49.7) and low DCA from 1.67 (0.68-4.11) to 4.24 (1.84-9.76), both with significant additive interactions. Further adjustment for LPC18:0 attenuated the interactive effects of rs7747752 and low DCA, with a significant mediation effect (P=0.003). High SFA16:0 did not mediate the interactive effects of rs7747752 and low DCA/GUDCA on GDM risk. Conclusions: The CDKAL1 rs7747752 C carrier status and low GUDCA/DCA had significant additive interactions on the risk of GDM with the effect from interaction with DCA being partially mediated via increasing LPC18:0. [ABSTRACT FROM AUTHOR]

Aims: Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed. Methods: We recruited 1144 mother–child pairs (572 GDM and 572 non‐GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9 years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring. Results: After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high‐density‐lipoprotein (HDL) cholesterol (1.40 ± 0.01 vs. 1.50 ± 0.01; p < 0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37 ± 0.01 vs. 0.35 ± 0.01; p < 0.05) in comparison with their counterparts born to mothers without GDM. Multivariate‐adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15–3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00–1.81) for high triglycerides/HDL cholesterol ratio, respectively. Conclusions: Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9 years old. [ABSTRACT FROM AUTHOR]

Background Interactions between genetic and nutritional factors can contribute to the risk of gestational diabetes mellitus (GDM). Objectives We aimed to explore the associations of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) single-nucleotide polymorphism (SNP) rs7747752 and serum concentrations of SFAs with the risk of GDM in Chinese women. Methods We conducted a 1:1 case–control study in a prospective cohort of pregnant women in Tianjin, China. Serum SFA data were collected from a total of 243 women with GDM and their controls matched by maternal age (±1 y). Among them, 207 case–control pairs had high-quality sequencing data. P/L and S/P ratios were defined as palmitic acid (16:0)/lauric acid (12:0) and stearic acid (18:0)/palmitic acid, respectively. Conditional logistic regression analysis was performed to estimate associations of CDKAL1 SNP rs7747752 and serum concentrations of SFAs with the risk of GDM. An additive interaction between rs7747752 and palmitic acid was analyzed to test the contribution of their interaction to the risk of GDM. Results Among the 5 tested SFAs, palmitic acid was positively whereas lauric acid was negatively associated with the risk of GDM. A P/L ratio ≥12.2 and an S/P ratio ≤0.71 were independently and synergistically associated with an increased risk of GDM. The CDKAL1 rs7747752 G > C variant was significantly associated with an increased risk of GDM (P  < 0.05). Furthermore, the presence of the rs7747752 G > C variant increased the OR (95% CI) of high palmitic acid concentration from 1.55 (0.61, 3.97) to 4.34 (2.04, 9.23), with a significant additive interaction. Conclusions The interaction between high serum palmitic acid concentration and the CDKAL1 rs7747752 G > C variant played a critical role in GDM. Given that a hypocaloric low-carbohydrate diet can lower palmitic acid concentrations, it is worthwhile to test whether such a diet is effective in reducing the risk of GDM, especially among women who have both risk factors. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to develop a machine learning–based prediction model for gestational diabetes mellitus (GDM) in early pregnancy in Chinese women. Materials and methods: We used an established population‐based prospective cohort of 19,331 pregnant women registered as pregnant before the 15th gestational week in Tianjin, China, from October 2010 to August 2012. The dataset was randomly divided into a training set (70%) and a test set (30%). Risk factors collected at registration were examined and used to construct the prediction model in the training dataset. Machine learning, that is, the extreme gradient boosting (XGBoost) method, was employed to develop the model, while a traditional logistic model was also developed for comparison purposes. In the test dataset, the performance of the developed prediction model was assessed by calibration plots for calibration and area under the receiver operating characteristic curve (AUR) for discrimination. Results: In total, 1484 (7.6%) women developed GDM. Pre‐pregnancy body mass index, maternal age, fasting plasma glucose at registration, and alanine aminotransferase were selected as risk factors. The machine learning XGBoost model‐predicted probability of GDM was similar to the observed probability in the test data set, while the logistic model tended to overestimate the risk at the highest risk level (Hosmer–Lemeshow test p value: 0.243 vs. 0.099). The XGBoost model achieved a higher AUR than the logistic model (0.742 vs. 0.663, p < 0.001). This XGBoost model was deployed through a free, publicly available software interface (https://liuhongwei.shinyapps.io/gdm%5frisk%5fcalculator/). Conclusion: The XGBoost model achieved better performance than the logistic model. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3–10 years of age in the Tianjin GDM Observational Study. Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K array) at a median age of 5.9 years (range 3.1–10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration. Results: Chronological age was positively correlated with Horvath DNAm age (r = 0.53, p < 0.0001) and Hannum DNAm age (r = 0.38, p < 0.0001). Offspring age acceleration was higher in the GDM group than non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias, p = 0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias, p < 0.0001). Increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group. Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to examine impacts of gestational diabetes mellitus (GDM) on quality of life (QoL) domains in Chinese pregnant women.Methods: We recruited 13,358 pregnant women in Tianjin, China. GDM was diagnosed using the criteria of International Association of Diabetes and Pregnancy Study Group. QoL was measured using the 36-Item Short-Form Health Survey. General linear model was used to obtain β-coefficient and 95% confidence intervals (CI) of GDM for QoL domain and summary scores.Results: 7.25% of the pregnant women developed GDM. Among the QoL domain and summary scores, only general health (GH) score was lower in the GDM group than in the non-GDM group. GDM and advanced maternal age (i.e., ≥ versus <30 years) were negatively associated with GH in multivariable analyses (β-coefficient: -1.17, 95%CI: -2.17 to -0.17 & -0.79, -1.40 to -0.18, respectively). In subgroup analyses, the β-coefficient of GDM for GH among women with maternal age ≥30 years was enhanced to -2.17 (-3.94 to -0.40) in multivariable analysis while the β-coefficient of GDM for GH among women aged <30 years was attenuated to non-significance.Conclusions: GDM and advanced maternal age were associated with reducing GH, and presence of advanced maternal age markedly increased the effect of GDM on GH. [ABSTRACT FROM AUTHOR]

Women with prior gestational diabetes mellitus (GDM) or high genetic susceptibility are prone to development of type 2 diabetes. We examined whether a lifestyle intervention modified the genetic effect on changes in glycemic markers among women with prior GDM. This study included 560 women with prior GDM from a randomized controlled trial, the Tianjin Gestational Diabetes Mellitus Prevention Program, who were assigned into an intervention arm (improved physical activity and healthy dietary intakes) or a control arm. We assessed associations of GDM related genetic variants in/near the CDKAL1 (rs7754840) and MTNR1B (rs10830962) genes with changes in fasting levels of glucose and insulin, β-cell function (HOMA-B) and insulin resistance (HOMA-IR) at 1 year and 2 years after the baseline. We found significant interactions between CDKAL1 variant rs7754840 and lifestyle intervention on changes in fasting insulin and HOMA-IR at 1 year (P for interactions = 0.008 and 0.006, respectively). The GDM-increasing C allele was associated with a 0.07-unit greater increase in fasting insulin (P = 0.048) and HOMA-IR (P = 0.045) in the control group, while opposite-directional associations were observed in the intervention group; women with the C allele seemed to decrease more in these glycemic markers than the non-C-carriers (both P ≤ 0.06). The interactions between the CDKAL1 genetic variant and lifestyle intervention on changes in fasting insulin (P = 0.035) and HOMA-IR (P = 0.024) remained significant over the 2-year period, even though the effects of lifestyle intervention were attenuated at 2-year. The MTNR1B variant rs10830962 did not show interaction with lifestyle intervention on changes in the glycemic markers. Healthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance. ClinicalTrials.gov NCT01554358. https://clinicaltrials.gov/ct2/show/NCT01554358. [ABSTRACT FROM AUTHOR]

Background Maternal metabolic abnormalities have been related to offspring obesity especially during childhood. Objectives We analyzed whether the gestational diabetes mellitus (GDM)-associated melatonin receptor 1B (MTNR1B) genotype of mothers modified the relation between maternal gestational weight gain and childhood obesity. Methods A total of 1114 Chinese mother-child pairs (mothers with or without prior GDM) were included. Mothers' MTNR1B rs10830962 genotype and gestational weight gain were assessed. Indicators of childhood obesity included BMI-for-age z -score, weight-for-age z -score, waist circumference, and body fat. Childhood overweight and obesity were also analyzed. Results We found that the maternal MTNR1B genotype significantly interacted with gestational weight gain on indicators of offspring's obesity (all P for interaction < 0.05). After multivariable adjustment, BMI-for-age z -scores associated with 1-kg gestational weight gain were 0.009 (SE 0.018), 0.026 (SE 0.010), and 0.061 (SE 0.010) in children with the maternal MTNR1B genotype CC, CG, and GG, respectively (P -interaction = 0.012). Similar interactions were observed for weight-for-age z -score, waist circumference, and body fat (P -interaction = 0.001, 0.003, and 0.012, respectively). The associations remained consistently significant in women with and without GDM. We also found significant interactions between the maternal MTNR1B genotype and gestational weight gain on the offspring's childhood overweight and obesity (P -interaction = 0.005 and 0.026, respectively). Conclusions The maternal MTNR1B genotype might interact with gestational weight gain on offspring's obesity risk during childhood. [ABSTRACT FROM AUTHOR]

Background A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM. Objective The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM. Methods We genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance. Results From baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of β cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P  = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P  = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P  = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P  = 0.03). Conclusions The exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358. [ABSTRACT FROM AUTHOR]

OBJECTIVE Several studies assessed maternal gestational diabetes mellitus (GDM) with the risk of childhood high blood pressure, and the results were inconsistent. We investigated the association between maternal GDM and hypertension risk in offspring during early childhood. METHODS We performed a large study in 1,156 mother–child pairs (578 GDM and 578 non-GDM matched by their offspring's age and sex). Maternal GDM was diagnosed according to the World Health Organization criteria. Childhood height, weight, and blood pressure were measured using standardized methods. Age-, sex-, and height-specific blood pressure Z score, childhood hypertension, and high blood pressure were evaluated according to the reference range of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. RESULTS After adjustment for maternal and children's characteristics, children born to mothers with GDM during pregnancy had higher mean values of systolic blood pressure Z score (0.09 vs. −0.17), and higher prevalence of hypertension (6.4% vs. 3.5%) and high blood pressure (15.6% vs. 9.3%) in comparison with their counterparts born to mothers without GDM during pregnancy (all P values <0.05). Multivariable-adjusted odds ratios among children of mothers with GDM compared with children of mothers without GDM were 2.32 (95% confidence intervals [CI] 1.16–4.62) for hypertension and 1.89 (95% CI 1.24–2.86) for high blood pressure, respectively. CONCLUSIONS Maternal GDM was associated with an increased risk of hypertension in the offspring. Controlling maternal GDM may be important for preventing childhood hypertension in the affected offspring. [ABSTRACT FROM AUTHOR]

Summary: Objective: Counselling patients with gestational diabetes mellitus (GDM) on their individual risk of post‐partum type 2 diabetes (T2D) is challenging. This study aimed to develop nomograms for predicting incident risk of post‐partum T2D in women with GDM diagnosed by WHO 1998 criteria. Methods: We performed a retrospective cohort study in 1263 Chinese women with GDM, of whom 83 were diagnosed as T2D at 2.3 years post‐partum. Multivariate Cox proportional hazards models were used to investigate the independent predictors for post‐partum T2D. The results of multivariate analyses were used to formulate nomograms for predicting incident risk of post‐partum T2D. The predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUROC). Results: On multivariate analysis, independent predictors of post‐partum T2DM in women with GDM included family history of diabetes [hazard ratio (HR) and its 95% confidential interval (95% CI): 2.06 (95% CI: 1.32‐3.22)], history of pregnancy‐induced hypertension [3.11 (95% CI: 1.86‐5.21)], pre‐pregnancy BMI [1.00, 1.90 (95% CI: 1.14‐3.16), and 3.67 (95% CI: 2.03‐6.63) for BMI <24, 24‐28, and ≥28 kg/m2], and 2‐hour glucose at 26‐30 gestational weeks [1.00, 2.84 (95% CI: 1.42‐5.69), and 9.42 (95% CI: 4.46‐19.90) for 2‐hour glucose at 7.8 ~ <8.5, 8.5 ~ <11.1, and ≥11.1 mmol/L). The overall AUROC of nomogram was 82.8% (95% CI: 78.1%‐87.5%), with AUROCs of 85.9% (95% CI: 79.7%‐92.1%) and 83.2% (95% CI: 77.9%‐88.6%) for post‐partum 2‐year and 3‐year risk of T2D, respectively. Conclusions: This easy‐to‐use nomogram, with non‐invasive clinical characteristics, can accurately predict the risk of post‐partum T2D in women with GDM. It may facilitate risk communication between patients and clinicians. [ABSTRACT FROM AUTHOR]

Aims: The aim was to examine associations of insulin resistance and beta cell dysfunction with macrosomia in Chinese women with gestational diabetes mellitus (GDM).Methods: We performed a secondary analysis of 923 women with GDM enrolled in a randomized controlled trial in 2010-2012 in Tianjin, China. Insulin resistance and beta-cell function were estimated using Homeostasis model assessment. Binary logistic regression was used to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). A two-step adjustment scheme was used to control for effects of potential confounders.Results: A total of 138 women (16.5%) had excessive weight gain, 127 (7.3%) had macrosomia and 150 (16.3%) had a large for gestational age (LGA) infant. Compared to women in bottom tertile of insulin resistance, women in upper tertile had increased risk of excessive weight gain (OR: 4.32, 95%CI: 1.95-9.62), macrosomia and LGA (OR: 2.61, 95%CI: 1.20-5.69; 2.75, 95%CI: 1.35-5.62, respectively). The observed overall effects were mainly due to their large effect sizes among women with normal pre-pregnancy body weight. However, beta cell function was not found to be associated with either of them.Conclusions: Increased insulin resistance during pregnancy was associated with excessive weight gain, macrosomia and LGA in Chinese women with GDM. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of the interaction between glycated haemoglobin (HbA1c) genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on long‐term glycaemic changes in the largest cohort of women with a history of gestational diabetes mellitus (GDM). Methods: This was a retrospective cohort using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Programme. A genetic risk score was established by combining 10 HbA1c‐related single‐nucleotide polymorphisms, which were identified by genome‐wide association studies. General linear regression models were applied to evaluate the effect of interaction between HbA1c genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on glycaemic changes. Results: 'A total of 1156 women with a history of GDM were included in this respective cohort study. Statistical differences in pre‐pregnancy weight, pre‐delivery weight and postpartum weight were evidenced across different groups of postpartum weight reduction. After adjusting for covariates, statistical significance for changes in HbA1c level was only observed in the postpartum weight reduction <5 kg/y group (P = 0.002), and a significant effect of interaction between HbA1c genetic risk score and postpartum weight reduction on long‐term changes in HbA1c was evidenced (P interaction = 0.01). In women with postpartum weight reduction ≥8 kg/y, those with a lower HbA1c genetic risk score had a greater decrease in HbA1c level. Conclusions: HbA1c genetic risk score interacts with postpartum weight reduction to affect long‐term changes in HbA1c levels among women with a history of GDM. [ABSTRACT FROM AUTHOR]

Background: Short height is associated with gestational diabetes mellitus (GDM) but the underlying mechanism remains unknown. This study aims to explore whether short height has a synergistic effect with pre-pregnancy overweight/obesity and undue weight gain on the risk of GDM. Methods: We recruited 19,962 singleton pregnant women from their first antenatal care visit in urban Tianjin, China, between October 2010 to August 2012. At 24–28 weeks of gestation, women underwent a 50-g 1-h glucose challenge test (GCT) followed by a 75-g 2-h oral glucose tolerance test (OGTT) if the GCT result was ≥7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut-points. Univariable and multivariable logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) analysis nested in the logistic regression analysis was used to identify a cutoff point of height for GDM. Additive interaction was used to test interactions between short height, pregnancy overweight/obesity and undue weight gain. Results: A total of 1,517 (or 7.6%) women developed GDM. The risk of GDM increased rapidly with a decreasing height from 158 cm and downwards. Using height ≥158 cm as the reference group, women with < 158 cm of height were at increased GDM risk (adjusted OR: 1.44, 95%CI: 1.18–1.75). Maternal overweight/obesity at the first antenatal care visit greatly enhanced the OR of short height for GDM (adjusted OR: 3.78, 95%CI: 2.84–5.03) with significant additive interaction (P < 0.05). However, the interaction between short height and undue weight gain was non-significant (P > 0.05). Conclusions: In Chinese pregnant women in urban Tianjin, height < 158 cm had a synergistic effect with pre-pregnancy overweight/obesity on the risk of GDM. [ABSTRACT FROM AUTHOR]

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Aims: To assess the association of uric acid (UA) with the risks of postpartum type 2 diabetes and prediabetes among women with prior gestational diabetes mellitus (GDM).Methods: We performed a cross-sectional study of 1262 GDM women at 1-5 years after delivery using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Program. Logistic regression models were used to estimate the association of different levels of serum UA with the risks of type 2 diabetes and prediabetes.Results: The multivariable-adjusted odds ratios (ORs) across quartiles of serum UA were 1.00, 1.23 (95% confidence interval [CI] 0.55-2.78), 2.05 (95% CI 0.96-4.39), and 3.17 (95% CI 1.54-6.55) (Ptrend < 0.001) for type 2 diabetes, and 1.00, 1.50 (95% CI 1.03-2.19), 2.28 (95% CI 1.58-3.30), and 2.88 (95% CI 1.99-4.17) (Ptrend < 0.001) for prediabetes, respectively. Restricted cubic splines models showed positive linear associations of serum UA as a continuous variable with the risks of type 2 diabetes and prediabetes. This positive association was significant when stratified by healthy weight and overweight participants.Conclusions: Serum UA levels have a graded positive association with the risks of type 2 diabetes and prediabetes among Chinese with a history of GDM. [ABSTRACT FROM AUTHOR]

Background: Passive smoking increased type 2 diabetes mellitus risk, but it is uncertain whether it also increased gestational diabetes mellitus (GDM) risk. We aimed to examine the association of passive smoking during pregnancy and its interaction with maternal obesity for GDM.Methods: From 2010 to 2012, 12 786 Chinese women underwent a 50-g 1-hour glucose challenge test at 24 to 28 weeks of gestation and further underwent a 75-g 2-hour oral glucose tolerance test if the glucose challenge test result was ≥7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut points. Self-reported passive smoking during pregnancy was collected by a questionnaire. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between maternal obesity and passive smoking was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Significant RERI > 0, AP > 0, or S > 1 indicated additive interaction.Results: A total of 8331 women (65.2%) were exposed to passive smoking during pregnancy. More women exposed to passive smoking developed GDM than nonexposed women (7.8% versus 6.3%, P = 0.002) with an adjusted OR of 1.29 (95%CI, 1.11 to 1.50). Compared with nonobesity and nonpassive smoking, prepregnancy obesity and passive smoking was associated with GDM risk with an adjusted OR of 3.09 (95%CI, 2.38-4.02) with significant additive interaction (P < .05 for RERI and AP).Conclusions: Passive smoking during pregnancy increased GDM risk in Chinese women independently and synergistically with prepregnancy obesity. [ABSTRACT FROM AUTHOR]

Background: The ABO blood types are associated with cancers, cardiovascular diseases and type 2 diabetes mellitus but whether they are also associated with gestational diabetes mellitus (GDM) is unknown. We examined the relationship between the ABO blood types and the risk of GDM in a prospective population-based Chinese cohort.Methods: From 2010 to 2012, we recruited 14,198 pregnant women within the first 12 weeks of gestation in Tianjin, China. All women had a glucose challenge test (GCT) at 24-28 gestational weeks, followed by a 75-g 2-h oral glucose tolerance test if the results from GCT were ≥7.8 mmol/L. GDM was diagnosed based on the glucose cut-points of the International Association of Diabetes and Pregnancy Study Group criteria. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for traditional risk factors. Stratified analysis was performed by family history of diabetes (yes versus no). Sensitivity analyses were also performed by using the World Health Organization (WHO) criteria for GDM.Results: Women with blood groups A, B or O (i.e. non-AB) were associated with increased risk of GDM as compared with those with blood group AB (adjusted OR: 1.44, 95% CI: 1.13-1.83). Sensitivity analyses showed that the result was consistent using WHO criteria. The adjusted OR of blood group non-AB versus AB for GDM was enhanced among women with a family history of diabetes (2.69, 1.21-5.96) and attenuated among those without (1.33, 1.03-1.71).Conclusions: Blood group AB was a protective factor against GDM in pregnant Chinese women. [ABSTRACT FROM AUTHOR]

Aims: To investigate the risk of postpartum metabolic syndrome in women with GDM compared with those without GDM in a Chinese population.Methods: Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM. Multivariate logistic regression was used to assess risks of postpartum metabolic syndrome between women with and without GDM. Postpartum metabolic syndrome was diagnosed by two commonly used criteria.Results: During a mean 3.53 years of follow up, 256 cases of metabolic syndrome were identified by using the NCEP ATPIII criteria and 244 cases by using the IDF criteria. Multivariable-adjusted odds ratios of metabolic syndrome in women with GDM compared with those without GDM were 3.66 (95% confidence interval [CI] 2.02-6.63) for NCEP ATPIII criteria and 3.90 (95% CI 2.13-7.14) for IDF criteria. Women with GDM had higher multivariable-adjusted odds ratios of central obesity, hypertriglyceridemia, and high blood pressure than women without GDM. The multivariable-adjusted odds ratios of low HDL cholesterol and hyperglycemia were not significant between women with and without GDM, however, the multivariable-adjusted odds ratio of hyperglycemia became significant when we used the modified criteria.Conclusions: The present study indicated that women with prior GDM had significantly higher risks for postpartum metabolic syndrome, as well as its individual components. [ABSTRACT FROM AUTHOR]

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12–3.40 & 1.95, 1.05–3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98–3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms. [Display omitted] • High serum CD44 level in early pregnancy was associated with elevated GDM risk. • High CD44 genetic variants was associated with elevated risk of GDM. • The effect of CD44 genetic variants on GDM risk was accounted for by serum CD44. [ABSTRACT FROM AUTHOR]

• Pregnancy overweight was associated with a 2.3-fold risk of macrosomia and large-for-gestational age (LGA) infants. • Gestational diabetes (GDM) and prepregnancy overweight had a synergistic effect on the risk of macrosomia and LGA. • Our findings highlight the importance to maintain normal body weight before pregnancy for perinatal health. Obesity increases risk of gestational diabetes mellitus (GDM) and GDM increases risk of macrosomia but their inter-relations for increased risk of macrosomia remain uncertain. We aimed to examine associations between prepregnancy overweight and macrosomia, and synergistic effects between prepregnancy overweight and GDM on macrosomia. From 2010 to 2012, 19,622 women in urban Tianjin, China, underwent a 50-g 1-h glucose challenge test (GCT) at 24–28 gestational weeks and followed by a 75-g 2-h oral glucose tolerance test (OGTT) if the GCT value was ≥ 7.8 mmol/L. GDM was defined according to International Association of Diabetes and Pregnancy Study Group's criteria. Overweight was defined as body mass index ≥ 24.0 kg/m2. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between prepregnancy overweight and GDM was used to test synergistic effects. In the cohort, 1791 (9.1%) and 1726 (8.8%) of the women delivered a macrosomic infant or a large-for-gestational-age (LGA) infant, respectively. Prepregnancy overweight was associated with increased risk of macrosomia and LGA with adjusted ORs being 2.29 (95%CI: 2.07–2.54) and 2.27 (2.05–2.52), respectively. Copresence of prepregnancy overweight and GDM greatly enhanced the adjusted ORs of overweight alone (ORs for macrosomia and LGA: 2.17, 1.94–2.42 & 2.21,1.98–2.47) and GDM alone (ORs for macrosomia and LGA: 2.01,1.48–2.72 & 2.14, 1.60–2.87) for macrosomia and LGA to 5.29 (4.07–6.87) for macrosomia and 4.72 (3.66–6.10) for LGA, with significant additive interactions. Prepregnancy overweight increased the risks of macrosomia and LGA independently and synergistically with GDM. [ABSTRACT FROM AUTHOR]

• High HYAL1 in early pregnancy was associated with elevated risk of GDM. • There was a significant interaction between HYAL1 and ceramide 18:0 for GDM risk. • There was a significant interaction between HYAL1 and ceramide 18:1 for GDM risk. • There was a significant interaction between HYAL1 and ceramide 24:0 for GDM risk. To explore association of serum hyaluronidase 1 (HYAL1) level in early pregnancy with gestational diabetes mellitus (GDM), and to examine interactive effects of HYAL1 with ceramides species on GDM risk. We conducted a 1:1 matched case-control study (n = 414) of pregnant women from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational weeks). Binary conditional logistic regression and restricted cubic spline (RCS) analysis were used to examine full-range risk association between HYAL1 and GDM. Additive interactions and multiplicative interactions were employed to test interactive effects of HYAL1 with ceramides species on GDM risk. Ln HYAL1 was linearly associated with GDM risk and the adjusted OR of HYAL1 ≥ vs. < its median for GDM was significant (1.65, 95%CI: 1.08–2.52). High HYAL1 markedly enhanced the ORs of high ceramide 18:0 for GDM from 2.31 (1.06–5.01) to 6.74 (2.85–16.0), and low ceramide 24:0 from 3.08 (1.33–7.11) to 8.15 (3.03–21.9), with significant additive interactions. High HYAL1 in early pregnancy may increase the risk of GDM in Chinese women, possibly via enhancing the effects of high ceramide 18:0 and low ceramide 24:0 on GDM risk. [ABSTRACT FROM AUTHOR]

Aims: To examine the association of connecting peptide (C-peptide) and the risks of postpartum diabetes and pre-diabetes among women with prior gestational diabetes.Methods: A cross-sectional study of 1263 women with prior gestational diabetes was carried out at 1-5years after delivery in Tianjin, China. Logistic regression was used to assess the associations of C-peptide and the risks of diabetes and pre-diabetes.Results: The multivariable-adjusted odds ratios based on different levels of C-peptide (0-33%, 34-66%, 67-90%, and >90% as C-peptide cutpoints) were 1.00, 1.93 (95% confidence interval [CI] 0.85-4.39), 2.49 (95% CI 1.06-5.87), and 3.88 (95% CI 1.35-11.1) for diabetes (P for trend <0.0001), and 1.00, 1.66 (95% CI 1.18-2.36), 2.38 (95% CI 1.56-3.62) and 2.35 (95% CI 1.27-4.37) for pre-diabetes (P for trend <0.0001), respectively. Restricted cubic splines models showed a positive linear association of C-peptide as a continuous variable with the risks of type 2 diabetes and pre-diabetes. The positive association was significant when stratified by healthy weight and overweight participants.Conclusions: We found a positive association between serum C-peptide levels and the risks of diabetes and pre-diabetes among Chinese women with prior gestational diabetes. Our finding suggested that elevated C-peptide levels may be a predictor of diabetes and pre-diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether lifestyle intervention can reduce type 2 diabetes risk in women with prior GDM in the Tianjin Gestational Diabetes Mellitus (GDM) Prevention Program. Methods: 1180 women who were diagnosed with GDM from 2005 to 2009 were randomly assigned to either a lifestyle intervention (n =586) or a control group (n =594). Major elements of the intervention include six face-to-face meetings with study dietitians in the first year, and two additional sessions and two telephone calls in second year. Results: During the first year, average body weight loss in the first 404 subjects was 1.40kg (2.1%) in the intervention group vs 0.21kg (0.3%) in the control group (P =0.001), and the decrease was more significant among baseline overweight women (body bass index [BMI]≥24kg/m2) in the intervention (2.91kg/4.2%) compared with that in the control group (0.51kg/0.7%) (P <0.001). In addition, women in the intervention group, compared with those in the control group, have decreased BMI, body fat, waist circumference, and plasma insulin levels, and have improved behaviors including increased leisure time activity and dietary fiber intake and decreased sedentary time and fat consumptions. Conclusion: The interim results support the efficacy and feasibility of the lifestyle intervention program. [Copyright &y& Elsevier]

Aims: To investigate the associations and predictive values of serum metabolites in early pregnancy for later development of gestational diabetes mellitus (GDM), and further explore their metabolic pathways to GDM.Methods: We conducted a 1:1 nested case-control study including 486 pregnant women from Tianjin, China, and collected blood samples at their first registration (median at 10th gestational week). Liquid chromatography-tandem mass spectrometry was used to measure serum metabolites. Orthogonal partial least squares discriminant analysis was used to select specific metabolites associated with GDM, and pathway analysis was used to identify the metabolic pathways related to GDM.Results: A total of 64 serum metabolites were included in this analysis, 17 of which were identified as specific metabolites associated with GDM. Ten metabolites increased and seven metabolites decreased GDM risk. Inclusion of these specific metabolites to the model of traditional risk factors greatly increased the predictive value from 0.69 (95% confidence interval: 0.64-0.74) to 0.92 (0.90-0.95). In addition, we found that glycerophospholipid metabolism, sphingolipid metabolism and primary bile acid biosynthesis were main metabolic pathways related to GDM.Conclusion: We identified a set of serum metabolites and their metabolic pathways in early pregnancy associated with GDM, which provided a theoretical basis for further research on the molecular pathways to GDM and early identification of GDM. [ABSTRACT FROM AUTHOR]

Aims: To explore associations between ceramides in early pregnancy and gestational diabetes mellitus (GDM); and interactions between ceramides and trimethylamine N-oxide (TMAO) metabolites for GDM.Methods: We organized a 1:1 nested case-control study (n = 486) from a prospective cohort of pregnant women. Conditional logistic regression and additive interaction were performed to examine relationships between ceramides and TMAO metabolites for GDM. We defined trimethylamine (TMA) conversion ratio (TMAR) as TMA/its precursors and TMAO conversion ratio (TMAOR) as TMAO/TMA. Copresence of high TMAR and low TMAOR indicated TMA accumulation status.Results: High ceramides 18:0 (per SD), 18:1 (per SD) and low ceramide 24:0 (≤ 3.60 nmol/mL) were associated with increased GDM risk (OR: 1.69, 1.72 & 3.59, respectively). High TMA enhanced the OR of low ceramide 24:0 for GDM from 1.53 (95%CI: 0.88-2.66) to 10.3 (2.83-37.5), high TMAR enhanced it from 1.31 (0.67-2.56) to 24.3 (6.57-89.5) and TMA accumulation enhanced it from 1.42 (0.72-2.77) to 25.5 (6.80-95.7), with all additive interactions being significant. However, the interactions between high ceramide 18 and TMAO metabolites were not significant.Conclusions: High ceramides 18:0, 18:1 and low ceramide 24:0 in early pregnancy were associated with increased GDM risk. Notably, TMA accumulation greatly amplified the risk-promoting effect of low ceramide 24:0 for GDM. [ABSTRACT FROM AUTHOR]