GDM Pregnancies Research Articles

First trimester maternal serum PAPP-A and free β-hCG levels and risk of SGA or LGA in women with and without GDM

BackgroundMaternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls.MethodsAltogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking.ResultsIn pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5–4.7) and 2.2 (95% CI 1.4–3.5) in the GDM group and 3.8 (95% CI 3.0–4.9) and 2.8 (95% CI 2.3–3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8–3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1–2.5) for LGA.ConclusionAssociation with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies.

Special Supplemental Nutrition Program for Women, Infants, and Children Enrollment and Adverse Pregnancy Outcomes Among Nulliparous Individuals.

To evaluate the relationship between changes in Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) enrollment during pregnancy from 2016 to 2019 and rates of adverse pregnancy outcomes in U.S. counties in 2019. We conducted a serial, cross-sectional ecologic study at the county level using National Center for Health Statistics natality data from 2016 to 2019 of nulliparous individuals eligible for WIC. The exposure was the change in county-level WIC enrollment from 2016 to 2019 (increase [more than 0%] vs no change or decrease [0% or less]). Outcomes were adverse pregnancy outcomes assessed in 2019 and included maternal outcomes (ie, gestational diabetes mellitus [GDM], hypertensive disorders of pregnancy, cesarean delivery, intensive care unit [ICU] admission, and transfusion) and neonatal outcomes (ie, large for gestational age [LGA], small for gestational age [SGA], preterm birth, and neonatal intensive care unit [NICU] admission). Among 1,945,914 deliveries from 3,120 U.S. counties, the age-standardized rate of WIC enrollment decreased from 73.1 (95% CI, 73.0-73.2) per 100 live births in 2016 to 66.1 (95% CI, 66.0-66.2) per 100 live births in 2019, for a mean annual percent change decrease of 3.2% (95% CI, -3.7% to -2.9%) per year. Compared with individuals in counties in which WIC enrollment decreased or did not change, individuals living in counties in which WIC enrollment increased had lower rates of maternal adverse pregnancy outcomes, including GDM (adjusted odds ratio [aOR] 0.71, 95% CI, 0.57-0.89), ICU admission (aOR 0.47, 95% CI, 0.34-0.65), and transfusion (aOR 0.68, 95% CI, 0.53-0.88), and neonatal adverse pregnancy outcomes, including preterm birth (aOR 0.71, 95% CI, 0.56-0.90) and NICU admission (aOR 0.77, 95% CI, 0.60-0.97), but not cesarean delivery, hypertensive disorders of pregnancy, or LGA or SGA birth. Increasing WIC enrollment during pregnancy at the county level was associated with a lower risk of adverse pregnancy outcomes. In an era when WIC enrollment has decreased and food and nutrition insecurity has increased, efforts are needed to increase WIC enrollment among eligible individuals in pregnancy.

ITRAQ proteomics analysis of placental tissue with gestational diabetes mellitus.

Gestational diabetes mellitus is an endocrine and metabolic disorder that appears for the first time during pregnancy and causes varying degrees of short- and/or long-term effects on the mother and child. The etiology of the disease is currently unknown and isobaric tags for relative and absolute quantitation proteomics approach, the present study attempted to identify potential proteins in placental tissues that may be involved in the pathogenesis of GDM and adverse foetal pregnancy outcomes. Pregnant women with GDM hospitalised were selected as the experimental group, and pregnant women with normal glucose metabolism as the control group. The iTRAQ protein quantification technology was used to screen the differentially expressed proteins between the GDM group and the normal control group, and the differentially expressed proteins were analysed by GO, KEGG, PPI, etc., and the key proteins were subsequently verified by western blot. Based on the proteomics of iTRAQ, we experimented with three different samples of placental tissues from GDM and normal pregnant women, and the total number of identified proteins were 5906, 5959, and 6017, respectively, which were similar in the three different samples, indicating that the results were reliable. Through the Wayne diagram, we found that the total number of proteins coexisting in the three groups was 4475, and 91 differential proteins that could meet the quantification criteria were strictly screened, of which 32 proteins were up-regulated and 59 proteins were down-regulated. By GO enrichment analysis, these differential proteins are widely distributed in extracellular membrane-bounded organelle, mainly in extracellular exosome, followed by intracellular vesicle, extracellular organelle. It not only undertakes protein binding, protein complex binding, macromolecular complex binding, but also involves molecular biological functions such as neutrophil degranulation, multicellular organismal process, developmental process, cellular component organization, secretion, regulated exocytosis. Through the analysis of the KEGG signaling pathway, it is found that these differential proteins are mainly involved in HIF-1 signaling pathway, Glycolysis/Gluconeogenesis, Central carbon metabolism in cancer, AMPK signaling pathway, Proteoglycans in cancer, Protein processing in endoplasmic reticulum, Thyroid cancer, Alcoholism, Glucagon signaling pathway. This preliminary study helps us to understand the changes in the placental proteome of GDM patients, and provides new insights into the pathophysiology of GDM.

Demystifying Glycemic Variability in GDM Pregnancies: A Cross-Sectional Observational Study

Demystifying Glycemic Variability in GDM Pregnancies: A Cross-Sectional Observational Study

Non-hypertensive gestational diabetes mellitus: Placental histomorphology and its association with perinatal outcomes

IntroductionGestational diabetes mellitus (GDM) exerts a great impact on the placenta and reflects changes on placentas both morphological and functionally. The aims of this study are to evaluate the prevalence of placental histopathological lesions in pregnancies complicated by GDM compared to gestational age-matched controls, and their association with maternal and fetal complications. MethodsFifty-four singleton GDM-complicated pregnancies were recruited and compared to 33 consecutive normal pregnancies. Two pathologists, blinded to all clinical data, reviewed and evaluated all histological samples of the placentas in accordance with Amsterdam criteria. Relevant demographic, clinical data and primary birth outcomes were recorded. ResultsA myriad of histomorphological abnormalities, including chronic inflammation (n = 9/54, p = 0.031), histological chorioamnionitis (n = 23/54, p < 0.001), umbilical/chorionic vasculitis (n = 9/54, p = 0.031), changes related to maternal vascular malperfusion (n = 22/54, p = 0.003), chorangiosis (n = 10/54, p = 0.046) and villous dysmaturity (n = 9/54, p = 0.012) were observed more frequently in the GDM placentas compared to the controls. Additionally, GDM significantly increased the risk of fetal complications, including macrosomia/fetal growth restriction (n = 13/54, p = 0.004). DiscussionHistoarchitectural abnormalities were observed more frequently in placentas of GDM pregnancies compared to the controls. Our findings support the hypothesis that diabetic-induced damage in the placental function may be associated with the increased in fetal growth disorders in GDM-complicated pregnancies.

Umbilical cord mesenchymal stem cells from gestational diabetes show impaired ability to up-regulate paracellular permeability from sub-endothelial niche.

In vitro studies have shown that Wharton's jelly mesenchymal stem cells (WJ-MSCs) can cross umbilical and uterine endothelial barriers and up-regulate endothelial junctional integrity from sub-endothelial niches. This pericytic behaviour may be lost in pregnancies complicated by gestational diabetes (GDM), where increased vascular permeability and junctional disruption are reported. The aim of the present study was to investigate whether WJ-MSCs isolated from GDM pregnancies displayed any changes in morphology, proliferation, VEGF-A secretion, and their ability to influence paracellular junctional composition and permeability. WJ-MSCs were isolated from human umbilical cords from normal pregnancies (nWJ-MSCs, n=13) and those complicated by GDM (gWJ-MSCs), either diet-controlled (d-GDM, n=13) or metformin-treated (m-GDM, n=9). We recorded that 4-fold more WJ-MSCs migrated from m-GDM, and 2.5-fold from d-GDM cord samples compared with the normal pregnancy. gWJ-MSCs showed a less predominance of spindle-shaped morphology and secreted 3.8-fold more VEGF-A compared with nWJ-MSCs. The number of cells expressing CD105 (Endoglin) was higher in gWJ-MSCs compared with nWJ-MSCs (17%) at P-2. The tracer leakage after 24 h across the HUVEC + gWJ-MSCs bilayer was 22.13% and 11.2% higher in the m-GDM and d-GDM, respectively, HUVEC + nWJ-MSCs. Transfection studies with siRNAs that target Endoglin were performed in n-WJ-MSCs; transfected cells were co-cultured with HUVEC followed by permeability studies and VE-cadherin analyses. Loss of Endoglin also led to increased VEGF-A secretion, increased permeability and affected endothelial stabilization. These results reinforce the pericytic role of nWJ-MSCs to promote vascular repair and the deficient ability of gWJ-MSCs to maintain endothelial barrier integrity.

Implementing care for women with gestational diabetes after delivery-the challenges ahead.

Gestational diabetes (GDM), defined as glucose intolerance during pregnancy, affects one in six pregnancies globally and significantly increases a woman's lifetime risk of type 2 diabetes mellitus (T2DM). Being a relatively young group, women with GDM are also at higher risk of developing diabetes related complications (e.g., cardiovascular disease, non-alcoholic fatty liver disease) later in life. Children of women with GDM are also likely to develop GDM and this perpetuates a cycle of diabetes, escalating our current pandemic of metabolic disease. The global prevalence of GDM has now risen by more than 30% over the last two decades, making it an emerging public health concern. Antepartum management of maternal glucose is unable to fully mitigate the associated lifetime cardiometabolic risk. Thus, efforts may need to focus on improving care for women with GDM during the postpartum period where prevention or therapeutic strategies could be implemented to attenuate progression of GDM to DM and its associated vascular complications. However, strategies to provide care for women in the postpartum period often showed disappointing results. This has led to a missed opportunity to halt the progression of impaired glucose tolerance/impaired fasting glucose to DM in women with GDM. In this review, we examined the challenges in the management of women with GDM after delivery and considered how each of these challenges are defined and could present as a gap in translating evidence to clinical care. We highlighted challenges related to postpartum surveillance, postpartum glucose testing strategies, postpartum risk factor modification, and problems encountered in engagement of patients/providers to implement interventions strategies in women with GDM after delivery. We reasoned that a multisystem approach is needed to address these challenges and to retard progression to DM and cardiovascular disease (CVD) in women with GDM pregnancies. This is very much needed to pave way for an improved, precise, culturally sensitive and wholistic care for women with GDM.

Autoantibodies predict type 1 diabetes after gestational diabetes - a 23-year cohort study.

To study the predictive value of autoantibodies for type 1 (T1DM) and type 2 (T2DM) diabetes morbidity after gestational diabetes (GDM) in a 23-year follow-up study. Prospective population-based cohort study. We studied 391 women with GDM, and 391 age- and parity-matched controls, who delivered in 1984-1994. Four autoantibodies were analysed in first-trimester blood samples: islet cell autoantibodies (ICAs), glutamic acid decarboxylase autoantibodies (GADAs), insulin autoantibodies (IAAs) and insulinoma-associated antigen-2 autoantibodies (IA-2As). Two follow-up questionnaires (1995-1996, 2012-2013) were sent to assess development of T1DM and T2DM. Predictive value of autoantibodies and clinical factors were analysed by conditional linear regression and ROC analyses. Single autoantibody positivity was detected in 12% (41/342) of the GDM cohort and in 2.3% (8/353) of the control cohort. In the GDM cohort, 2.6% (9/342) tested positive for two autoantibodies and 2.3% (8/342) for three autoantibodies, whereas only one subject in the control cohort had two autoantibodies. ICA positivity was found in 12.5% of the cases, followed by GADA (6.0%), IA-2A (4.9%) and IAA (1.2%). In the control cohort, GADA positivity was found in 1.4%, IA-2A in 0.8%, IAA in 0.6%, and ICA in 0.3% of the subjects. Detection of ICA, GADA and/or IA-2A autoantibodies decreased T1DM-free survival time and time to diagnosis. All subjects with three positive autoantibodies developed T1DM within seven years from the GDM pregnancy. Development of T2DM after GDM occurred independent of autoantibody positivity. Development of T1DM can be reliably predicted with GADA and ICA autoantibodies during early pregnancy.

Neonatal adiposity is associated with microRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood, a discovery analysis.

Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential. There were 279 mother-neonate pairs with all phenotypic data (normal glucose tolerant NGT = 148, gestational diabetes mellitus GDM = 131). Neonates with adiposity were those in the highest tertile (T3) of sex-specific sum of skinfolds and those without adiposity (lean) in the lowest tertile T1 of NGT pregnancies. We studied ADsEV miRNAs in 76 and 51 neonates with and without adiposity respectively and their mothers based on power calculations (68 NGT and 59 GDM pregnancies). ADsEV miRNAs from maternal and cord blood plasma samples were profiled on Agilent 8*60 K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean groups was studied before and after adjustment for maternal GDM, adiposity, and vitamin B12-folate status. Multiple miRNAs were common in maternal and cord blood and positively correlated. We identified 24 maternal and 5 cord blood miRNAs differentially expressed (discovery p ≤ 0.1) in the adipose group in unadjusted, and 19 and 26, respectively, in the adjusted analyses. Even though DE miRNAs were different in maternal and cord blood, they targeted similar adipogenic pathways (e.g., the forkhead box O (FOXO) family of transcription factors, mitogen‑activated protein kinase (MAPK) pathway, transforming growth factor beta (TGF-β) pathway). Maternal GDM and adiposity were associated with many DE ADsEV miRNAs. Our results suggest that the ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appear to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.

Postpartum defects in inflammatory response after gestational diabetes precede progression to type 2 diabetes: a nested case-control study within the SWIFT study

BackgroundGestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are nearly ten times more likely to develop type 2 diabetes than women with uncomplicated pregnancies. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression. AimTo comprehensively characterize the postpartum profiles of women shortly after a GDM pregnancy and identify key mechanisms responsible for the progression to overt type 2 diabetes using multi-dimensional approaches. MethodsWe conducted a nested case-control study of 200 women from the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT) to examine biochemical, proteomic, metabolomic, and lipidomic profiles at 6–9 weeks postpartum (baseline) after a GDM pregnancy. At baseline and annually up to two years, SWIFT administered research 2-hour 75-gram oral glucose tolerance tests. Women who developed incident type 2 diabetes within four years of delivery (incident case group, n = 100) were pair-matched by age, race, and pre-pregnancy body mass index to those who remained free of diabetes for at least 8 years (control group, n = 100). Correlation analyses were used to assess and integrate relationships across profiling platforms. ResultsAt baseline, all 200 women were free of diabetes. The case group was more likely to present with dysglycemia (e.g., impaired fasting glucose levels, glucose tolerance, or both). We also detected differences between groups across all omic platforms. Notably, protein profiles revealed an underlying inflammatory response with perturbations in protease inhibitors, coagulation components, extracellular matrix components, and lipoproteins, whereas metabolite and lipid profiles implicated disturbances in amino acids and triglycerides at individual and class levels with future progression. We identified significant correlations between profile features and fasting plasma insulin levels, but not with fasting glucose levels. Additionally, specific cross-omic relationships, particularly among proteins and lipids, were accentuated or activated in the case group but not the control group. ConclusionsOverall, we applied orthogonal, complementary profiling techniques to uncover an inflammatory response linked to elevated triglyceride levels shortly after a GDM pregnancy, which is more pronounced in women who progress to overt diabetes.

Sulforaphane induced NRF2 activation in obese pregnancy attenuates developmental redox imbalance and improves early-life cardiovascular function in offspring

In adverse pregnancy a perturbed redox environment is associated with abnormal early-life cardiovascular development and function. Previous studies have noted alterations in the expression and/or activity of Nuclear Factor E2 Related Factor 2 (NRF2) and its antioxidant targets during human gestational diabetic (GDM) pregnancy, however to our knowledge the functional role of NRF2 in fetal ‘priming’ of cardiovascular dysfunction in obese and GDM pregnancy has not been investigated. Using a murine model of obesity-induced glucose dysregulated pregnancy, we demonstrate that NRF2 activation by maternal sulforaphane (SFN) supplementation normalizes NRF2-linked NQO1, GCL and CuZnSOD expression in maternal and fetal liver placental and fetal heart tissue by gestational day 17.5. Activation of NRF2 in utero in wild type but not NRF2 deficient mice improved markers of placental efficiency and partially restored fetal growth. SFN supplementation was associated with reduced markers of fetal cardiac oxidative stress, including Nox2 and 3-nitrotyrosine, as well as attenuation of cardiac mass and cardiomyocyte area in male offspring by postnatal day 52 and improved vascular function in male and female offspring by postnatal day 98. Our findings are the first to highlight the functional consequences of NRF2 modulation in utero on early-life cardiovascular function in offspring, demonstrating that activation of NRF2 affords cardiovascular protection in offspring of pregnancies affected by redox dysregulation.

66-LB: Poor Sleep Is Correlated with Higher Parenting Stress in Women Who Have Had Gestational Diabetes

Background: Theoretically, women who have had GDM are likely to have increased stress levels following pregnancy related to parental stress exacerbated by concerns about personal health (e.g., development of T2DM). Such stress may negatively impact sleep, however, the relationship between parenting stress and sleep in women who have had GDM has not been well investigated. Therefore, the purpose of the study was to explore the correlations between sleep and parenting stress in people who have had GDM. Methods: Twenty-six woman (ages: 34.22 ± 3.51 years; ethnicity: African American [38.46%], Hispanic [30.77%], Caucasian [19.23%], and Asian [11.54%]; A1C: 5.78 ± .98 %; BMI: 36.28 ± 10.70; age of child from GDM pregnancy: 6.07 ± 3.95 months; number of children: range1-6; months of postpartum: 6.06 ± 3.96) who had GDM on the previous pregnancy completed self-reported questionnaires. These included Parenting Stress Index (PSI-4, SF), PROMIS Global Health-Physical (v.1.2;2a), PROMIS Fatigue (v.1.0;8a), PROMIS Sleep Disturbance (v.1.0;8b), and PROMIS Sleep-Related Impairment (v.1.0;8a). The Spearman’s correlation was used to analyze data using STATA 17.0. Results: The mean total score on the Parenting Stress Index was positively correlated with PROMIS Fatigue (Spearman’s r = 0.61, p &amp;lt; .01); PROMIS Sleep Disturbance (r = 0.61, p &amp;lt; .001); and PROMIS Sleep-Related Impairment (r= 0.57, p &amp;lt; .001). On the other hand, the mean total score on the Parenting Stress Index was negatively correlated with PROMIS Global Health-Physical (r = -0.58, p &amp;lt; .01), and was not correlated with A1C and BMI. Conclusion: In this glucose intolerant group of women with previous GDM, parenting stress was correlated with fatigue alone with sleep disturbances and impairments. In addition, parenting stress was negatively correlated with individuals’ assessment of their health. Finding suggested that it is necessary to explore the associations between parenting stress, sleep, and glucose metabolism in women who have had GDM. Disclosure M. Park: None. Y. Song: None. M. Chu: None. L. T. Quinn: None.

Role of ultrasonographic measurement of the fetal epicardial fat pad and cardiac interventricular septal thickness in predicting the outcome and prevent various complications of gestational diabetes mellitus

BackgroundGestational diabetes mellitus (GDM) is one of the most common medical conditions affecting pregnancy and increasing the risk for maternal and perinatal complications. The present study aimed at determining the role of ultrasonographic measurement of fetal epicardial fat pad thickness (f EFT) and fetal cardiac interventricular septal thickness (f IVST) at 24–32 weeks of gestation in the prediction of GDM.ResultsA prospective observational case–control study was conducted including a total of 35 GDM patients and 35 normal pregnancies who were subjected to ultrasonographic measurement of the f EFT and f IVST at 24–32 weeks of gestation. Statistical analysis and the receiver operating characteristic curves were used to find out the cutoff value, sensitivity, specificity and diagnostic accuracy of these two parameters for the prediction of GDM. When an f EFT value of 1.3 was accepted as a cutoff value, GDM could be predicted with a sensitivity of 68.6% and specificity of 91.4%, PPV of 88.9%, NPV of 74.4% and diagnostic accuracy of 80%. When an f IVST value of 2.6 was accepted as a cutoff value, GDM could be predicted with a sensitivity of 80%, specificity of 77.14%, PPV of 77.8%, NPV of 79.4% and diagnostic accuracy of 78.5%.ConclusionThe ultrasonographic measurements of fetal epicardial fat pad thickness and fetal cardiac interventricular septal thickness were statistically significantly higher in GDM pregnancies (p value < 0.0001) as compared to the controls. Thus, these two parameters can serve as excellent ultrasonographic markers in the prediction of GDM.

Hyperglycemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model.

Hyperglycemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycemia that negatively impacts short- and long-term health of mother and child. However, relationships between severity and timing of pregnancy hyperglycemia and postpartum outcomes have not been systemically investigated. We investigated the impact of hyperglycemia developing during pregnancy (gestational diabetes mellitus, GDM) or already present pre-mating (pre-gestational diabetes mellitus, PDM) on maternal health and pregnancy outcomes. GDM and PDM were induced in C57BL/6NTac mice by combined 60% high fat diet (HF) and low dose streptozotocin (STZ). Animals were screened for PDM prior to mating, all underwent an OGTT on gestational day (GD)15. Tissues were collected at GD18 or at postnatal day (PN)15. Among HFSTZ-treated dams, 34% developed PDM and 66% developed GDM, characterized by impaired glucose-induced insulin release and inadequate suppression of endogenous glucose production. No increased adiposity or overt insulin resistance was observed. Furthermore, markers of non-alcoholic fatty liver disease (NAFLD) were significantly increased in PDM at GD18 and were positively correlated with basal glucose levels at GD18 in GDM dams. By PN15, NAFLD markers were also increased in GDM dams. Only PDM affected pregnancy outcomes such as litter size. Our findings indicate that GDM and PDM, resulting in disturbances of maternal glucose homeostasis, increase the risk of postpartum NAFLD development, related to the onset and severity of pregnancy hyperglycemia. These findings signal a need for earlier monitoring of maternal glycemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans. KEY POINTS: We studied the impact of high-fat diet/streptozotocin induced hyperglycemia in pregnancy (HIP) in mice and found that this impaired glucose tolerance and insulin release. Litter size and embryo survival were compromised by pre-gestational, but not by gestational diabetes. Despite postpartum recovery from hyperglycemia in a majority of dams, liver disease markers were further elevated by PN15. Maternal liver disease markers were associated with the severity of hyperglycemia at GD18. The association between hyperglycemic exposure and NAFLD signal a need for more rigorous monitoring and follow-up of maternal glycemia and health in diabetic pregnancy in humans. Abstract figure legend Streptozotocin and high fat diet were used to induce GDM in female BL6/NTac mice. Pregnant dams underwent an OGTT at GD15 to confirm GDM diagnosis. By GD18, dams were hyperglycemic and showed a reduction in pancreatic beta cells. By PN15, dams additionally had developed an increase in NAFLD markers, despite the majority of the dams having recovered from hyperglycemia. This article is protected by copyright. All rights reserved.

Significant risk of repeat adverse outcomes in recurrent gestational diabetes pregnancy: a retrospective cohort study

BackgroundThe risk of adverse outcomes in recurrent GDM pregnancy has not been well documented, particularly in women who have already had an adverse outcome. The aim of this study was to compare the risk of recurrent adverse delivery outcome (ADO) or adverse neonatal outcome (ANO) between consecutive gestational diabetes (GDM) pregnancies.MethodsIn this retrospective study of 424 pairs of consecutive (“index” and “subsequent”) GDM pregnancies, we compared the risk of ADO (instrumental delivery, emergency Caesarean section) and ANO (large for gestational age (LGA and small for gestational age (SGA)) in women with and without a history of adverse outcome in their index pregnancy.ResultsSubsequent pregnancies had higher rates of elective Caesarean (30.4% vs 17.0%, p < 0.001) and lower rates of instrumental delivery (5% vs 13.9%, p < 0.001), emergency Caesarean (7.1% vs 16.3%, p < 0.001) and vaginal delivery (62.3% vs 66.3%, p = 0.01). Index pregnancy adverse outcome was associated with a higher risk of repeat outcome: RR 3.09 (95%CI:1.30,7.34) for instrumental delivery, RR 2.20 (95%CI:1.06,4.61) for emergency Caesarean, RR 4.55 (95%CI:3.03,6.82) for LGA, and RR 5.01 (95%CI:2.73,9.22) for SGA). The greatest risk factor for subsequent LGA (RR 3.13 (95%CI:2.20,4.47)) or SGA (RR 4.71 (95%CI:2.66,8.36)) was having that outcome in the index pregnancy.ConclusionA history of an adverse outcome is a powerful predictor of the same outcome in the subsequent GDM pregnancy. These high-risk women may warrant more directed management over routine GDM care such as altered glucose targets or increased frequency of ultrasound assessment.

Maternal, placental, and fetal Insulin-Like Growth Factor-I (IGF-1) and IGF Binding proteins (IGFBPs) in Diabetic pregnancies: Effects on fetal growth and birth size.

Introduction: During gestation, IGF1 secretion and availability in the maternal blood and at the maternal-fetal interface is mainly regulated by IGF-binding proteins (IGFBP) such as IGFBP-1 synthesized by the decidua. Data about the interaction between maternal, placental, and fetal IGF1/IGFBP in relation to fetal growth and newborn size during diabetic pregnancy (gestational Diabetes (GDM) and Type 1 DM (T1DM) is not clear. Aim of the study and Methods: We reviewed the research papers published in Pubmed, Google scholar, Research gate, and Scopus in the past 20 years on the relationship between maternal, placental, and fetal/infantile/ IGF1/IGFBP-1 in relation to birth size in pregnancies associated with maternal diabetes. Results: Twenty-eight research papers were selected and reviewed (patients’ number = 1902). In GDM pregnancies, higher maternal IGF1 levels and/or its availability due to lower IGFBP1 levels can increase the size (weight) and functions of the placenta. These include the upregulation of specific placental amino acid transporter isoforms and GLUT-1, stimulation of mTOR signaling which stimulates protein synthesis, increasing mitochondrial functions, and accelerating nutrient transport which significantly contributes to fetal growth and newborn birth size. On the other hand, in pregnant women with T1DM, lower maternal IGF1 is associated with subsequent underweight placenta and lower birthweight.

Using flash glucose monitoring in pregnancies in routine care of patients with gestational diabetes mellitus: a pilot study

AimFlash glucose monitoring (FGM) has been approved for the care of pregnant women with preexisting diabetes since 2017. However, its use in gestational diabetes (GDM) has been critically discussed. Inaccuracy and missing recommendations for target values are the main arguments against the use of FGM in GDM. To date, there is a lack of data to justify routine use of FGM in GDM pregnancies. Consequently, this new technology has been withheld from GDM-patients. Aim of our pilot study was to analyze the impact of FGM use on pregnancy outcomes, patient’s satisfaction and to confirm the safe use in GDM pregnancies.MethodsCohort study of 37 FGM-managed GDM pregnancies compared with 74 matched women using self-monitoring of blood glucose (SMBG). Group comparison using nonparametric testing concerning patients characteristic and perinatal outcome focusing on adverse outcomes (preeclampsia, preterm delivery, large for gestational age, C-sections, neonatal intensive care unit admission, hyperbilirubinemia and hypoglycemia). Evaluation of patient’s treatment satisfaction using the “Diabetes Treatment Satisfaction Questionnaire change” (DTSQc) and patient interviews.ResultsNo significant differences in patient’s characteristics despite gestational age at diagnosis (FGM with 20 vs. SMBG with 25 weeks). No difference in gestational weight gain, HbA1c progression and perinatal outcome. Treatment satisfaction obtained by the DTSQc revealed a high level of satisfaction with FGM use.ConclusionFGM use was well accepted and did not affect perinatal outcome. Use of FGM during pregnancy is safe and non-inferior to the management with SBGM. FGM should be considered as an option in the management of GDM patients.

The ANGPTL3-4-8 Axis in Normal Gestation and in Gestational Diabetes, and Its Potential Involvement in Fetal Growth.

Dyslipidemia in gestational diabetes has been associated with worse perinatal outcomes. The ANGPTL3-4-8 axis regulates lipid metabolism, especially in the transition from fasting to feeding. In this study, we evaluated the response of ANGPTL3, 4, and 8 after the intake of a mixed meal in women with normal glucose tolerance and gestational diabetes, and we assessed their gene expressions in different placental locations. Regarding the circulating levels of ANGPTL3, 4, and 8, we observed an absence of ANGPTL4 response after the intake of the meal in the GDM group compared to its presence in the control group. At the placental level, we observed a glucose tolerance-dependent expression pattern of ANGPTL3 between the two placental sides. When we compared the GDM pregnancies with the control pregnancies, a downregulation of the maternal side ANGPTL3 expression was observed. This suggests a dysregulation of the ANGPTL3-4-8 axis in GDM, both at the circulating level after ingestion and at the level of placental expression. Furthermore, we discerned that the expressions of ANGPTL3, 4, and 8 were related to birth weight and placental weight in the GDM group, but not in the control group, which suggests that they may play a role in regulating the transplacental passage of nutrients.

Longitudinal multistate analysis: influence of gestational diabetes on the transition to prediabetes among NYC adolescents

Nearly one-third of adolescent girls in the U.S. have prediabetes, with implications for the future rise of cardiovascular-related complications during pregnancy. Gestational diabetes is strongly associated with later life type 2 diabetes (T2DM) and cardiovascular risk, but its influence on the transition from normoglycemia to prediabetes is not well characterized. This study explores the influence of gestational diabetes on the transition to from normoglycemia to pre-diabetes in a population-based cohort of New York City (NYC) adolescents aged 10 to 19 years. We used data from the APPLE Cohort, a retrospective cohort of linked 2009-2017 birth certificate, hospital discharge, and NYC A1c Registry test data. Adolescents aged 10-19 with no history of type 2 diabetes comprised the baseline cohort among (n=39,874). We formulated a three-state multistate Markov model (normoglycemia (HbA1c< 5.7), pre-diabetes (5.7-6.4) and censored) for examining the influence of gestational diabetes (GDM) on the longitudinal transition from nomoglycemia to pre-diabetes. A total of 1.5% (N=602) pregnancies were complicated by GDM. In normoglycemia pregnancies uncomplicated by GDM, the probability of being in a pre-diabetes state at the next 12 month interval was 7% compared to 14% among those with GDM pregnancies. Similarly, the hazard ratio (HR) for the influence of GDM on the transition from normoglycemia to prediabetes was 1.9 (95% Confidence Interval: 1.3, 2.9). Adjusting for race/ethnicity, obesity and nativity, GDM pregnancies were still nearly 2 times more likely to transition to a prediabetes state (aHR 1.7, 95% CI: 1.2, 2.6) at an HbA1c test in the next 12 month interval compared to non-GDM pregnancies. While adolescents have a relatively low burden of T2DM, those who experience GDM are more likely to advance in disease progression sooner than their non-GDM counterparts. Results suggest the need for enhanced screening and monitoring of GDM adolescent patients following pregnancy to manage disease progression.

Clinician-identified barriers and potential solutions to diabetes prevention after gestational diabetes

Gestational diabetes (GDM) confers a lifelong risk for type 2 diabetes (T2D). Yet, key T2D prevention strategies in the postpartum period are often thwarted by competing clinician and patient demands. We aimed to explore clinician perceptions of barriers to T2D prevention for both clinicians and patients with a prior GDM pregnancy, and to identify potential solutions in the postpartum period.