Continuous glucose monitoring in pregnancies with type 1 diabetes: small increases in time-in-range improve maternal and perinatal outcomes.

BACKGROUND: Continuous glucose monitors provide detailed information regarding glycemic control in pregnant patients with type 1 diabetes. Little data have been published examining the association between continuous glucose monitor parameters and perinatal outcomes among gravidas with type 1 diabetes using continuous glucose monitors. OBJECTIVE: This study aimed to examine the association between perinatal outcomes and time-in-range as assessed by continuous glucose monitors used in pregnant individuals with type 1 diabetes. We hypothesized that higher time-in-range would be associated with lower risk of adverse perinatal outcomes. STUDY DESIGN: This multicenter retrospective cohort study included all gravidas with type 1 diabetes using continuous glucose monitors who delivered from 2020 to 2022 at 5 University of California sites. Only those with continuous glucose monitor target range set to 70 to 140 mg/dL (±10 mg/dL) were included. Time-in-range (%) was recorded at 12, 16, 20, 24, 28, and 32 weeks. The primary maternal and neonatal outcomes were preeclampsia and large for gestational age, defined as birthweight ≥95th percentile. Kruskal-Wallis tests were used to compare median time-in-range between those with and without the primary outcomes. Log-binomial regression was used to obtain risk ratios, with adjustment for microvascular disease and years with type 1 diabetes. RESULTS: A total of 91 patients were included. Most used an insulin pump (81%) and did not have diabetic microvascular disease (72%). Median time since diagnosis of type 1 diabetes was 16 years, and median periconception hemoglobin A1c was 6.7%. Compared with those with preeclampsia, normotensive gravidas had significantly higher time-in-range at nearly every time point. A similar pattern was observed for those with normal-birthweight infants compared with large-for-gestational-age infants. On adjusted analyses, every 5-unit increase in time-in-range at 12 weeks was associated with 45% and 46% reductions in the risks of preeclampsia and large for gestational age, respectively (preeclampsia: adjusted risk ratio, 0.55; 95% confidence interval, 0.30-0.99; large for gestational age: adjusted risk ratio, 0.54; 95% confidence interval, 0.29-0.99). CONCLUSION: Higher time-in-range is associated with lower risk of preeclampsia and large for gestational age. This association is observed early in gestation, when each 5-unit increase in time-in-range is associated with ∼50% reduction in the risk of these complications. These findings can be used to counsel patients regarding the risk of pregnancy complications at specific time-in-range values, and to encourage patients that even small improvements in time-in-range can have significant impact on pregnancy outcomes. Larger studies are needed to further explore these findings and to identify optimal time-in-range to reduce perinatal complication rates.

Changes in the shape and function of the fetal heart of pre- and gestational diabetes mothers.

BACKGROUND: Hyperglycemia during pregnancy can affect fetal heart in many ways, including causing cardiac malformation, leading to hypertrophic cardiomyopathy and cardiac dysfunction. Echocardiographic evaluation can assist identify alterations in heart structure, morphology and function, enabling prompt monitoring and management. However, according to earlier research, the cardiac alterations are modest in hyperglycemic mothers' fetuses, and might not be detectable using conventional methods and it is also unclear whether these changes are related to the metabolism of mothers. Fetal Heart Quantification (Fetal HQ) can assess ventricular geometry and function more sensitively and thoroughly, and identify sub-clinical cardiac dysfunction. The purpose of this study was to evaluate fetal heart by Fetal HQ in fetuses of hyperglycemic mothers who either had pre-gestational or gestational diabetes and to correlate them with maternal metabolic indices. METHODS: The fetuses of 25 gestational age-matched control mothers, 48 women with gestational diabetes mellitus (GDM), and 11 women with diabetes mellitus (DM) were included in the prospective case-control research. Using fetal echocardiography and speckle tracking echocardiography (STE), the heart of the fetus was evaluated. Differences in the groups' anthropometric, metabolic, and cardiac parameters were examined. It was assessed whether maternal features, prenatal glucose, lipids, and maternal hemoglobin A1c (HbA1c) correlated with fetal cardiac parameters. RESULTS: The LV EDV and ESV were significantly higher in the GDM group as compared to the DM group (p < 0.05). The GSI% was significantly lower in the GDM group compared with the control (p < 0.05). The LV SV and CO of the GDM group were both significantly higher compared with the DM group (p < 0.05). There was a significant decrease in RV FS for segments 1-7 in GDM fetuses compared to the control (p < 0.05) and for segments 5-10 compared to DM (p < 0.05). Fetal cardiac morphology and function indices correlate with maternal pregestational weight, BMI, early pregnancy fast glucose, lipids, and glycemic control levels. CONCLUSIONS: Fetuses exposed to gestational diabetes have altered heart morphology and function that is linked to maternal metabolic parameters, which presents a special indication for performing geometry and function cardiac assessment. Fetal HQ can be employed to evaluate the fetal cardiac shape and function in fetuses exposed to gestational diabetes.

Elevated galectin-3 levels detected in women with hyperglycemia during early and mid-pregnancy antagonizes high glucose - induced trophoblast cells apoptosis via galectin-3/foxc1 pathway.

OBJECTIVE: This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure. METHODS: The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry. RESULTS: Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose - induced apoptosis. CONCLUSION: Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy.

Impact of experiencing multiple vulnerabilities on fetal growth and complications in women with hyperglycemia in pregnancy.

BACKGROUND: In women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators-food insecurity and poor language proficiency-on adherence to prenatal care and maternal and fetal outcomes. METHODS: In a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes. RESULTS: Among the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency. CONCLUSION: We found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers.

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Hyperglycemia in Pregnancy-Associated Oxidative Stress Augments Altered Placental Glucose Transporter 1 Trafficking via AMPKα/p38MAPK Signaling Cascade.

GLUT1, being a ubiquitous transporter isoform, is considered primarily responsible for glucose uptake during glycolysis. However, there is still uncertainty about the regulatory mechanisms of GLUT1 in hyperglycemia in pregnancy (HIP, PGDM, and GDM) accompanied by abnormal oxidative stress responses. In the present study, it was observed that the glycolysis was enhanced in GDM and PGDM pregnancies. In line with this, the antioxidant system was disturbed and GLUT1 expression was increased due to diabetes impairment in both placental tissues and in vitro BeWo cells. GLUT1 responded to high glucose stimulation through p38MAPK in an AMPKα-dependent manner. Both the medical-mediated and genetic depletion of p38MAPK in BeWo cells could suppress GLUT1 expression and OS-induced proapoptotic effects. Furthermore, blocking AMPKα with an inhibitor or siRNA strategy promoted p38MAPK, GLUT1, and proapoptotic molecules expression and vice versa. In general, a new GLUT1 regulation pathway was identified, which could exert effects on placental transport function through the AMPKα-p38MAPK pathway. AMPKα may be a therapeutic target in HIP for alleviating diabetes insults.

Non-fasting OGTT versus Fasting OGTT for screening of Hyperglycaemia in Pregnancy (HIP).

OBJECTIVES: To compare the reliability of non-fasting oral glucose tolerance test (OGTT) versus fasting OGTT for screening of hyperglycaemia in pregnancy (HIP). METHODS: This cross sectional analytic study was conducted by the Department of Obstetrics & Gynaecology, Isra University Karachi Campus from October 2016 to April 2017. A total of 225 pregnant women irrespective of gestational age were included in the study. They underwent non fasting 75 grams OGTT. Venous plasma glucose was done 02 hours after the glucose load. Same women were advised to come again within three to seven days for fasting OGTT. Venous plasma glucose (VPG) was estimated in fasting and 2 hours post glucose load. RESULTS: Using the non-fasting OGTT, out of 204 women, 32 were diagnosed with hyperglycemia. All these 204 women were again called for fasting OGTT three to seven days after the initial non-fasting OGTT. Only nine were diagnosed with hyperglycemia, out of these nine women, seven women who were screen positive on non-fasting OGTT were found to be screen positive on fasting OGTT as well. However, only two women were additionally diagnosed with hyperglycemia who were initially screen negative on non-fasting OGTT. The non-fasting OGTT has diagnosed HIP with sensitivity of 77.7%, specificity of 87.1%, positive predictive value of 21.8% and negative predictive value of 98.8%. CONCLUSION: The use of the non-fasting OGTT at first antenatal visit may be a practical approach to detect the HIP as screening and diagnostic tool in the resource constrained settings.

Mechanisms of Congenital Malformations in Pregnancies with Pre-existing Diabetes.

PURPOSE OF REVIEW: Fetuses of diabetic mothers are at increased risk for congenital malformations. Research in recent decades using animal and embryonic stem cell models has revealed many embryonic developmental processes that are disturbed by maternal diabetes. The aim of this review is to give clinicians a better understanding of the reasons for rigorous glycemic control in early pregnancy, and to provide background to guide future research. RECENT FINDINGS: Mouse models of diabetic pregnancy have revealed mechanisms for altered expression of tissue-specific genes that lead to malformations that are more common in diabetic pregnancies, such as neural tube defects (NTDs) and congenital heart defects (CHDs), and how altered gene expression causes apoptosis that leads to malformations. Embryos express the glucose transporter, GLUT2, which confers susceptibility to malformation, due to high rates of glucose uptake during maternal hyperglycemia and subsequent oxidative stress; however, the teleological function of GLUT2 for mammalian embryos may be to transport the amino sugar glucosamine (GlcN) from maternal circulation to be used as substrate for glycosylation reactions and to promote embryo cell growth. Malformations in diabetic pregnancy may be not only due to excess glucose uptake but also due to insufficient GlcN uptake. Avoiding maternal hyperglycemia during early pregnancy should prevent excess glucose uptake via GLUT2 into embryo cells, and also permit sufficient GLUT2-mediated GlcN uptake.

Evidence in support of the International Association of Diabetes in Pregnancy study groups' criteria for diagnosing gestational diabetes mellitus worldwide in 2019.

Gestational diabetes mellitus, the most frequent medical complication of pregnancy, affects 5-6% of women in the United States with the use of the currently predominant Carpenter-Coustan criteria, which still represent the preferred approach of the American College of Obstetricians and Gynecologists. Alternative criteria proposed by the International Association of Diabetes in Pregnancy Study Groups would likely increase gestational diabetes mellitus prevalence to 15-20%, because of both a 1-step testing policy and the requirement for only 1 elevated glucose value for diagnosis. Increasing gestational diabetes mellitus prevalence relates to older maternal age and the increasing prevalence of overweight and obesity. This increased gestational diabetes mellitus prevalence is consistent with 29.3% prevalence of prediabetes and 4.5% prevalence of known diabetes outside pregnancy in US adults from 20-44 years of age. Gestational diabetes mellitus according to the International Association of Diabetes in Pregnancy Study Groups criteria is associated with almost twice the risk of large-for-gestational-age babies, increased fetal adiposity, neonatal hyperinsulinemia and preeclampsia, and a 50% higher risk of preterm delivery and shoulder dystocia. The recent publication of the Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study provides further evidence regarding the influence of gestational diabetes mellitus on long-term maternal and infant health. This study clearly demonstrates that hyperglycemia in pregnancy, untreated and identified post hoc by the International Association of Diabetes in Pregnancy Study Groups criteria, carries a 41.5% risk of maternal prediabetes (odds ratio, 3.72; 95% confidence interval, 3.09-4.47) and 10.7% risk of type 2 diabetes (odds ratio, 7.63; 95% confidence interval, 5.33-10.95) after 11.4 years of follow up. Gestational diabetes mellitus was also associated with higher rates of childhood overweight and obesity (prevalence 39.3% with maternal gestational diabetes mellitus; odds ratio, 1.5; 95% confidence interval, 1.56-2.44). This article places these findings in the context of other recent studies that have demonstrated that interventions that include lifestyle measures and/or metformin offer a >50% reduction in the risk of women with gestational diabetes mellitus experiencing the development of overt diabetes mellitus after their index gestational diabetes mellitus pregnancy. Although prevention of obesity and prediabetes in offspring by pregnancy treatment of gestational diabetes mellitus has not been demonstrated to date, we argue that the immediate pregnancy benefits and opportunities for long-term improvements in maternal health justify a reevaluation of the current ambivalent approach taken by the American College of Obstetricians and Gynecologists to gestational diabetes mellitus diagnosis, which currently allow for a choice of alternative criteria. The Carpenter-Coustan or National Diabetes Data Group criteria, listed as preferred criteria by American College of Obstetricians and Gynecologists, markedly limit the frequency of gestational diabetes mellitus in comparison with the International Association of Diabetes in Pregnancy Study Groups criteria and limit the opportunity for immediate and long-term follow up and treatment. We consider that new information from the Hyperglycemia and Pregnancy Outcome Follow Up Study and other recent publications on long-term maternal and offspring risk provides compelling arguments for a more comprehensive approach to the promotion of maternal and infant health through all the life cycle.

Prevalence of hyperglycemia in pregnancy and influence of body fat on development of hyperglycemia in pregnancy among pregnant women in urban areas of Arusha region, Tanzania.

BACKGROUND: Hyperglycemia in pregnancy is a medical condition resulting from either pre-existing diabetes or insulin resistance developed during pregnancy. This study aimed to determine the prevalence of hyperglycemia in pregnancy and influence of body fat percentage and other determinants on developing hyperglycemia in pregnancy among women in Arusha District, Tanzania. METHODS: A cross-sectional study was conducted between March and December 2018 at selected health facilities in Arusha District involving 468 pregnant women who were not known to have diabetes before pregnancy. Blood glucose was tested by Gluco-Plus™ using the World Health Organization criteria at fasting and 2 h after consuming 75 g of glucose dissolved in 300 ml of water. Body fat was measured using a bioelectric impedance analyzer, mid-upper arm circumference using a regulated tape, weight using SECA™, blood pressure using a GT-868UF Geratherm™ machine, and height using a stadiometer. Demographic and maternal characteristics were collected through face to face interviews using a structured questionnaire. RESULTS: The participants' mean age was 28 years (SD ± 6), mid-upper arm circumference 27 cm (SD ± 3.7), body fat 33.72% (SD ± 7.2) and pre-pregnancy body mass index 25.6 kg/m2 (SD ± 5.5). One-third of participants had mid-upper arm circumferences ≥28 cm with 25% being overweight and 22.7% obese before pregnancy. Prevalence of hyperglycemia in pregnancy was 16.2% (n = 76) of which 13% had gestational diabetes and 3.2% diabetes in pregnancy. Hyperglycemia in pregnancy was significantly associated with body fat percentage (AOR 1.33; 95% CI: 1.22-1.44), family history of Type 2 diabetes mellitus (AOR 6.95, 95% CI: 3.11-15.55), previous delivery of babies ≥4 kg (AOR 2.3, 95% CI: 1.00-5.28), mid-upper arm circumference ≥ 28 cm (AOR 1.2, 95% CI: 1.09-1.32), and Type 2 diabetes mellitus symptoms (AOR 2.83, 95% CI: 1.53-6.92). CONCLUSION: The prevalence of hyperglycemia in pregnancy was high, particularly among women with history of delivering ≥4-kg babies, increased body fat, mid-upper arm circumference, symptoms and/or family history of Type 2 diabetes mellitus. These findings identify opportunities to further explore the utility of body fat percentage and other determinants for rapid screening and management of hyperglycemia in pregnancy.

Mid-trimester glycosylated hemoglobin levels (HbA1c) and its correlation with oral glucose tolerance test (World Health Organization 1999).

AIM: The aim of the present study was to assess the role of hemoglobin A1c (HbA1c) in screening of gestational diabetes mellitus (GDM) and to compare its efficacy with 75 g oral glucose tolerance test (OGTT) (World Health Organization [WHO]) screening criteria. METHODS: A prospective observational study was performed on a total of 260 women attending antenatal outpatient department of our hospital at 24-28 weeks of gestation. All women underwent 75-g OGTT testing, and WHO 1999 criteria was used for diagnosis of GDM. Also, a HbA1c test was performed for the same women. RESULTS: Prevalence of GDM was found to be 19.6% by OGTT. Mean HbA1c values in GDM was significantly higher than non-GDM. HbA1c correlated well with both fasting and 2 h postprandial levels but there was better correlation with 2-h postprandial level. CONCLUSION: The incidence of gestational diabetes is rising in South-East Asian countries, especially in India. HBA1c could be a potential screening test for GDM.

Hyperglycemia in pregnancy did not worsen the short-term outcomes of very preterm infants: a propensity score matching study.

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear. Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups. Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P < 0.05). Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization.

A Prediction Model of Preeclampsia in Hyperglycemia Pregnancy.

Purpose: To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care. Patients and Methods: The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24-29+6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the "rms" package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure. Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383-0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer-Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap re-samplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model. Conclusion: This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.

Prevalence of maternal hyperglycemic subtypes by race/ethnicity and associations between these subtypes with adverse pregnancy outcomes: Findings from a large retrospective multi-ethnic cohort in the United States.

AIMS: With the two-step gestational diabetes mellitus (GDM) screening approach, hyperglycemic subtypes can be identified. We aimed to investigate racial/ethnic differences in the prevalence of hyperglycemic subtypes and to examine the associations between these subtypes and adverse pregnancy outcomes. METHODS: In this retrospective cohort, 11,405 pregnancies were screened using the two-step approach. Hyperglycemic subtypes included: pregnancy-impaired glucose intolerance-I (PIGT-I), PIGT-II, GDM-I (abnormal post-load glucose only), and GDM-II (abnormal fasting & post-load glucose). Modified Poisson regressions with robust error variance were used to estimate age-adjusted prevalence ratios (PR) of hyperglycemic subtypes and multivariable-adjusted risk ratios (RR) of adverse pregnancy outcomes. RESULTS: The prevalence of hyperglycemic subtypes was higher in Asians (PIGT-I: 1.51 [95% confidence interval 1.35-1.69]; PIGT-II: 2.18 [1.78-2.68]; GDM-I: 2.55 [2.10-3.10]; GDM-II: 1.55 [1.08-2.21]) and Hispanics (PIGT-I: 1.32 [1.16-1.50]; PIGT-II: 2.07 [1.67-2.57]; GDM-I: 1.69 [1.35-2.13]; GDM-II: 2.68 [1.93-3.71]) than non-Hispanic Whites (NHW). Despite low GDM prevalence, Japanese and Koreans had higher PIGT prevalence than NHW. PIGT-II was positively associated with hypertensive disorders of pregnancy (1.19 [1.02-1.38]), large-for-gestational age (1.73 [1.37-2.18]), and preterm birth (PB, 1.33 [1.05-1.68]). PIGT-I (1.23 [1.04-1.45]) and GDM-I (1.56 [0.87-1.71]) were positively related to PB. CONCLUSIONS: The prevalence of hyperglycemic subtypes varies by race/ethnicity and they have distinct health implications.

Baicalin administration could rescue high glucose-induced craniofacial skeleton malformation by regulating neural crest development.

Hyperglycemia in pregnancy can increase the risk of congenital disorders, but little is known about craniofacial skeleton malformation and its corresponding medication. Our study first used meta-analysis to review the previous findings. Second, baicalin, an antioxidant, was chosen to counteract high glucose-induced craniofacial skeleton malformation. Its effectiveness was then tested by exposing chicken embryos to a combination of high glucose (HG, 50 mM) and 6 µM baicalin. Third, whole-mount immunofluorescence staining and in situ hybridization revealed that baicalin administration could reverse HG-inhibited neural crest cells (NCC) delamination and migration through upregulating the expression of Pax7 and Foxd3, and mitigate the disordered epithelial-mesenchymal transition (EMT) process by regulating corresponding adhesion molecules and transcription factors (i.e., E-cadherin, N-cadherin, Cadherin 6B, Slug and Msx1). Finally, through bioinformatic analysis and cellular thermal shift assay, we identified the AKR1B1 gene as a potential target. In summary, these findings suggest that baicalin could be used as a therapeutic agent for high glucose-induced craniofacial skeleton malformation.

Epidemiology of hyperglycemia during pregnancy in Ethiopia: prevalence, associated factors, and feto-maternal outcomes: systematic review and meta-analysis.

BACKGROUND: Hyperglycemia in pregnancy (HIP) is a significant medical complication affecting pregnant women globally and is considered a public health burden due to the negative outcomes it can cause for both mother and infant. The aim of this systematic review and meta-analysis was to examine the prevalence, risk factors, and feto-maternal outcomes of HIP in Ethiopia. METHODS: To gather relevant information for this study, both published and unpublished studies were searched for in several major databases, including PubMed, Embase, HINARI, Web of Science direct, and Google Scholar, as well as other sources. The Joanna Briggs Institute (JBI) tool was used to evaluate the methodological quality of the findings from these studies. Data was then extracted and summarized using a template in Microsoft Excel software, and the extracted data was analyzed using Stata software version 16.0. If significant heterogeneity was found between studies, subgroup analyses were conducted to further examine the data. RESULT: Eighteen studies were included in this systematic review and meta-analysis, involving a total sample size of 50,816 pregnant women in Ethiopia. The prevalence of HIP among pregnant women varied considerably across the primary studies, ranging from 0.4 to 26.2%. The pooled prevalence of HIP among pregnant women in Ethiopia was found to be 6.9% (95% C 2.2-11.6). Pregnant women with a family history of diabetes had 2.5 times higher odds of developing HIP compared to those without a family history of diabetes (OR = 2.49; 95% CI = 2.02, 2.96). However, there was no significant association found between HIP and maternal obesity (OR 2.31, 95% CI = 0.85, 3.78) or previous history of abortion (OR 3.89; 95% CI 0.85, 6.94). The common fetal outcomes associated with HIP were admission to the intensive care unit (46.2; 95% CI 27.4, 65.1), macrosomia (27.3%; 95% CI 9.4%, 45.1%), and preterm birth (16.9; 95% CI 12.5, 21.3). Additionally, hypertensive disorders of pregnancy (28.0%; 95% CI 15.2, 40.8) and operative delivery (51.4%; 95% CI 35.9, 66.8) were more common among women with HIP in Ethiopia. CONCLUSION: Although there was some variation between studies, the meta-analysis revealed that approximately seven out of 100 pregnant women in Ethiopia had HIP. A family history of diabetes was found to be a significant predictor of HIP in Ethiopia. Additionally, HIP was associated with various serious adverse outcomes for both mothers and infants in Ethiopia. These findings highlight the need for national guidelines to ensure that pregnant women are uniformly screened for HIP.

The Prognosis of Glutamic Acid Decarboxylase Antibodies in Women With Hyperglycemia in Pregnancy.

CONTEXT: We recently reported that the presence of glutamic acid decarboxylase antibodies (GADA) was not associated with large-for-gestational-age infants in women with hyperglycemia in pregnancy (HIP). OBJECTIVE: We explored the association between the presence of GADA and other HIP-related adverse pregnancy outcomes. METHODS: This observational prospective study, conducted at a university hospital in a suburb of Paris, France, included 1182 consecutive women with HIP measured for GADA at HIP care initiation between 2012 and 2017. Post hoc analyses for outcomes included gestational weight gain, insulin therapy, cesarean delivery, hypertensive disorders, small-for-gestational-age infant, prematurity, and neonatal hypoglycemia. RESULTS: Of the 1182 women studied, 87 (7.4%) had positive (≥ 1 IU/mL) GADA. Although socioeconomic, clinical, and biological characteristics were similar across women in the positive and negative GADA groups, higher fasting plasma glucose values during early HIP screening were observed in the former (5.5 ± 1.5 vs 5.2 ± 0.7 mmol/L respectively, P < .001). At HIP care initiation, fructosamine levels were higher in women with positive GADA (208 ± 23 vs 200 ± 18 µmol/L; P < .05). In the homeostatic model assessment, insulin resistance (HOMA-IR) and beta secretion (HOMA-B) rates were similar in both groups. Gestational weight gain and the rates of all adverse outcomes were similar in both groups except for cesarean delivery (18.4 and 27.3% for positive and negative GADA, respectively; adjusted odds ratio 0.49 [95% CI, 0.26-0.92], P = .026). CONCLUSION: Universal measurement of GADA in women with HIP highlighted that 7.4% had positive GADA. No association was observed between GADA and HIP-related adverse pregnancy outcomes, except a lower risk of cesarean delivery.

Relationship between serum NLRP3 along with its effector molecules and pregnancy outcomes in women with hyperglycemia.

OBJECTIVE: The study aims to investigate the levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in the mid-pregnancy in pregnant women with hyperglycemia, and explore the relationship between NLRP3, along with its effector molecules (Caspase-1, IL-1ß, and IL-18) and insulin resistance, as well as pregnancy outcomes. METHODS: The levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in three groups of pregnant women with gestational diabetes mellitus (GDM), pregestational diabetes mellitus (PGDM) and normal glucose tolerance (NGT) were measured in mid-pregnancy, and their relationship with insulin resistance and pregnancy outcomes was analyzed. The ROC curve was also used to evaluate the predictive value of serum NLRP3 inflammasome and its effector molecules for pregnancy outcomes. RESULTS: There were no statistical differences in the general clinical data of the three groups, and the concentrations of serum NLRP3 along with its effector molecules were higher in the GDM and PGDM groups than in the NGT group, and NLRP3 along with its effector molecules were positively correlated with fasting blood glucose, fasting insulin, and insulin resistance index in both groups (r > 0, p < .05). The incidence of preterm delivery, hypertensive disorders of pregnancy, premature rupture of membranes, neonatal hypoglycemia and macrosomia was significantly higher in both groups than in the NGT group (p < .05). The value of the combined serum NLRP3 and its effector molecules in mid-pregnancy to predict adverse pregnancy outcomes was highest, and the AUCs for the combined prediction of late hypertensive disorders of pregnancy, premature rupture of membranes, preterm delivery, neonatal hypoglycemia and macrosomia were 0.84 (95% CI 0.79-0.88, p < .001), 0.81 (95% CI 0.75-0.85, p < .001), 0.76 (95% CI 0.70-0.81, p < .001), 0.76 (95% CI 0.70-0.81, p < .001) and 0.72 (95% CI 0.63-0.81, p < .001), respectively. CONCLUSIONS: Increased serum NLRP3 along with its effector molecules in pregnant women with hyperglycemia are associated with the levels of insulin resistance and the subsequent development of adverse pregnancy outcomes.

Antenatal Corticosteroids and Their Effects on Maternal Glycemic Status: A Prospective Observational Study From an Indian Tertiary Referral Center.

Background Antenatal corticosteroids prevent multiple fetal complications and improve overall neonatal survival but at the cost of adverse effects including maternal hyperglycemia. This study aimed to understand the effect of antenatal corticosteroids on maternal glycemic control. Methodology This prospective observational study included 93 pregnant women with singleton pregnancies between 32 and 37 weeks gestation admitted for potential preterm labor. We assessed their glucose tolerance and categorized 56 participants with normal glucose tolerance in group 1, while 37 who had diabetes mellitus (DM) were categorized in group 2. Of the women with DM, 30 had gestational diabetes mellitus and seven had pre-existing type 2 diabetes. Betamethasone was administered as per the standard of care, two doses of 12 mg each, 24 hours apart. To assess the effect of corticosteroids on maternal blood glucose control, we monitored capillary blood glucose levels at specific time intervals for three days following the steroid administration. Fasting and post-meal glucose levels were checked a week after the administration of the steroid therapy, and it was observed that participants from group 1 had developed steroid-related hyperglycemia. Blood glucose levels ≥140 mg/dL were considered significant hyperglycemia, while blood glucose levels ≥160 mg/dL were considered severe hyperglycemia. Following this observation, we documented any modifications in the diabetes management plan during or after the corticosteroid treatment, including medical nutrition therapy, addition of oral anti-diabetic medications, commencement of insulin, or increasing insulin dosage. Standard software programs such as Microsoft Excel and SPSS (IBM Corp., Armonk, NY, USA) were used to analyze the collected data, summarize the findings, and identify any statistically significant relationships between the variables descriptive and inferential statistics, respectively. Results Participants from both groups demonstrated worsening glycemia requiring treatment involving insulin, following corticosteroid administration. The percentages of significant hyperglycemic participants from groups 1 and 2 were 72% and 92%, respectively. Severe hyperglycemia was seen in 43% and 84% of the participants from groups 1 and 2, respectively. An intervention involving insulin administration was required by group 2 participants with pre-existing diabetes within six hours of steroid administration, followed by those with gestational diabetes requiring intervention within 12-24 hours, and by group 1 participants at 24-48 hours. One week after the administration of antenatal corticosteroids, hyperglycemia persisted in 20 (35.71%) of the 56 participants in group 1, of which six (30%) participants required insulin therapy. On the other hand, 18 (48.64%) participants from group 2 required additional insulin therapy after a week of administration of steroids when compared to pre-steroid administration status. Conclusions The findings of this study demonstrate that antenatal betamethasone therapy resulted in worsening hyperglycemia in most pregnant women, regardless of pre-existing glycemic status. These findings highlight the need for close monitoring of blood glucose levels and potential adjustments to medication regimens following antenatal betamethasone administration, irrespective of the pre-existing glycemic status.

Association between changes in glycosylated hemoglobin during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy.

OBJECTIVE: To explore the relationship between changes in glycated hemoglobin (HbA1c) during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy (HIP). RESEARCH DESIGN AND METHODS: A total of 1,057 pregnant women who underwent serum HbA1c and delivered at Women's Hospital, Zhejiang University School of Medicine from May 2022 to March 2023, were included in this study. They were divided into four groups. Associations were evaluated using multivariate logistic regression analysis. RESULTS: In our study, an upward trend in HbA1c levels in the second trimester (HbA1c_S) and third trimester (HbA1c_T) among women without HIP was demonstrated. Multivariate logistics regression analysis showed significant associations: Pregnant women with HbA1c_S<5.5 %, HbA1c_T≥6.1 %, or with HbA1c_S≥5.5 %, HbA1c_T<6.1 % had a significant correlation with hypertensive disorders of pregnancy (HDP) (aOR:2.72, 95 %CI=1.24-5.97；aOR:2.59, 95 %CI=1.15-5.84). Furthermore, for each 1 % increase in the difference value of HbA1c between the second and third trimesters, the risk of HDP increased about 1.96 times, and the risk of delivering a large-for-gestational-age baby increased about 1.30 times. CONCLUSION: Among pregnant women without HIP, elevated HbA1c levels in the second or third trimester are associated with increased risks of adverse pregnancy outcomes.