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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., (© 2023 John Wiley & Sons Ltd.)

Background/objective: Previous studies found conflicting results on the association between maternal gestational diabetes mellitus (GDM) and childhood overweight/obesity. This study was to assess the association between maternal GDM and offspring's adiposity risk from 6 to 8 years of age., Methods: The present study longitudinally followed 1156 mother-child pairs (578 GDM and 578 non-GDM) at 5.9 ± 1.2 years postpartum and retained 912 mother-child pairs (486 GDM and 426 non-GDM) at 8.3 ± 1.6 years postpartum. Childhood body mass index (BMI), waist circumference, body fat and skinfold were measured using standardized methods., Results: Compared with the counterparts born to mothers with normal glucose during pregnancy, children born to mothers with GDM during pregnancy had higher mean values of adiposity indicators (waist circumference, body fat, subscapular skinfold and suprailiac skinfold) at 5.9 and 8.3 years of age. There was a positive association of maternal GDM with changes of childhood adiposity indicators from the 5.9-year to 8.3-year visit, and β values were significantly larger than zero: +0.10 (95% CI: 0.02-0.18) for z score of BMI for age, +1.46 (95% CI: 0.70-2.22) cm for waist circumference, +1.78% (95% CI: 1.16%-2.40%) for body fat, +2.40 (95% CI: 1.78-3.01) mm for triceps skinfold, +1.59 (95% CI: 1.10-2.09) mm for subscapular skinfold, and +2.03 (95% CI: 1.35-2.71) mm for suprailiac skinfold, respectively. Maternal GDM was associated with higher risks of childhood overweight/obesity, central obesity, and high body fat (Odd ratios 1.41-1.57 at 5.9 years of age and 1.73-2.03 at 8.3 years of age) compared with the children of mothers without GDM., Conclusions: Maternal GDM was a risk factor of childhood overweight/obesity at both 5.9 and 8.3 years of age, which was independent from several important confounders including maternal pre-pregnancy BMI, gestational weight gain, children's birth weight and lifestyle factors. This significant and positive association became stronger with age., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

To evaluate the independent association of seasonal variation with GDM incidence in Tianjin, China, and to test whether there is an additive interaction between seasonal variation and pre-pregnancy body mass index (BMI) on GDM incidence. A population-based observational cohort study was conducted using the healthcare records data from Tianjin, China. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between pre-pregnancy BMI groups and seasons was estimated by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Among the 112,639 pregnant women, 20.8% developed GDM at 24-28 weeks of gestation. The multivariable adjusted ORs and 95% CIs were 1.00, 1.00 (0.96-1.05), 1.15 (1.09-1.20) and 1.22 (1.16-1.29) respectively based on seasons (spring, summer, autumn and winter). Compared with the spring/summer and pre-pregnant BMI < 24 kg/m 2 group, co-presence of autumn/winter and pre-pregnancy BMI ≥ 24 kg/m 2 increased the OR from 1.00 to 2.70 (95% CI 2.28-3.20), with a significant additive interaction: RERI (0.32, 95% CI 0.19-0.45), S (1.21, 95% CI 1.12-1.31) and AP (0.11, 95% CI 0.07-0.16). Autumn/winter is an independent risk factor for GDM incidence, and can significantly amplify the obesity-associated risk for GDM incidence. The underlying mechanism warrants further investigations. We suggest that seasonality is an additional factor when interpreting OGTT results for the diagnosis of GDM., (© 2023. The Author(s).)

Aims: This study aimed to explore associations of mannan-binding lectin-associated serine protease (MASP) levels in early pregnancy with gestational diabetes mellitus (GDM). We also examined interactions of MASPs and deoxycholic acid (DCA)/glycoursodeoxycholic acid (GUDCA) for the GDM risk and whether the interactive effects if any on the GDM risk were mediated via lysophosphatidylcholine (LPC) 18:0., Materials and Methods: A 1:1 case-control study (n = 414) nested in a prospective cohort of pregnant women was conducted in Tianjin, China. Binary conditional logistic regressions were performed to examine associations of MASPs with the GDM risk. Additive interaction measures were used to examine interactions between MASPs and DCA/GUDCA for the GDM risk. Mediation analyses and Sobel tests were used to examine mediation effects of LPC18:0 between the copresence of MASPs and DCA/GUDCA on the GDM risk., Results: High MASP-2 was independently associated with GDM [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.44-4.77], while the effect of high MASP-1 on GDM was attributable to high MASP-2 ( P for Sobel test: 0.003). Low DCA markedly increased the OR of high MASP-2 alone from 2.53 (1.10-5.85) up to 10.6 (4.22-26.4), with a significant additive interaction. In addition, high LPC18:0 played a significant mediating role in the links from low DCA to GDM and from the copresence of high MASP-2 and low DCA to GDM ( P for Sobel test <0.001) but not in the link from high MASP-2 to GDM., Conclusions: High MASP-1 and MASP-2 in early pregnancy were associated with GDM in Chinese pregnant women. MASP-2 amplifies the risk of low DCA for GDM, which is mediated via LPC18:0., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Li, Zhang, Li, Li, Zhang, Wang, Wang, Fang, Yu, Hu, Leng and Yang.)

Background and Aims: 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., Materials and Methods: 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 10 th 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2022 World Obesity Federation.)

Aims: 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)., Methods: 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., Results: 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)., Conclusions: Parental prepregnancy obesity predicted offspring overweight before two years of age among children of Chinese women with GDM., Competing Interests: Declaration of Competing Interest All authors declared no conflict of interest., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

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.

Objective: We aimed to explore associations of branched-chain amino acids (BCAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high BCAAs and lipidomics markers had interactive effects on the risk of GDM., Methods: We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women in Tianjin, China. Blood samples were collected at their first antenatal care visit (median 10 gestational weeks). Serum BCAAs, saturated fatty acids (SFA) and lysophosphatidylcholines (LPC) were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional logistic regression was performed to examine associations of BCAAs with the risk of GDM. Interactions between high BCAAs and high SFA16:0 for GDM were examined using additive interaction measures., Results: High serum valine, leucine, isoleucine, and total BCAAs were associated with markedly increased risk of GDM (OR of top vs bottom tertiles: 1.91 [95% CI, 1.22-3.01]; 1.87 [1.20-2.91]; 2.23 [1.41-3.52]; 1.93 [1.23-3.02], respectively). The presence of high SFA16:0 defined as ≥ 17.1 nmol/mL (ie, median) markedly increased the ORs of high leucine alone and high isoleucine alone up to 4.56 (2.37-8.75) and 4.41 (2.30-8.43) for the risk of GDM, with significant additive interaction. After adjustment for LPCs, the ORs were greatly elevated (6.33, 2.25-17.80 and 6.53, 2.39-17.86) and the additive interactions became more significant., Conclusion: BCAAs in early pregnancy were positively associated with the risk of GDM, and high levels of leucine and isoleucine enhanced the risk association of high SFA16:0 with GDM, independent of LPCs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gestational diabetes mellitus (GDM) is associated with adverse health consequences for women and their offspring. It is associated with maternal body mass index (BMI) and may be associated with gestational weight gain (GWG). But due to the heterogeneity of diagnosis and treatment and the potential effect of GDM treatment on GWG, the association between the two has not been thoroughly clarified. Compared to body weight, BMI has the advantage that it considers height during the whole course of pregnancy. Understanding BMI changes during pregnancy may provide new evidence for the prevention of GDM., Methods: This study investigated the BMI change of pregnant women based on a retrospective study covering all communities in Tianjin, China. According to the results of GDM screening at 24-28 weeks of gestation, pregnancies were divided into the GDM group and the non-GDM group. We compared gestational BMI change and GWG in the two groups from early pregnancy to GDM screening. GWG was evaluated according to the IOM guidelines. Logistic regression was applied to determine the significance of variables with GDM., Results: A total of 41,845 pregnant women were included in the final analysis (GDM group, n = 4257 vs. non-GDM group, n = 37,588). BMI gain has no significant differences between the GDM and non-GDM groups at any early pregnancy BMI categories (each of 2 kg/m 2 ), as well as weight gain (P > 0.05). Early pregnancy BMI was a risk factor for GDM (OR 1.131, 95% CI 1.122-1.139). And BMI gain was associated with a decreased risk of GDM in unadjusted univariate analysis (OR 0.895, 95% CI 0.869-0.922). After adjusting on early pregnancy BMI and other confounding factors, the effect of BMI gain was no longer significant (AOR 1.029, 95% CI 0.999-1.061), as well as weight gain (AOR 1.006, 95% CI 0.995-1.018) and GWG categories (insufficient: AOR 1.016, 95% CI 0.911-1.133; excessive: AOR 1.044, 95% CI 0.957-1.138)., Conclusions: BMI in early pregnancy was a risk factor for GDM, while BMI gain before GDM screening was not associated with the risk of GDM. Therefore, the optimal BMI in early pregnancy is the key to preventing GDM., (© 2022. The Author(s).)

Aims: To explore associations between adverse pregnancy outcomes and risk of postpartum diabetes and prediabetes among Chinese women with gestational diabetes mellitus (GDM)., Methods: A total of 507 women with GDM who participated in a randomized controlled trial were successfully followed up at a median of 9.1  (interquartile range: 7.7-11.3) weeks after delivery and underwent a 75 g 2-h oral glucose tolerance test. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group's criteria. Postpartum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of adverse pregnancy outcomes for postpartum diabetes, prediabetes and abnormal glucose regulation (AGR)., Results: Of 507 women with GDM, 3.7% (19) women developed postpartum diabetes, 35.1% (178) women developed postpartum prediabetes. Preterm birth was associated with increased risk of postpartum prediabetes and AGR (adjusted OR: 3.24, 95%CI: 1.48-7.07 & 3.16, 1.46-6.85). Low birth weight was associated with the risk of postpartum prediabetes, diabetes and AGR (adjusted OR: 2.78, 95%CI: 1.13-6.86; 5.21, 1.13-24.02 & 2.99, 1.24-7.21)., Conclusions: Preterm birth and low birth weight were predictive of postpartum prediabetes, diabetes or AGR in Chinese women with GDM., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B 12 , 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 B 12 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 B 12 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 B 12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B 12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Leng, Li, Liu, Yan, Yu, Hu, Ma, Fang, Wang and Yang.)

Aims/introduction: We investigated the association between leukocyte counts and glucose challenge test (GCT) level during pregnancy., Materials and Methods: We collected prenatal information of women who had their first clinic visit in early pregnancy. Women underwent GCT at 24-28 gestational weeks, and a result of ≥7.8 mmol/L was considered positive. Participants were divided into quartiles of leukocyte counts, and association with GCT results and positive rate were analyzed by logistic regression., Results: Among 20,707 pregnant women, the median of leukocyte counts was higher in the positive group than the normal group (8.5 × 10 9 /L vs 8.2 × 10 9 /L, P < 0.01). There was a linear trend in GCT results and positive rate with increasing leukocyte quartiles. Compared with the lowest quartile, the highest leukocyte quartile (>9.70 × 10 9 /L) was significantly associated with positive GCT results (adjusted odds ratio 1.378, 95% confidence interval 1.246-1.524), and the linear relationship between increased risk of positive result and increasing leukocyte quartiles persisted (P for linear trend <0.01). In multivariable analysis, the risk of a positive result increased by 2.2% with each 1-unit increase in leukocyte counts (adjusted odds ratio 1.022, 95% confidence interval 1.011-1.033)., Conclusions: Elevated leukocyte counts in early pregnancy were independently and linearly associated with the risk of positive GCT levels, indicating that inflammation might play an important role in the development of gestational diabetes mellitus., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Aims: This study tests whether cut-off points of the International Association of Diabetes and Pregnancy Study Group's (IADPSG) criteria had threshold effects on post-partum prediabetes and diabetes among Chinese pregnant women with gestational diabetes mellitus (GDM)., Materials and Methods: A total of 507 out of 1000 women with GDM (948 of them enrolled in a lifestyle trial during pregnancy) turned up for the follow-up study and underwent a 75-g 2-h oral glucose tolerance test. GDM was diagnosed based on the IADPSG's criteria while post-partum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of fasting, 1-h and 2-h plasma glucoses (PGs) for post-partum diabetes and prediabetes. Restricted cubic spline was used to identify any threshold effects., Results: At a median of 9.1 weeks post-partum, 3.7% (n = 19) women developed post-partum diabetes and 35.1% (n = 178) developed post-partum prediabetes. Fasting PG ≥ 5.1 mmol/L was associated with markedly increased risk of post-partum diabetes without a discernible threshold (adjusted OR: 3.87, 95% CI: 1.03-14.52) while 2-h PG ≥ 8.5 and ≥ 9.0 mmol/L had threshold effects on post-partum prediabetes (2.10, 1.33-3.30) and diabetes (4.02, 1.04-15.56). The 1-h PG also had a threshold at ≥10.0 mmol/L for prediabetes (1.67, 1.06-2.64), but it was not significant for post-partum diabetes., Conclusions: Among Chinese women with GDM, fasting PG ≥ 5.1 mmol/L was associated with post-partum diabetes without any discernible threshold effects while 2-h PG ≥ 8.5 and ≥ 9.0 mmol/L respectively identified women at high risk of post-partum prediabetes and diabetes., (© 2021 John Wiley & Sons Ltd.)

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., (© 2021 Diabetes UK.)

Introduction: To investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM)., Research Design and Methods: We organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM., Results: We found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=-0.177 (0.048); p=2.66×10 -4 ). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p = 0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p = 0.018), compared with those with low IR-GRS and high TCDCA., Conclusions: Genetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes IGF1 , IGF2 , H19 , ARHGRF11 , MEST , NR3C1 , ADIPOQ  and RETN . Materials & methods: A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST ); two (cg19466922 in MEST and cg26263166 in IGF2 ) were associated at p < 0.05 but mediated 26 and 13%, respectively. Conclusion: MEST and IGF2 were previously identified for potential involvement in fetal growth and development (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).

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&#95;risk&#95;calculator/)., Conclusion: The XGBoost model achieved better performance than the logistic model., (© 2020 John Wiley & Sons Ltd.)

Background: Gestational diabetes mellitus (GDM) is a major macrosomia risk factor. Variations in the catechol- O -methyltransferase (COMT; rs4680) genotypes are associated with heightened susceptibility to environmental exposures and nutritional conditions. However, macrosomia risks associated with COMT genetics, epigenetics, and the interaction between genetic and epigenetics among children with and without exposure to GDM are unknown. Methods: Data from women/children pairs ( n  = 1087) who participated in the Tianjin Gestational Diabetes Birth Cohort were used to examine the odds of being born with macrosomia associated with COMT-genotypes, 55 CpG sites located on the COMT gene, and genetic and epigenetic interactions. Odds of macrosomia associated with COMT genetic, epigenetic, genetic and epigenetic interactions, and moderations with GDM were tested using adjusted logistic regression models. Results: Overall, 16.1% ( n  = 175) of children were born with macrosomia. Models showed that children with at least one copy of the minor allele (A) had higher odds of macrosomia (odds ratio, 1.82; 95% confidence interval 1.25-2.64) compared with children with the GG-genotype. After false discovery rate corrections, none of the 55 CpG sites located on the COMT gene was associated with odds of macrosomia. The genetic and epigenetic associations were not modified by exposure to GDM. Conclusion: Findings suggest carriers of the COMT GG-genotype had lower odds of macrosomia, and this association was not modified by epigenetics or exposure to GDM.

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 (TMA R ) as TMA/its precursors and TMAO conversion ratio (TMAO R ) as TMAO/TMA. Copresence of high TMA R and low TMAO R 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 TMA R 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to estimate the associations of genetically determined maternal blood glucose levels with obesity-related outcomes among children from pregnancies with and without gestational diabetes mellitus (GDM)., Methods: A total of 1,114 mothers with (N = 560) and without (N = 554) GDM and their children were included in the present study. A maternal genetic risk score (GRS) for blood glucose was constructed on the basis of 17 single-nucleotide polymorphisms identified from a recent genome-wide association study., Results: It was found that maternal GRS for blood glucose showed different associations with offspring risk of overweight and obesity, as well as adiposity measures (all P for interaction  < 0.05). Among mothers without GDM, genetically determined maternal blood glucose levels were associated with an 89% higher risk of overweight in their children (95% CI: 42%-152% per SD increase in GRS, P = 1.40 × 10 -5 ) and a 120% higher risk of obesity (44%-235%, P = 2.61 × 10 -4 ) after adjustment for covariates. In addition, higher maternal GRS for blood glucose was associated with children's increased obesity-related traits (all P < 0.05). However, no significant associations were observed among children of mothers with GDM., Conclusions: This study indicates that GDM status may modify the relation between genetically determined glucose levels and obesity risk among children., (© 2020 The Obesity Society.)

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.

Objective: To analyze the interactions between maternal gestational diabetes mellitus (GDM) and genetically determined maternal body mass index (BMI) during pregnancy on offspring childhood obesity., Research Design and Methods: A total of 1114 Chinese mother-child pairs (560 GDM and 554 non-GDM) were included between August 2009 and July 2011. Maternal genetic risk score (GRS) of BMI during pregnancy was derived on the basis of 12 single nucleotide polymorphisms identified from a genome-wide association study. Offspring's BMI, BMI-for-age z score, weight, weight-for-age z score, waist circumference, sum of skinfolds, and body fat percentage during childhood were measured or calculated., Results: Maternal GRS of BMI during pregnancy significantly interacted with maternal GDM status on childhood risks of overweight and obesity (all P for interaction <.05). After multivariable adjustment, per unit of GRS was associated with a 24% (P<.001) and a 28% (P<.001) increased risk of overweight and obesity among children of GDM mothers, whereas no significant associations were observed among children of mothers without GDM. In addition, per unit GRS of BMI during pregnancy was significantly associated with 0.16 kg/m 2 higher BMI (P=.002), 0.09 higher BMI-for-age z score (P=.002), 0.24 kg higher weight (P=.04), 0.06 higher weight-for-age z score (P=.02), 0.28 cm higher waist circumference (P=.03), 0.94 mm higher sum of skinfolds (P=.004), and 0.37% higher body fat percentage (P=.03) among children of GDM mothers. There were no significant associations between maternal GRS of BMI during pregnancy and offspring's obesity-related outcomes among children of mothers without GDM., Conclusion: Our findings for the first time indicate that maternal GDM status may modify the relation between genetically determined maternal BMI during pregnancy and offspring's obesity risk during childhood., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

This study assessed within-trial cost-effectiveness of a shared care program (SC, n = 339) for pregnancy outcomes compared to usual care (UC, n = 361), as implemented in a randomized trial of Chinese women with gestational diabetes (GDM). SC consisted of an individualized dietary advice and physical activity counseling program. The UC was a one-time group education program. The effectiveness was measured by number needed to treat (NNT) to prevent one macrosomia/large for gestational age (LGA) infant. The cost-effectiveness was measured by incremental cost-effectiveness ratio in terms of cost (2012 Chinese Yuan/US dollar) per case of macrosomia and LGA prevented. The study took both a health care system and a societal perspective. This study found that the NNT was 16/14 for macrosomia/LGA. The incremental cost for treating a pregnant woman was ¥1,877 ($298) from a health care system perspective and ¥2,056 ($327) from a societal perspective. The cost of preventing a case of macrosomia/LGA from the two corresponding perspectives were ¥30,032/¥26,278 ($4,775/$4,178) and ¥32,896/¥28,784 ($5,230/$4,577), respectively. Considering the potential severe adverse health and economic consequences of a macrosomia/LGA infant, our findings suggest that implementing this lifestyle intervention for women with GDM is an efficient use of health care resources., Competing Interests: Lilly Diabetes is a commercial source, but this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: 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., Research Design and Methods: 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., Results: 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., Conclusions: Healthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance., Trial Registration Number: ClinicalTrials.gov NCT01554358. URL OF REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01554358., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: This 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., Design: We 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., Results: Of 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., Conclusions: LPCs 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., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To develop and validate a set of risk scores for the prediction of gestational diabetes mellitus (GDM) before the 15th gestational week using an established population-based prospective cohort., Methods: From October 2010 to August 2012, 19 331 eligible pregnant women were registered in the three-tiered antenatal care network in Tianjin, China, to receive their antenatal care and a two-step GDM screening. The whole dataset was randomly divided into a training dataset (for development of the risk score) and a test dataset (for validation of performance of the risk score). Logistic regression was performed to obtain coefficients of selected predictors for GDM in the training dataset. Calibration was estimated using Hosmer-Lemeshow test, while discrimination was checked using area under the receiver operating characteristic curve (AUC) in the test dataset., Results: In the training dataset (total=12 887, GDM=979 or 7.6%), two risk scores were developed, one only including predictors collected at the first antenatal care visit for early prediction of GDM, like maternal age, body mass index, height, family history of diabetes, systolic blood pressure, and alanine aminotransferase; and the other also including predictors collected during pregnancy, that is, at the time of GDM screening, like physical activity, sitting time at home, passive smoking, and weight gain, for maximum performance. In the test dataset (total=6444, GDM=506 or 7.9%), the calibrations of both risk scores were acceptable (both p for Hosmer-Lemeshow test >0.25). The AUCs of the first and second risk scores were 0.710 (95% CI: 0.680 to 0.741) and 0.712 (95% CI: 0.682 to 0.743), respectively (p for difference: 0.9273)., Conclusion: Both developed risk scores had adequate performance for the prediction of GDM in Chinese pregnant women in Tianjin, China. Further validations are needed to evaluate their performance in other populations and using different methods to identify GDM cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Abdominal obesity is more closely associated with diabetes than general obesity in adults, however, it is unknown which kind of obesity is more closely associated with abnormal glucose metabolism in children., Research Design and Methods: We recruited 973 children (aged 3.08±1.06) of mothers with prior gestational diabetes mellitus (GDM). Children's height, weight, waist circumstance, fasting glucose and insulin were measured using standardized methods. Logistic regression models were used to assess the single and joint associations of general and abdominal obesity with the risks of hyperglycemia (the upper quartile of fasting glucose), insulin resistance (the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR)), and β-cell dysfunction (the lower quartile of HOMA-%β)., Results: Compared with normal weight children, children with general overweight/obesity had higher levels of HOMA-IR and HOMA-%β, higher ORs for hyperglycemia (1.56, 95% CI 1.06 to 2.30) and insulin resistance (3.44, 95% CI 2.32 to 5.09), but a lower OR for β-cell dysfunction (0.65, 95% CI 0.41 to 1.04). Children with abdominal obesity had an increased risk of insulin resistance (2.54, 95% CI 1.71 to 3.76) but not hyperglycemia and β-cell dysfunction compared with children with normal waist circumstance. In the joint analyses, general overweight children with and without abdominal obesity had an increased risk of hyperglycemia and insulin resistance compared with normal weight children., Conclusions: General obesity was more closely associated with abnormal glucose metabolism than abdominal obesity in children of mothers with GDM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The aim of the present study was to investigate the race-specific association between a history of gestational diabetes mellitus (GDM) and incidence of type 2 diabetes and evaluate how the risk changed over different years after delivery., Methods: We performed two large cohorts - the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and the Tianjin GDM Observational Study. The multivariate cox regression model was used to assess the risk of incident postpartum diabetes between women with and without prior GDM., Results: During a mean follow-up of 13.8 years, 405 women developed type 2 diabetes. After adjustment for multiple confounding factors, Chinese women with GDM had a higher risk of incident diabetes within 5 years postpartum than African Americans with GDM compared with Chinese and African Americans without GDM (Hazard ratio 71.5 in Chinese vs. 9.29 in African Americans). When the risk of incident diabetes was analyzed within 10 years, white women with GDM seemed to have a higher hazard ratio than African American and Chinese women with GDM compared with non-GDM women of different races. In comparison to African American women without GDM, the highest risk of type 2 diabetes over 10 years postpartum appeared in Chinese women with GDM, followed by African American women with GDM, and the smallest risk was seen in white women with GDM., Conclusions: Different genetic backgrounds and other risk factors among women of different races might contribute to the racial differences in the incidence of diabetes postpartum among women with GDM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM)., Design: A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO., Results: TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant., Conclusions: TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM., (Copyright © 2019 Endocrine Society.)

Objective: To evaluate the independent or combined effects of gestational diabetes (GDM) and pre-pregnancy and postpartum BMI on the odds of postpartum diabetes and hyperglycemia., Methods: The study samples included 1263 women with prior GDM and 705 women without GDM. Postpartum 1-7 years diabetes was diagnosed by the standard oral glucose tolerance test., Results: The multivariable-adjusted odds ratios among women with prior GDM, compared with those without it, were 7.52 for diabetes and 2.27 for hyperglycemia. The multivariable-adjusted odds ratios at different postpartum BMI levels (<24, 24-27.9, and ≥ 28 kg/m 2 ) were 1.00, 2.80, and 8.08 for diabetes (P trend  < 0.001), and 1.00, 2.10, and 4.42 for hyperglycemia (P trend  < 0.001), respectively. Women with high body fat (≥31.9%) or abdominal obesity (≥85 cm) had a 2.7-6.9-fold higher odds ratio for diabetes or hyperglycemia. Women with both obesity and prior GDM had the highest risk of diabetes or hyperglycemia compared with non-obese women without GDM. Non-obese women with prior GDM had the same risk of diabetes and hyperglycemia as non-GDM women with obesity. When using Cox regression models, the results were very close to those using logistic regression models., Conclusions: Maternal prior GDM and pre-pregnancy or postpartum obesity contribute equally to postpartum diabetes and hyperglycemia risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © American Society for Nutrition 2019.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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/m 2 ], 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., (© 2018 John Wiley & Sons Ltd.)

Objective: To investigate the association of lactation intensity and duration with postpartum diabetes and prediabetes risks among Chinese women with a history of gestational diabetes (GDM)., Methods: We included 1260 women with a history of GDM who participated in the whole population's GDM universal screening survey by using the 1999 World Health Organization's criteria. Lactation intensity and lactation duration were collected by a standardized questionnaire. Postpartum diabetes and prediabetes risk were confirmed by an oral glucose tolerance test., Results: During a mean postpartum period of 3.65 years, we identified 114 cases of diabetes and 417 cases of prediabetes. The multivariable-adjusted hazard ratios based on different lactation intensity (exclusive formula, mixed feeding, and exclusive lactation) were 1.00, 0.68, 0.45 for diabetes (P trend  = 0.008), and 1.00, 0.74, and 0.61 for prediabetes (P trend  = 0.006), respectively. The multivariable-adjusted hazard ratios associated with different lactation duration (none, 0-6 months, 6-12 months, 12-18 months, and ≥18 months) were 1.00, 0.66, 0.42, 0.66, and 0.25 for diabetes (P trend  = 0.013), and 1.00, 0.82, 0.62, 0.67, and 0.63 for prediabetes (P trend  = 0.021), respectively. A restricted cubic spline curve showed a graded inverse association of lactation duration with the risks of diabetes and prediabetes (P trend  < 0.001)., Conclusions: Higher-lactation intensity and longer-lactation duration were significantly associated with lower risks of postpartum diabetes and prediabetes among Chinese women with a history of GDM., (© 2018 John Wiley & Sons, Ltd.)

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., (© 2018 John Wiley & Sons Ltd.)

Aims: To examine associations between the indicators of socio-economic status (SES) and gestational diabetes mellitus (GDM)., Methods: From 2010 to 2012, 17 659 women underwent glucose challenge test (GCT) and oral glucose tolerance test if GCT ≥ 7.8 mmol/L at 24-28 gestational weeks in 6 urban districts of Tianjin, China. Binary logistic regression was used to obtain adjusted odds ratio (OR) of SES for GDM, as defined by education attainment and family monthly income., Results: A total of 1264 women (7.2%) were found to have GDM. If the women with low-middle income and high school or below used as the reference group, the middle-high income group and the high income group were associated with decreased risks of GDM (OR: 0.85, 95%CI: 0.71-1.00 & 0.80, 0.65-0.98) while tertiary education attainment was associated with decreased risk of GDM (0.75, 0.58-0.97). Women with higher income and/or higher education attainment tended to have a decreased risk of GDM (P for trend: 0.0105). All these significant ORs were attenuated to be non-significant by adjustment for pre-pregnancy body mass index (BMI), but not by adjustment for gestational weight gain (GWG)., Conclusions: In urban Tianjin, indicators of high SES were associated with decreased risk of GDM via decreased pre-pregnancy BMI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To compare risks of early postpartum diabetes and prediabetes in Chinese women with and without gestational diabetes mellitus (GDM) during pregnancy., Subjects and Methods: Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM who participated in the urban GDM universal screening survey by using World Health Organization's criteria. Postpartum diabetes and prediabetes were identified after a standard oral glucose tolerance test. Cox proportional hazards regression was used to assess risks of postpartum diabetes and prediabetes between women with and without GDM., Results: During a mean follow-up of 3.53 years postpartum, 90 incident cases of diabetes and 599 incident cases of prediabetes were identified. Multivariable-adjusted hazard ratios among women with prior GDM, compared with those without it, were 76.1 (95% CI: 23.6-246) for diabetes and 25.4 (95% CI: 18.2-35.3) for prediabetes. When the mean follow-up extended to 4.40 years, 121 diabetes and 616 prediabetes cases were identified. Women with prior GDM had a 13.0-fold multivariable-adjusted risk (95% CI: 5.54-30.6) for diabetes and 2.15-fold risk (95% CI: 1.76-2.62) for prediabetes compared with women without GDM. The positive associations between GDM and the risks of postpartum diabetes and prediabetes were significant and persistent when stratified by younger and older than 30 years at delivery and normal weight and overweight participants., Conclusions: The present study indicated that women with prior GDM had significantly increased risks for postpartum diabetes and prediabetes, with the highest risk at the first 3-4 years after delivery, compared with those without GDM., (© 2018 European Society of Endocrinology.)

Context: Disturbed circadian rhythms and sleep quality during pregnancy have been related to gestational weight gain and gestational diabetes mellitus (GDM), which affect postpartum glucose metabolism and future risk of type 2 diabetes., Objective: We assessed whether the circadian rhythm-related melatonin receptor 1B (MTNR1B) genotype was associated with 1 to 5 years of postpartum glycemic changes among women with a history of GDM and whether gestational weight gain modified such associations., Design, Settings, and Participants: The established circadian rhythm-associated MTNR1B genetic variant (rs10830963) was genotyped in 1025 Chinese women with a history of GDM. Body weight and glycemic traits, during and after pregnancy, were longitudinally collected., Main Outcome Measures: The main outcome measure was postpartum glycemic changes., Results: We found that women carrying different MTNR1B genotypes showed distinct postpartum changes in 2-hour oral glucose tolerance test: 0.36, 0.20, and -0.19 mM per additional copy of the shorter sleep duration-related G allele in women with inadequate, adequate, and excessive gestational weight gain, respectively (for interaction, P = 0.028). The corresponding changes in fasting glucose were 0.14, 0.13, and 0.01 mM, although the modification effect of gestational weight gain on the genetic association was marginally significant (for interaction, P = 0.067)., Conclusions: Our findings suggest that gestational weight gain may modify the circadian rhythm-related MTNR1B genetic variant on long-term glycemic changes, highlighting the significance of gestational weight management in diabetes prevention among women with GDM.

Aims: To report the weight loss findings after the first year of a lifestyle intervention trial among women with gestational diabetes mellitus (GDM)., Methods: A total of 1180 women with GDM were randomly assigned (1:1) to receive a 4-year lifestyle intervention (intervention group, n = 586) or standard care (control group, n = 594) between August 2009 and July 2011. Major elements of the intervention included 6 face-to-face sessions with study dieticians and two telephone calls in the first year, and two individual sessions and two telephone calls in each subsequent year., Results: Among 79% of participants who completed the year 1 trial, mean weight loss was 0.82 kg (1.12% of initial weight) in the intervention group and 0.09 kg (0.03% of initial weight) in the control group (P = .001). In a prespecified subgroup analysis of people who completed the trial, weight loss was more pronounced in women who were overweight (body mass index ≥24 kg/m 2 ) at baseline: mean weight loss 2.01 kg (2.87% of initial weight) in the intervention group and 0.44 kg (0.52% of initial weight) in the control group (P < .001). Compared with those in the control group, women in the intervention group had a greater decrease in waist circumference (1.76 cm vs 0.73 cm; P = .003) and body fat (0.50% vs 0.05% increase; P = .001)., Conclusion: The 1-year lifestyle intervention led to significant weight losses after delivery in women who had GDM, and the effect was more pronounced in women who were overweight at baseline., (© 2018 John Wiley & Sons Ltd.)

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) (P trend  < 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) (P trend  < 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)