Maternal Glucose Research Articles

Risk of Neonatal Hypoglycemia in Infants of Mothers With Gestational Glucose Intolerance.

To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia. This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%. Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis. GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health.

Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study

BackgroundLimited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT).MethodsA population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values.ResultsOut of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04–0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64–13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L).ConclusionsFor newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective prebirth cohort (n=2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n=27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Sheng Zhen Gong in pregnancy: The effects of a traditional low intensity exercise form on maternofetal health and wellbeing

Objective: The aim of the study was to evaluate maternal and fetal responses to Sheng Zhen Gong (SZG), a low intensity form of exercise, using multi-modal antenatal surveillance techniques. Methods: This was a single-blinded randomized controlled trial in low risk pregnant women from a tertiary center in the Philippines. Participants were randomized into Chronic Exercise (CE), Acute Exercise (AE) and No Exercise (NE) groups. A Pregnancy Physical Activity Questionnaire (PPAQ) was given to ascertain baseline activities. Systematic periodic assessment was performed utilizing standard ultrasound and Doppler studies between 20+0 to 32+0 weeks gestation with or without sessions involving a biophysical and Warwick-Edinburgh Mental Well-being Scale (WEMWBS) evaluation before and after SZG exercise. Results: Eighty-nine (89) women were included with average energy expenditures of light to moderate intensity. In the CE group, systolic, diastolic, mean arterial pressures and heart rates were lower while oxygen saturations increased after exercise (n=35; p: &lt;0.01 to 0.01). There were also observable significant increases in maternal well-being scores after exercise for both CE (n=35) and AE (n=21) groups (p&lt;0.01). Increasing the frequency of exercise was also associated with better maternal well-being (p: 0.02). Fetal Doppler studies showed no significant changes after exercise. Conclusion: In normal pregnancy, routine low intensity physical activity in the form of SZG was seen to have positive effects on maternal cardiovascular, blood glucose and mental well-being maintenance with no evidence of detrimental effects on the fetus.

Gestational and Postpartum Exposure to PM2.5 Components and Glucose Metabolism in Chinese Women: A Prospective Cohort Study.

Pregnant women are physiologically prone to glucose intolerance, while the puerperium represents a critical phase for recovery. However, how air pollution disrupts glucose homeostasis during the gestational and early postpartum periods remains unclear. This prospective cohort study conducted an oral glucose tolerance test and measured the insulin levels of 834 pregnant women in Guangzhou, with a follow-up for 443 puerperae at 6-8 weeks postpartum. Residential PM2.5 and five chemical components were estimated by an established spatiotemporal model. The adjusted linear model showed that an IQR increase in gestational PM2.5 exposure was associated with an increase of 0.17 mmol/L (95% CI: 0.06, 0.28) in fasting plasma glucose (FPG) and 0.24 (95% CI: 0.05, 0.42) in the insulin resistance index. Postpartum PM2.5 exposure was linked to a 0.17 mmol/L (95% CI: 0.05, 0.28) elevation in FPG per IQR, with a strengthened association found in women with gestational diabetes (Pinteraction = 0.003). In the quantile-based g-computation model, NO3- consistently contributed to the combined effect of PM2.5 components on gestational and postpartum FPG. This study was the first to suggest that PM2.5 components were associated with exacerbated gestational insulin resistance and elevated postpartum FPG. Targeted interventions reducing the emissions of toxic PM2.5 components are essential to improving maternal glucose metabolism.

Glucose at gestational diabetes diagnosis predicts neonatal hypoglycaemia, large-for-gestational age and post-partum abnormal maternal glucose homeostasis

Glucose at gestational diabetes diagnosis predicts neonatal hypoglycaemia, large-for-gestational age and post-partum abnormal maternal glucose homeostasis

Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM)

BackgroundGestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy.AimsThe study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women’s neonates and fetuses born to mothers with GDM.Materials and methodsCord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit.ResultsFetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age.ConclusionThese findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

Ultrasonographic diagnosis of fetal hemodynamic parameters in pregnant women with diabetes mellitus in the third trimester of pregnancy

ObjectiveIt was to investigate the diagnosis of fetal hemodynamics in pregnant women with diabetes mellitus in the third trimester of pregnancy by color Doppler ultrasonography. Methods55 women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy who were clinically diagnosed and treated in Haian City People's Hospital of Jiangsu Province were selected as the observation group, and 55 pregnant women with normal prenatal examination results were selected as the controls. The hemodynamic parameters of fetal middle cerebral artery (MCA), umbilical artery (UA), and renal artery (RA) were detected, including the ratio of maximum systolic blood flow velocity to end-diastolic blood flow velocity (S/D), resistance index (RI) and arterial pulsation index (PI). Fasting serum levels of maternal patients were collected for detecting Cystain C (Cys C) and homocysteine (Hcy) to analyze the predictive value of serological indexes and target arterial hemodynamics parameters for adverse pregnancy outcome (APO). ResultsThe results showed that compared with controls, in the observation group, RI, PI, and S/D of MCA and RA increased significantly, while RI, PI and S/D of UA decreased obviously (P < 0.05), the levels of serum Cys C and Hcy were clearly increased (P < 0.05). The APO rate of controls and observation group was 10.91 % and 25.45 %, respectively. It was found that the area under the curve of serum Cys C, Hcy, and the APO predicted by the hemodynamic parameters of fetal MCA, UA, and RA were all greater than 0.75 (P < 0.05). Multiple Logistic regression analysis showed that serum Cys C and Hcy, and the hemodynamic parameters of fetal MCA, UA and RA were correlated with APO (P < 0.05). ConclusionIn summary, maternal blood glucose level can affect fetal hemodynamic parameters. In the third trimester of pregnancy, the changes of blood flow parameters of fetal MCA, UA, RA, and maternal serum Cys C and Hcy levels are helpful to understand fetal status in utero, and can be used to predict APO.

Association Between Maternal Fasting Glucose Levels Throughout Pregnancy and Preschoolers' Refractive Errors.

We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years of age. Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study. Using the group-based trajectory model, trajectory fitting was performed on FPG levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity. Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error (odds ratio [OR] = 1.46 [95% CI: 1.08, 1.97]), hypermetropia (OR = 1.64 [95% CI: 1.09, 2.46]), and astigmatism (OR = 1.60 [95% CI: 1.06, 2.41]) at age 6 compared to those with low level trajectory. Maternal blood glucose level in the first (β = -.012 [95% CI: -.024, -.001]) and the second (β = -.016 [95% CI: -.025, -.006]) trimesters was associated with 6-year-old children's distance vision value. High level of FPG trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia, and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study.

Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study

BackgroundMaternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls.MethodsIn this prospective, longitudinal case-control study — including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women — fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors — including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) — were analyzed across three time periods: the last menstrual period to 13 (V1), 14–22 (V2), and 23–32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed.ResultsAt 28–32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18–22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28–32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester.ConclusionIn women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

Automated closed-loop insulin delivery for the management of type 1 diabetes during pregnancy: the AiDAPT RCT

Background There are over 2000 pregnancies annually in women with type 1 diabetes in the UK. Despite recent improvements in diabetes technology, most women cannot achieve and maintain the recommended pregnancy glucose targets. Thus, one in two babies experience complications requiring neonatal care unit admission. Recent studies demonstrate that hybrid closed-loop therapy, in which algorithms adjust insulin delivery according to continuous glucose measurements, is effective for managing type 1 diabetes outside of pregnancy, but efficacy during pregnancy is unclear. Objective To examine the clinical efficacy of hybrid closed-loop compared to standard insulin therapy in pregnant women with type 1 diabetes. Design A multicentre, parallel-group, open-label, randomised, controlled trial in pregnant women with type 1 diabetes. Setting Nine antenatal diabetes clinics in England, Scotland and Northern Ireland. Participants Pregnant women with type 1 diabetes and above-target glucose levels, defined as glycated haemoglobin A1c of ≥ 48 mmol/mol (6.5%) in early pregnancy. Interventions A hybrid closed-loop system compared to standard insulin delivery (via insulin pump or multiple daily injections) with continuous glucose monitoring. Outcome measures The primary outcome is the difference between the intervention and control groups in percentage time spent in the pregnancy glucose target range (3.5–7.8 mmol/l) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Secondary outcomes include overnight time in range, time above range (&gt; 7.8 mmol/l), glycated haemoglobin A1c, safety outcomes (diabetic ketoacidosis, severe hypoglycaemia, adverse device events), psychosocial functioning obstetric and neonatal outcomes. Results The percentage of time that maternal glucose levels were within target range was higher with closed-loop than standard insulin therapy: 68.2 ± 10.5 in closed-loop and 55.6 ± 12.5 in the control group (mean‑adjusted difference 10.5 percentage points, 95% confidence interval 7.0 to 14.0; p &lt; 0.001). Results were consistent in secondary outcomes, with less time above range (−10.2%, 95% confidence interval −13.8 to −6.6%; p &lt; 0.001), higher overnight time in range (12.3%, 95% confidence interval 8.3 to 16.2%; p &lt; 0.001) and lower glycated haemoglobin A1c (−0.31%, 95% confidence interval −0.50 to −0.12%; p &lt; 0.002) all favouring closed-loop. The treatment effect was apparent from early pregnancy and consistent across clinical sites, maternal glycated haemoglobin A1c categories and previous insulin regimen. Maternal glucose improvements were achieved with 3.7 kg less gestational weight gain and without additional hypoglycaemia or total daily insulin dose. There were no unanticipated safety problems (six vs. five severe hypoglycaemia cases, one diabetic ketoacidosis per group) and seven device-related adverse events associated with closed-loop. There were no between-group differences in patient-reported outcomes. There was one shoulder dystocia in the closed-loop group and four serious birth injuries, including one neonatal death in the standard care group. Limitations Our results cannot be extrapolated to closed-loop systems with higher glucose targets, and our sample size did not provide definitive data on maternal and neonatal outcomes. Conclusions Hybrid closed-loop therapy significantly improved maternal glycaemia during type 1 diabetes pregnancy. Our results support National Institute for Health and Care Excellence guideline recommendations that hybrid closed-loop therapy should be offered to all pregnant women with type 1 diabetes. Future work Future trials should examine the effectiveness of hybrid closed-loop started before pregnancy, or as soon as possible after pregnancy confirmation. Trial registration This trial is registered as ISRCTN56898625. Funding This award was funded by the National Institute of Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 16/35/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 7. See the NIHR Funding and Awards website for further award information. Dexcom supplied the continuous glucose monitoring systems used by AiDAPT intervention- and control-arm participants at reduced cost.

Clinical Effectiveness of Continuous Glucose Monitoring in Pregnancies Affected by Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves neonatal outcomes in type 1 diabetes pregnancies; however, its effectiveness has not been assessed in a real-world setting in the United States. Objective: The Triple C Study aimed to examine the clinical effectiveness, assessed through maternal glucose control and gestational health outcomes, of CGM use compared with self-monitoring of blood glucose (SMBG) in pregnancies associated with type 1 diabetes in a real-world setting. Research Design and Methods: We retrospectively identified 160 type 1 diabetes pregnancies at the Barbara Davis Center for Diabetes managed with CGM therapy (n = 109) or SMBG (n = 51) over a 6.5-year period (2014-2020). Obstetric care was provided at multiple practices. CGM use was defined as ≥60% wear in the second and third trimesters of pregnancy. Data were obtained from the electronic medical record system, hospital records, and vital statistics departments (Colorado and Wyoming). We used Student's t-test for continuous variables and chi-square test for categorical variables to compare outcomes between groups. Results: The CGM group had more participants meeting trimester-specific hemoglobin A1C (HbA1c) goals throughout pregnancy and postpartum (P < 0.01 in each time period). The CGM group had fewer participants never meeting HbA1c goals in any trimester than the SMBG group (P < 0.001). There were no significant differences in neonatal outcomes between groups, other than for macrosomia (12.8% CGM vs. 29.4% SMBG, P = 0.01). Infants of CGM users required a neonatal intensive care unit admission less often (52.9% CGM vs. 68.3% SMBG, P = 0.0989). Conclusions: CGM use was associated with improved maternal glucose levels in a diverse real-world cohort.

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations

Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity.Graphical

Triglyceride-glucose index in early pregnancy predicts the risk of gestational diabetes: a prospective cohort study

ObjectiveThis study aimed to investigate the association between the triglyceride-glucose (TyG) index in early pregnancy and the development of gestational diabetes mellitus (GDM) in the second trimester. The primary objectives were to evaluate the predictive potential of the TyG index for GDM, determine the optimal threshold value of the TyG index for GDM assessment, and compare the predictive performance of the TyG index alone versus its combination with maternal age and pre-pregnancy body mass index on GDM. Moreover, the study explored the association between the TyG index in early pregnancy and the risk of other pregnancy-related complications (PRCs), such as placental abruption and gestational hypertension.Patients and methodsThis prospective cohort study recruited 1,624 pregnant women who underwent early pregnancy antenatal counseling and comprehensive assessments with continuous monitoring until delivery. To calculate the TyG index, health indicators, including maternal triglycerides and fasting plasma glucose, were measured in early pregnancy (< 14 weeks of gestation). The predictive power of the TyG index for evaluating GDM in Chinese pregnant women was determined using multifactorial logistic regression to derive the odds ratios and 95% confidence interval (CI). Subgroup analyses were conducted, and the efficacy of the TyG index in predicting PRCs was assessed via receiver operating characteristic (ROC) curve analysis and restricted cubic spline, with the optimal cutoff value calculated.ResultsLogistic regression analyses revealed a 2.10-fold increase in the GDM risk for every 1-unit increase in the TyG index, after adjusting for covariates. The highest GDM risk was observed in the group with the highest TyG index compared with the lowest quintile group (odds ratios: 3.25; 95% CI: 2.23–4.75). Subgroup analyses indicated that exceeding the recommended range of gestational weight gain and an increased GDM risk were significantly associated (P = 0.001). Regarding predictive performance, the TyG index exhibited the highest area under the curve (AUC) value in the ROC curve for GDM (AUC: 0.641, 95% CI: 0.61–0.671). The optimal cutoff value was 8.890, with both sensitivity and specificity of 0.617.The combination of the TyG index, maternal age, and pre-pregnancy body mass index proved to be a superior predictor of GDM than the TyG index alone (AUC: 0.672 vs. 0.641, P < 0.01). After adjusting for multiple factors, the analyses indicated that the TyG index was associated with an increased risk of gestational hypertension. However, no significant association was noted between the TyG index and the risk of preeclampsia, placental abruption, intrauterine distress, or premature rupture of membranes.ConclusionThe TyG index can effectively identify the occurrence of GDM in the second trimester, aligning with previous research. Incorporating the TyG index into routine clinical assessments of maternal health holds significant practical implications. Early identification of high-risk groups enables healthcare providers to implement timely interventions, such as increased monitoring frequency for high-risk pregnant women and personalized nutritional counseling and health education. These measures can help prevent or alleviate potential maternal and infant complications, thereby enhancing the overall health outcomes for both mothers and babies.

Gestational diabetes mellitus, hypertension, and dyslipidemia as the risk factors of preeclampsia

Gestational diabetes mellitus (GDM) is a known risk factor for gestational hypertension which further progress toward conditions like proteinuria, dyslipidemia, thrombocytopenia, pulmonary edema leading to Preeclampsia (PE). Pregnancy can be a challenging time for many women, especially those diagnosed with GDM and PE. Thus, the current prospective study investigates the association of OGTT glucose levels with systolic and diastolic blood pressure and lipid profile parameters in pregnant women diagnosed with GDM and PE. A total of 140 pregnant women were stratified into GDM (n = 50), PE (n = 40) and controls (n = 50). Two hour 75 g oral glucose tolerance test (OGTT) was performed for screening GDM. Biochemical parameters analysis of OGTT, total cholesterol (TC), triglyceride (Tg), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), urinary albumin and creatinine were tested to find urinary albumin creatinine ratio (uACR). Statistical analysis was performed using ANOVA followed by post hoc test and regression analysis. Among the studied groups, GDM and PE groups showed no significant difference in age and increased BMI. Increased 2 h OGTT & TC in GDM group; elevated uACR, systolic/diastolic blood pressure, Tg, HDL-C, LDL-C in PE group was observed and differ significantly (p < 0.0001) with other groups. A significant positive effect of 2 h OGTT was observed on blood pressure (R2: GDM = 0.85, PE = 0.71) and lipid profile determinants (R2: GDM = 0.85, PE = 0.33) at p < 0.0001. The current study concludes that glucose intolerance during the later weeks of pregnancy is associated with gestational hypertension and hyperlipidemia as a risk factor for PE. Further research is needed for a detailed assessment of maternal glucose metabolism at various pregnancy stages, including the use of more sensitive markers such as C-peptide and their relation to pregnancy-related hypertensive disorders.

Triglyceride-glucose index: A promising biomarker for predicting risks of adverse pregnancy outcomes in Hangzhou, China

IntroductionThe triglyceride-glucose (TyG) index has been recommended as an alternative indicator of insulin resistance (IR). However, the association between the TyG index and adverse pregnancy outcomes remains to be elucidated. MethodsThe present retrospective study was conducted at Women's Hospital, Zhejiang University School of Medicine and involved a total of 8,514 participants. Maternal fasting lipid profiles and glucose concentrations were measured. Based on the TyG index, the participants were categorized into quartiles. Logistic regression analysis was used to calculate odds ratios (ORs) for each quartile with reference to the first quartile, while receiver operating characteristic (ROC) curve analysis, Hosmer–Lemeshow test, and calibration curve analysis were employed to evaluate the predictive ability of the TyG index for adverse pregnancy outcomes. ResultsThe TyG index was higher in patients with preeclampsia, preterm birth, and macrosomia. On univariate analysis, there was an increased risk of developing adverse pregnancy outcomes with increasing quartiles of the TyG. After adjusting for potential confounders in multivariable logistic regression analysis, a positive independent correlation was found between the TyG index and preeclampsia, preterm birth, and macrosomia. In ROC curve analysis for predicting the risks of preeclampsia, preterm birth, and macrosomia, the area under the curve (AUC) could reach 0.665, 0.588, and 0.606, respectively. These predictive models demonstrated good calibration (all P > 0.05). ConclusionsThe TyG index showed a good predictive capacity for assessing the risk of adverse pregnancy outcomes, and it should receive sufficient clinical attention.

A maternal low-protein diet impaired glucose metabolism and altered the lncRNA profiles of islets in adult offspring

A maternal low-protein diet during pregnancy can increase children's susceptibility to diabetes mellitus in adulthood. However, whether long noncoding RNAs (lncRNAs) in islets participate in the development of diabetes in adult offspring following maternal protein restriction is not fully understood. Female mice were fed a low-protein (LP) diet or control diet throughout gestation and lactation. The male offspring were then randomly divided into two groups according to maternal diet: offspring from control diet group dams (Ctrl group) and offspring from LP group dams (LP group). We observed the glucose metabolism of adult offspring. A lncRNA microarray was constructed for the islets from the LP group and Ctrl group to explore the differently expressed lncRNAs. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were subsequently used to predict the functions of the differently expressed lncRNAs. The body weight from birth to 12 weeks of age was significantly lower in the LP offspring. Adult LP offspring exhibited impaired glucose tolerance and decreased insulin secretion, consistent with the reduction in β-cell proliferation. According to the lncRNA microarray, four lncRNAs, three upregulated lncRNAs, and one downregulated lncRNA were differently expressed in LP offspring islets compared with Ctrl offspring. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed lncRNAs were mostly associated with the hypoxia-inducible factor-1α signaling pathway. Additionally, we validated the expression of these four differentially expressed lncRNAs via quantitative real-time polymerase chain reaction. Our findings demonstrated the expression patterns of lncRNAs in islets from adult offspring of mothers who consumed a maternal low-protein diet.

Post-load glucose is a stronger predictor of adverse pregnancy outcomes than first-trimester HbA1c in women without gestational diabetes.

A debate exists on the relation of adverse pregnancy outcomes with glycemic levels in early pregnancy. We aimed to investigate the association of maternal characteristics including post-load glucose and first-trimester HbA1c test results with adverse pregnancy outcomes in women without gestational diabetes mellitus. A dataset (January 2011 and September 2017) from a hospital prenatal clinic was explored to find the important predictors of adverse pregnancy outcomes using maternal characteristics and glucose assessments in mothers without gestational diabetes. We used two machine learning algorithms to capture nonlinearity in selecting important maternal characteristics and developed predictive models for each outcome. In total, 1,618 pregnant women were included in the analytic dataset with a mean (SD) age of 26.8 (3.5) years and gravida of 1.7 (0.9). Important associations were detected between maternal features and primary cesarean section, fetal distress, premature rupture of membranes, macrosomia, small or large for gestational age, APGAR <7 at 1 or 5 min, hyperbilirubinemia, and poly- or oligo-hydramnios. Overall, the predictive models showed good performance and large areas under the curves (0.732, 0.765, 0.646, 0.651, 0.730, 0.646, 0.684, 0.716, and 0.678, respectively). Specifically, they had high positive likelihood ratios. High glucose levels were associated with adverse pregnancy outcomes. Post-load glucose was the most reliable test for predicting the outcomes. Overall, fasting blood sugar was of more predictive value than HbA1c. Our study showed that further research should account for the nonlinearity and interactions inherent in the data.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Increasing maternal glucose concentrations is insufficient to restore placental glucose transfer in chorionic somatomammotropin RNA interference pregnancies.

We previously demonstrated impaired placental nutrient transfer in chorionic somatomammotropin (CSH) RNA interference (RNAi) pregnancies, with glucose transfer being the most impacted. Thus, we hypothesized that despite experimentally elevating maternal glucose, diminished umbilical glucose uptake would persist in CSH RNAi pregnancies, demonstrating the necessity of CSH for adequate placental glucose transfer. Trophectoderm of sheep blastocysts (9 days of gestational age; dGA) were infected with a lentivirus expressing either nontargeting control (CON RNAi; n = 5) or CSH-specific shRNA (CSH RNAi; n = 7) before transfer into recipient sheep. At 126 dGA, pregnancies were fitted with vascular catheters and underwent steady-state metabolic studies (3H2O transplacental diffusion) at 137 ± 0 dGA, before and during a maternal hyperglycemic clamp. Umbilical glucose and oxygen uptakes, as well as insulin and IGF1 concentrations, were impaired (P ≤ 0.01) in CSH RNAi fetuses and were not rescued by elevated maternal glucose. This is partially due to impaired uterine and umbilical blood flow (P ≤ 0.01). However, uteroplacental oxygen utilization was greater (P ≤ 0.05) during the maternal hyperglycemic clamp, consistent with greater placental oxidation of substrates. The relationship between umbilical glucose uptake and the maternal-fetal glucose gradient was analyzed, and while the slope (CON RNAi, Y = 29.54X +74.15; CSH RNAi, Y = 19.05X + 52.40) was not different, the y-intercepts and elevation were (P = 0.003), indicating reduced maximal glucose transport during maternal hyperglycemia. Together, these data suggested that CSH plays a key role in modulating placental metabolism that ultimately promotes maximal placental glucose transfer.NEW & NOTEWORTHY The current study demonstrated a novel, critical autocrine role for chorionic somatomammotropin in augmenting placental glucose transfer and maintaining placental oxidative metabolism. In pregnancies with CSH deficiency, excess glucose in maternal circulation is insufficient to overcome fetal hypoglycemia due to impaired placental glucose transfer and elevated placental metabolic demands. This suggests that perturbations in glucose transfer in CSH RNAi pregnancies are due to compromised metabolic efficiency along with reduced placental mass.