Aromatic Amino Acids and Their Interactions with Gut Microbiota-Related Metabolites for Risk of Gestational Diabetes: A Prospective Nested Case-Control Study in a Chinese Cohort.

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.

GIPC2 is a tumor suppressor gene for acute myeloid leukemia and induces apoptosis of leukemia cells by regulating the PI3K/AKT pathway.

Aims: To explore the expression and methylation levels of GIPC2 in acute myeloid leukemia (AML), discuss the mechanism of GIPC2 in AML and provide new strategies for the diagnosis and treatment of AML. Methods: qPCR, western blotting, cell counting kit-8 assay, bisulfite sequencing and other experiments were used in this study. Results: The expression of GIPC2 was found to be downregulated in AML and is mainly affected by DNA promoter methylation. Decitabine can demethylate the promoter region of GIPC2, and GIPC2 expression is upregulated after demethylation. Overexpression of GIPC2 in HL-60 cells can induce apoptosis by inhibiting the PI3K/AKT pathway. Conclusion: Our findings identify that GIPC2 is associated with the PI3K/AKT signaling pathway and may represent a potential therapeutic target and biomarker for the management of AML.

Parental prepregnancy obesity and offspring overweight before two years of age among Chinese women with gestational diabetes.

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.

Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus.

BACKGROUND: Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM. METHODS: A nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM. RESULTS: The CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61-14.4) to 19.6 (5.65-68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07-5.28) to 12.1 (3.22-45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01-11.0) to 11.4 (3.98-32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant. CONCLUSIONS: The CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group.

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study.

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.

Adverse pregnancy outcomes are associated with an increased risk of postpartum prediabetes and diabetes in Chinese women with gestational diabetes.

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.

Branched-Chain Amino Acids and Their Interactions With Lipid Metabolites for Increased Risk of Gestational 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.

Eye disorders associated with newer antiepileptic drugs: A real-world disproportionality analysis of FDA adverse event reporting system.

BACKGROUND: Newer antiepileptic drugs such as levetiracetam, lacosamide, topiramate, gabapentin, oxcarbazepine, lamotrigine, and zonisamide are prescribed by physicians for the treatment of epilepsy. These drugs are also associated with a series of eye disorders. However, very few studies have systemically compared eye disorders associated with newer AEDs in a large sample of patients diagnosed with epilepsy. OBJECTIVE: This study aimed to evaluate the association between eye disorders and several newer AEDs, and also to examine the differences in the frequency of adverse events across individual AEDs through data mining of the self-reporting US Food and Drug Administration Adverse Event Report System (FAERS) database. METHODS: The definition relied upon system organ class and preferred terms according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was used to detect the risk signals from the FAERS database. The proportional reporting ratio, and χ2 (chi-square) values were calculated to assess the association between AEs and AED use. RESULTS: FAERS reports for 158,095 cases from January 1 of 2015 to September 30 of 2020 were included. AEDs were associated with a series of eye-related AEs that were defined by 106 preferred terms and could be classified into 10 aspects. CONCLUSION: There is variation in the types and severity of eye-related AEs across individual AEDs. Typically, topiramate and lamotrigine are more likely to cause serious eye-related AEs. In contrast, lacosamide rarely results in any severe eye-related AEs, and only diplopia and metamorphopsia are significant. levetiracetam tends to produce ocular neuromuscular disorder-related AEs. Macula-related AEs are associated with gabapentin. zonisamide appears to be closely associated with choroidal effusion and angle-closure glaucoma. oxcarbazepine is primarily associated with several cornea-related AEs.

Biofilm and pathogenic factor analysis of Gardnerella vaginalis associated with bacterial vaginosis in Northeast China.

Introduction: Gardnerella vaginalis is a major pathogen responsible for bacterial vaginosis (BV). However, the recurrence of infection and the antibiotic resistance of biofilms remain significant challenges for the treatment of BV. In this study, we aimed to analyze the pathogenic factors and drug sensitivity associated with the clinical treatment of BV in Northeast China. Methods: Subgroups were identified by clade-specific polymerase chain reaction (PCR). Biofilm formation was measured by crystal violet staining, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The inhibition and eradication of biofilm formation were measured by XTT and broth recovery-based methods. Results: Of the 24 samples of G. vaginalis, 11 samples and American Type Culture Collection (ATCC) 14018 formed biofilms; the remainder did not. The positive rates of detection for the sialidase A and vly genes in the 24 G. vaginalis samples were 100% and 79.2%, respectively. Moreover, 21 samples (87.5%) showed resistance to metronidazole and 16 (66.7%) presented with sensitivity towards clindamycin. The biofilm MIC80 (BMIC80) of metronidazole for ATCC14018 was 16 µg/ml while that of clindamycin was 0.125 µg/ml. The minimum biofilm eradication concentration (MBEC) of metronidazole was > 256 µg/ml while that of clindamycin was > 2 µg/ml. Discussion: Our results revealed that G. vaginalis is more resistant to metronidazole than clindamycin and neither metronidazole nor clindamycin are able to effectively eradicate vaginal biofilms. Thus, the role of antibiotics and biofilms in BV requires further investigation.

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta-analysis with more than half a million offspring.

We conducted a meta-analysis to evaluate the association of maternal gestational diabetes mellitus (GDM) and offspring overweight from birth to adulthood, and to assess the effects of lifestyle interventions in women with GDM on this risk of offspring overweight. We identified literature from PubMed and 12 other electronic databases and retrieved relevant literature published before October 20, 2020. Random-effects model analysis was used to calculate relative risks (RRs) of overweight and weighted mean differences of body mass index among children stratified into different developmental stages. Forty-nine cohort studies (n = 559,377) and four randomized controlled trials (n = 1277) were included. We found that offspring of women with GDM were at an increased risk for overweight with age, from 1.14 (95% confidence interval [CI]: 1.06-1.22) under 5 years, 1.37 (95% CI: 1.31-1.44) at 5 to <10 years, 2.00 (95% CI: 1.79-2.23) at 10 to <18 years, to 2.05 (95% CI: 1.65-2.55) over 18 years of age (p < 0.05 for differences among groups). However, it was not observed that lifestyle interventions for GDM decreased the elevated overweight risk (RR: 0.94, 95% CI: 0.80-1.11, I2 = 0.0%). These findings highlight the need for adopting an active and healthy lifestyle in this high-risk group.

Predictive values of serum metabolites in early pregnancy and their possible pathways for gestational diabetes: A nested case-control study in Tianjin, China.

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.

Prevalence of myopia in 3-14-year-old Chinese children: a school-based cross-sectional study in Chengdu.

BACKGROUND: The prevalence of myopia among children in Chengdu is unknown. The aim of this study was to determine the prevalence of myopia in 3- to 14-year-old Chinese children in Chengdu. METHODS: This study was a school-based cross-sectional study in children aged 3-14 years. Visual acuity (VA), spherical equivalent error (SER) with noncycloplegic autorefraction, axial length (AL) and corneal radius (CR) were measured. RESULTS: A total of 19,455 children were recruited for this study. The prevalence of myopia was 38.1 %; the prevalence of low myopia was 26.6 %, that of moderate myopia was 9.8 %, and that of high myopia was 1.7 %. The prevalence of myopia and SER increased with age from 6 years old. The prevalence of myopia was higher, and the SER indicated more severe myopia in the girls than in the boys (40.1 % vs. 36.2 %, χ2 = 30.67, df = 1, P < 0.001; -0.93 D ± 1.75 D vs. -0.84 D ± 1.74 D, t = 3.613, df=19,453, P < 0.001). The girls had a higher prevalence of myopia and myopic SER than did the boys aged 9 years and older (P < 0.05). Among the myopic children, the rates of uncorrected, undercorrected and fully corrected myopia were 54.8 %, 31.1 and 14.1 %, respectively. AL and AL/CR increased with age from 6 years old, but CR remained stable after 4 years old. The AL was longer, and the CR was flatter in the boys than in the girls aged 3 to 14 years old (P < 0.05). CONCLUSIONS: The prevalence of myopia, AL and AL/CR increased, and the SER became more myopic with age from 6 years old. The girls had a higher prevalence of myopia and myopic SER than did the boys, but the boys had a longer AL, flatter CR and higher AL/CR ratio than did the girls. The rate of uncorrected myopia was very high in the myopic children. More actions need to be taken to decrease the prevalence of myopia, especially uncorrected myopia in children.

Serum concentrations of SFAs and CDKAL1 single-nucleotide polymorphism rs7747752 are related to an increased risk of gestational diabetes mellitus.

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.

Physical activity and sleep duration during pregnancy have interactive effects on caesarean delivery: a population-based cohort study in Tianjin, China.

BACKGROUND: There were inconsistent findings in the literature regarding the associations of physical activity and sleep duration during pregnancy with caesarean delivery for different reasons. It was also unknown whether physical activity and sleep duration during pregnancy had interactive effects on the risks of different types of caesarean delivery. The study aimed to investigate the effects of physical activity, sleep duration and their interactions on the risk of caesarean delivery for medical reasons and non-medical reasons. METHODS: From October 2010 to August 2012, a prospective population-based cohort of 13,015 pregnant women was established in six central urban districts of Tianjin, China. Pregnancy outcomes were retrieved from an electronic database and caesarean delivery was divided into caesarean delivery for medical reasons and caesarean delivery for non-medical reasons. Physical activity and sleep status were collected at 24-28 weeks of gestation using self-reported questionnaires. Logistic regression and additive interaction were used to examine physical activity, sleep duration and their interactive effects on risk of caesarean delivery. RESULTS: In the cohort, 5692 (43.7%) and 2641 (20.3%) of women had caesarean delivery for medical reasons and non-medical reasons, respectively. Low physical activity increased the risk of caesarean delivery for medical reasons (adjusted OR: 1.13, 95%CI 1.04-1.23) but not caesarean delivery for non-medical reasons. Sleep duration < 7 h/day and poor sleep quality were not associated with caesarean delivery. Sleep duration ≥9 h/day increased the risk of caesarean delivery for medical reasons (1.12, 1.02-1.22) and caesarean delivery for non-medical reasons (1.16, 1.05-1.29). Co-presence of low physical activity and sleep duration ≥9 h/day increased risk of caesarean delivery (1.25, 1.12-1.41), and their additive interaction was statistically significant for caesarean delivery for medical reasons but not for caesarean delivery for non-medical reasons. CONCLUSIONS: Low physical activity and excessive sleep duration during pregnancy each increased the risk of caesarean delivery, and they had an interactive effect on the risk of caesarean delivery for medical reasons but not on the risk of caesarean delivery for non-medical reasons. Increasing physical activity and maintaining recommended sleep duration during pregnancy may have benefits for perinatal health.

The Therapeutic Relationship in China: A Systematic Review and Meta-Analysis.

With a surge of conflicts between healthcare workers and patients in recent years, the therapeutic relationship (TR) in China is presently in tension. Meanwhile, consequent issues have begun to emerge, such as the distrust between healthcare workers and patients and the decline in the quality of medical services. Although many empirical studies about the TR have been conducted in China, previous studies on TR and its influencing factors have been contradictory. Therefore, this study conducted a systematic review and meta-analysis to assess the current situation of the TR and to identify factors associated with the TR in Chinese hospitals from three perspectives (healthcare worker, patient, and therapeutic interaction). Two reviewers independently searched the literature, selected researches, and extracted data through comprehensively searching of three international electronic databases and three Chinese electronic databases to identify all relevant observational studies on influencing factors for TR in China published in English and Chinese from January 2000 to January 2020. Among the 3290 records initially identified, 11 studies met the selection criteria. A total of 96,906 individuals were included in the review. The results showed that 55.73% of healthcare workers consider the TR to be tense, and 33.7% of patients hold this view. The meta-analysis indicated that healthcare workers who were male, older, less educated, working in a non-surgical department, and had a senior title were more likely to be pessimistic about the TR. Patients who were rural residents, highly educated, and had no medical insurance were more likely to be pessimistic about the TR. Furthermore, the mutual trust could improve rapport between healthcare workers and patients. The 25 other related factors related to the TR were analyzed and described using a narrative approach. The findings might deserve consideration in the design of relative policies to promote harmony between doctors and patients.

Usefulness of cut-off points of International criteria for prediction of post-partum diabetes and prediabetes among Chinese women with gestational diabetes.

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.

Machine learning risk score for prediction of gestational diabetes in early pregnancy in Tianjin, China.

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_risk_calculator/). CONCLUSION: The XGBoost model achieved better performance than the logistic model.

Ceramides and their interactive effects with trimethylamine-N-oxide metabolites on risk of gestational diabetes: A nested case-control study.

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.