Gestational Diabetes Mellitus Pregnancies Research Articles

Short-term health and economic burden of gestational diabetes mellitus in Mexico: A modeling study

AimTo estimate the annual burden of gestational diabetes mellitus (GDM) in Mexico. MethodsA model was built to conduct estimates from a healthcare system perspective, namely, the incremental costs of GDM pregnancy compared with non-GDM pregnancy from the first trimester until childbirth. The model used probabilities from the literature and surveys, and costs obtained from the Ministry of Health and national healthcare institutions. Scenario analyses were performed to estimate the GDM burden at different levels of incidence. ResultsAlthough a non-GDM pregnancy cost on average USD 1880.6 (low risk was USD 1043.9 and high risk was USD 1673.5), a pregnancy with GDM cost USD 2934.9. Therefore, the total additional cost was USD 1576.2 per case. Given the considerable variability of the GDM incidence in Mexico, the total burden could range from USD 86.8 to USD 827.4 million per year. ConclusionsGDM is one of the most frequent complications of pregnancy, but research has been insufficient regarding its epidemiological and economic burden in Latin America. This paper shows that the GDM economic burden in Mexico is substantial despite only accounting for short-term medical costs. Further research to assess the GDM incidence and evaluate its long-term consequences from a broader societal perspective in Mexico is recommended.

Soluble CD163 and TWEAK in early pregnancy gestational diabetes and later glucose intolerance.

Gestational diabetes mellitus (GDM) is today universally diagnosed during late pregnancy. Treating hyperglycaemia during pregnancy reduces the risk of complications, the effect of interventions is however limited due to the late diagnosis. It is thus important to identify biomarkers reaching a high precision for GDM development in early pregnancy. Here we aim to investigate soluble CD163 (sCD163) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in early pregnancy GDM and their association to the development of later glucose intolerance. In this case-control study, women diagnosed with GDM in early pregnancy (n = 70) at Lund University Hospital, Lund, Sweden in 2011–2015 were age- and BMI matched to pregnant volunteers without diabetes (n = 70) recruited in early pregnancy from maternal health care centres in 2014–2015. Plasma levels of sCD163 and sTWEAK were analysed using commercial ELISA. Plasma levels of sCD163 did not differ between patients with and without GDM in early pregnancy (p = 0.86), plasma levels of sTWEAK however was decreased in women with GDM (0.71 [0.4–1.75] ng/ml) compared to controls (1.38 [0.63–4.86] ng/ml; p = 0.003). Women with sTWEAK levels in the lowest tertile had an increased risk of GDM in early pregnancy (p = 0.014). Neither sCD163 nor sTWEAK were associated with later glucose intolerance in women with GDM. This study reports decreased levels of sTWEAK in women with early pregnancy GDM, independent of age and BMI. Neither sCD163 nor sTWEAK were found to be associated to later glucose intolerance.

Effects of gestational diabetes mellitus on stereological parameters and extravillous trophoblast cells of placenta compared to the control group

The quantitative changes of extravillous trophoblast cells (EVTs) in placenta of gestational diabetes mellitus (GDM) patients were investigated compared to healthy controls using stereological methods. The volumetric parameters of the placenta and EVTs were estimated using Cavalieri’s principle and Physical Disector stereological methods. The placental volume and weight in the GDM group increased compared to the control group (p < .05). The difference in the total volume of intervillous space and blood vessels of the placenta between GDM and control groups was statistically significant (p < .05). In addition, there was a significant difference in the volume density of blood vessels and syncytiotrophoblast between the GDM group and the control group (p < .05). The total volume of the EVTs, nucleus and cytoplasm diameter, volume of the nucleus and cytoplasm, nucleus to cytoplasm ratio (N/C) of EVTs and the total number of EVTs per unit volume of the placenta in the GDM group showed a significant increase compared to the controls (p < .05).Impact statementWhat is already known on this subject? It is reported that extravillous trophoblast cells (EVTs) played an important role in pregnancy complications. There are limited studies on the quantitative changes of EVTs in the placental bed of GDM patients.What do the results of this study add? The results showed that volumetric parameters and number of EVTs were significantly altered in GDM placentas. These changes can be associated with disturbances in trophoblastic invasion in GDM pregnancies and may affect the development and survival of the embryo.What are the implications of these findings for clinical practice and/or further research? In the present study, there is a new insight to placenta structure that probably could be useful to understanding possible mechanisms of pregnancy complications and the achievement of new therapeutic strategies. Further investigation on the molecular biology of these cells in pregnancy complications will be needed to clarify this hypothesis.

Exosome Profiles for Normal and Complicated Pregnancies—A Longitudinal Study [3O

INTRODUCTION: Exosomes are small nanovesicles which play a key role in cell-to-cell communication during pregnancy by transferring bioactive molecules to other cells and modifying their biological functions. Little is known about the changes in the concentration of circulating exosomes throughout gestation in normal and complicated pregnancies. METHODS: A prospective cohort of patients approved by IRB was recruited during pregnancy and retrospectively stratified based on normal (n=30), gestational diabetes mellitus (GDM) (n=10) and preeclampsia (PE) pregnancy outcomes (n=15). Total exosomes and specific placental-derived exosomes (PdE) were determined by Nanoparticle Tracking Analysis using quantum dots coupled with CD63 or PLAP antibodies. Linear mixed modeling was performed on normalized total and PdE across gestation using the lme4 package in R. Using likelihood ratio tests, statistically significant differences were found in exosome concentration across gestation. RESULTS: Significant factors contributing to variations in total and PdE were gestational age and pregnancy outcomes (ANOVA, p&lt;0.05). Post-hoc analyses established that PdE concentrations increased during gestation in normal, GDM and PE pregnancies. The increase was significantly greater in GDM and PE compared with normal pregnancies. Our linear mixed modeling analysis showed that PdE increased ∼2.1-fold in PE and GDM compared to normal through gestation. Interestingly, maternal BMI, glucose concentration and fetal weight significantly affect the concentration of PdE across gestation. CONCLUSION: This study provides evidence of the changes exosomes present in maternal circulation across gestation, suggesting that exosomes may be involved in maternal metabolic adaptation to pregnancy. Further, exosomes can be an early predictor of adverse outcomes, including GDM and PE.

SAT-122 A Mobile App to Decrease Risk Factors for Diabetes in Women with Recent GDM

BACKGROUND: Latinas have one of the highest rates of gestational diabetes mellitus (GDM) in the US. GDM is a major risk factor for type 2 diabetes (T2DM), with up to 60% of women developing T2DM after GDM. Latinos are one of the largest US minority groups, providing impetus for developing lifestyle interventions for this population. The potential to prevent T2DM, including in women with remote GDM, was demonstrated by the Diabetes Prevention Program. However, helping women with recent GDM make behavioral changes needed to decrease risk is a challenge given barriers women with young families face participating in in-person programs. The increasing ubiquity of mobile phone use among Latinos, and rising interest in mobile technologies to deliver healthcare interventions offer the means to overcome these barriers. METHODS: We developed and tested preliminary efficacy of a bilingual (Spanish/English), culturally sensitive, android-based app (¡Hola Bebe, Adios Diabetes!) for promoting healthy lifestyle in obese/overweight Latinas with recent GDM (within 5 years) to reduce risk factors for T2DM in an 8-week trial. Self-efficacy for healthy eating and physical activity (primary outcomes) and weight (secondary outcome) were determined at baseline and study end. The app provided education about health eating and physical activity, action planning, weight tracking, exercise videos, a community forum and motivational text messaging. Achievement in behaviors (e.g., tracking weight) was recognized by badges. RESULTS: We approached 30 women with self-reported Latina ethnicity and recent GDM documented in the medical record within 5 years; 21 provided informed consent and enrolled. Participants were 33 ± 7 (mean±SD) years old and 3 ± 0.7 years from their GDM pregnancy and 14 (64%) reported family history of T2DM. 18 of 21 women (82%) completed the 8-week study providing pre-post data. Self-efficacy for physical activity increased significantly from pre to post (P=.003), self-efficacy for healthy eating increased with borderline significance (P=.059), and weight decreased significantly by 1.5 lbs (P=.003). Backend data revealed a high engagement rate: 91% (19/21) of participants viewed modules/created action plans; 95% (20/21) earned badges by completing a learning module/action plan or weighing. Many posted on the community forum tips for other participants such as a family recipe. Structured interviews with participants revealed that they especially liked the personalized action plans, motivational messages, at-home exercise videos, and recipes. A suggestion for enhancement included adding an “ask the expert” feature to the community forum. CONCLUSION: The ¡Hola Bebe, Adios Diabetes! app was usable and well accepted by Latinas with recent GDM and showed preliminary effectiveness. This program will be tested in a larger, longer randomized trial.*Supported by NIH SBIR grant.

SUN-466 Gestational Diabetes Alters Hypothalamic Development, Microglial Activation, and Insulin Signaling in Offspring

Gestational diabetes mellitus (GDM) is characterized by maternal insulin resistance during pregnancy, leading to high blood glucose levels. Offspring of a GDM pregnancy often have high birth weight that continues through life. GDM influence on developing hypothalamic tanycytes may underlie this outcome. Tanycytes line the third ventricle and project into the median eminence (ME). They are a major component of hypothalamic nutrient sensing, particularly of glucose. Tanycytes are also capable of giving rise to hypothalamic neurons that regulate energy homeostasis and are known to proliferate postnatally in response to diet. We hypothesized that GDM would lead to changes in the tanycyte and ME cell populations of offspring. To study this, we utilized a leptin receptor mutant mouse model, Lepr +/db, that develops GDM during pregnancy. We looked at three potential mechanisms by which GDM could affect the hypothalamus: tanycyte proliferation, insulin signaling, and microglial activation. First, to examine proliferation, we injected wildtype and Lepr +/db dams with BrdU on embryonic days 16.5, 17.5, and 18.5, corresponding with the onset of GDM. Cells immunopositive for BrdU on the day of birth are either minimally proliferating at the time of injection or newly born afterward. We observed significantly fewer positive cells in the α and β1 tanycyte region and in the ME of GDM offspring compared to controls. Fewer cells proliferating in these regions could hinder adaptability to changing metabolic needs. Second, we examined the impact of maternal GDM on insulin signaling in offspring after birth. Brain slices from P9 control and GDM offspring were incubated with vehicle or insulin and immunostained for phospho-AKT (pAKT). While insulin exposure induced pAKT similarly in all offspring, basal pAKT was significantly higher in GDM offspring than controls. pAKT was confined to tanycytes and their projections within the ME. This suggests that GDM offspring have hyperactive insulin signaling when nutrient conditions do not warrant it, particularly in nutrient-sensing tanycytes. Third, we examined microglial activation since GDM causes systemic inflammation in the mothers, and hypothalamic microglia, the brain’s resident immune system, have been shown to play an important role in the development of obesity. We immunostained for Iba-1 in offspring from control and GDM dams on P0 to assess the number and activity state of microglial cells. Compared to offspring of control mothers, offspring born to GDM mothers have more active microglia near α and β1 tanycytes and in the ME. Since microglial activation induced by overnutrition is linked to obesity in adults, a similar mechanism may act on GDM offspring. Taken together, our data suggest that being born to a mother with GDM results in alterations to the tanycyte population and ME, which could play major roles in disordered feeding.

Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.

Abstract P263: Gestational Diabetes and Patterns of Cardiometabolic Risk Factors Before and After Childbearing: Coronary Artery Risk Development in Young Adults Study

Introduction: Cardiometabolic risk factor levels before pregnancy affect risk of gestational diabetes mellitus (GDM), and unfavorable risk factors have been found after pregnancy. However, changes in risk factors during both the pre- and post-childbearing periods have not been evaluated longitudinally in prospective studies. Hypothesis: Women who develop GDM pregnancy exhibit less favorable patterns of CVD risk factors during both pre- and post-childbearing eras. Methods: We used data from CARDIA, a multi-center, longitudinal cohort of black and white young adults initially aged 18-30 with serial in-person exams across 30 years (9 exams, 1985-2016). Women with ≥1 births after baseline (n=1288) self-reported GDM and were classified as “ever” GDM (n=148, at least one GDM pregnancy) and as non-GDM (all non-GDM births; n=1140). Piecewise linear mixed-models, which allowed differing intercepts and slopes for pre- and post-childbearing eras, compared GDM group to non-GDM group on annual changes in CVD risk factor (BMI, waist circumference [WC], lipids, and blood pressure) during pre-childbearing period (before the first post-baseline birth) and post-childbearing period (after the last post-baseline birth). Models adjusted for baseline socioeconomics, length of childbearing period (from the first to the last post-baseline birth), parity, time-varying lifestyle habits and medication use. Results: Annual BMI increase before initiation of childbearing was higher in GDM group than non-GDM group (0.35 vs 0.23 kg/m 2 /year; p=0.03). Similarly, WC showed marked pre-childbearing increase for GDM group compared to non-GDM group (0.82 vs. 0.54 cm/year; p=0.04). In contrast, the annual increase in BMI and WC after childbearing did not differ by GDM history. No differences were detected for the other CVD risk factors. Conclusions: Accelerated gains in overall and central adiposity before the childbearing period was associated with elevated risk of GDM, but risk factor changes do not show differences after childbearing.

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Pregnancy is associated with the onset of many adaptation processes that are likely to change over the course of gestation. Understanding normal metabolites’ variation with pregnancy progression is crucial for gaining insights of the key nutrients for normal fetal growth, and for comparative research of pregnancy-related complications. This work presents liquid chromatography-mass spectrum-based urine metabolomics study of 50 health pregnant women at three time points during pregnancy. The influence of maternal physiological factors, including age, BMI, parity and gravity to urine metabolome was explored. Additionally, urine metabolomics was applied for early prediction of two pregnancy complications, gestational diabetes mellitus and spontaneous abortion. Our results suggested that during normal pregnancy progression, pathways of steroid hormone biosynthesis and tyrosine metabolism were significantly regulated. BMI is a factor that should be considered during cross-section analysis. Application analysis discovered potential biomarkers for GDM in the first trimester with AUC of 0.89, and potential biomarkers for SA in the first trimester with AUC of 0.90. In conclusion, our study indicated that urine metabolome could reflect variations during pregnancy progression, and has potential value for pregnancy complications early prediction. The clinical trial number for this study is NCT03246295.

Micromanaging human placental function: differential microRNA expression in feto-placental endothelial cells of gestational diabetes pregnancies.

Healthy development in utero relies on the appropriate exchange of nutrients and other signalling between the maternal and fetal circulations. Disruption to this fine balance is associated with several pregnancy and adverse birth outcomes, including gestational diabetes mellitus (GDM). This is a complex condition influenced by genetic, environment and potentially epigenetic factors in association with a range of altered developmental outcomes. A recent study, published in Clinical Science, explores miRNAs as a molecular mechanism underpinning the altered function of placental endothelial cells in GDM pregnancies.

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.

Does Gestational Diabetes Cause Additional Risk in Twin Pregnancy?

It has been suggested that the risk of adverse perinatal outcomes in twin pregnancies is exacerbated by concomitant gestational diabetes mellitus (GDM). This study aimed to assess the risk incurred by twin pregnancy and by a diagnosis of GDM, separately, on the development of poor perinatal outcomes. A retrospective cohort study was conducted on all pregnant women at a tertiary center between 2016 and 2017. The impact of GDM and twin pregnancies on perinatal outcomes - birth weight above the 90th centile for gestational age, cesarean delivery, clinical neonatal hypoglycemia, and premature delivery (before 37 weeks' gestation) - was assessed using univariate and multivariate analyses. Overall, 13,527 women were eligible for the study; 11,915 were uncomplicated singleton pregnancies; 1379 of these had GDM; 194 were twin pregnancies, and 39 of these had GDM. Univariate analyses showed that twin pregnancies were associated with a higher risk of all perinatal outcomes except macrosomia. In the multivariate analyses, twin pregnancy was a much higher predictor of cesarean delivery (OR 8.40, 95% CI [6.25, 11.49], p &lt; .0001) and preterm birth (OR 58.82, 95% CI [31.25, 125], p &lt; .0001) compared to GDM but GDM was a higher predictor of neonatal hypoglycemia (OR 4.87, 95% CI [3.74, 6.29], p &lt; .0001). Twin pregnancy is more strongly associated with all adverse perinatal outcomes except macrosomia. GDM does not increase risk of adverse perinatal outcomes except for neonatal hypoglycemia.

The discovery of novel predictive biomarkers and early-stage pathophysiology for the transition from gestational diabetes to type 2 diabetes.

Gestational diabetes mellitus (GDM) affects up to 20% of pregnancies, and almost half of the women affected progress to type 2 diabetes later in life, making GDM the most significant risk factor for the development of future type 2 diabetes. An accurate prediction of future type 2 diabetes risk in the early postpartum period after GDM would allow for timely interventions to prevent or delay type 2 diabetes. In addition, new targets for interventions may be revealed by understanding the underlying pathophysiology of the transition from GDM to type 2 diabetes. The aim of this study is to identify both a predictive signature and early-stage pathophysiology of the transition from GDM to type 2 diabetes. We used a well-characterised prospective cohort of women with a history of GDM pregnancy, all of whom were enrolled at 6-9weeks postpartum (baseline), were confirmed not to have diabetes via 2 h 75 g OGTT and tested anually for type 2 diabetes on an ongoing basis (2years of follow-up). A large-scale targeted lipidomic study was implemented to analyse ~1100 lipid metabolites in baseline plasma samples using a nested pair-matched case-control design, with 55 incident cases matched to 85 non-case control participants. The relationships between the concentrations of baseline plasma lipids and respective follow-up status (either type 2 diabetes or no type 2 diabetes) were employed to discover both a predictive signature and the underlying pathophysiology of the transition from GDM to type 2 diabetes. In addition, the underlying pathophysiology was examined in vivo and in vitro. Machine learning optimisation in a decision tree format revealed a seven-lipid metabolite type 2 diabetes predictive signature with a discriminating power (AUC) of 0.92 (87% sensitivity, 93% specificity and 91% accuracy). The signature was highly robust as it includes 45-fold cross-validation under a high confidence threshold (1.0) and binary output, which together minimise the chance of data overfitting and bias selection. Concurrent analysis of differentially expressed lipid metabolite pathways uncovered the upregulation of α-linolenic/linoleic acid metabolism (false discovery rate [FDR] 0.002) and fatty acid biosynthesis (FDR 0.005) and the downregulation of sphingolipid metabolism (FDR 0.009) as being strongly associated with the risk of developing future type 2 diabetes. Focusing specifically on sphingolipids, the downregulation of sphingolipid metabolism using the pharmacological inhibitors fumonisin B1 (FB1) and myriocin in mouse islets and Min6 K8 cells (a pancreatic beta-cell like cell line) significantly impaired glucose-stimulated insulin secretion but had no significant impact on whole-body glucose homeostasis or insulin sensitivity. We reveal a novel predictive signature and associate reduced sphingolipids with the pathophysiology of transition from GDM to type 2 diabetes. Attenuating sphingolipid metabolism in islets impairs glucose-stimulated insulin secretion.

Metabolic effects of breastfeed in women with prior gestational diabetes mellitus: A systematic review and meta-analysis.

SummaryThis study was undertaken to provide comprehensive analyses of current research developments in the field of breastfeed (BF) and metabolic‐related outcomes among women with prior gestational diabetes mellitus (GDM). Database PubMed, Embase, BIOSIS Previews, Web of Science, and Cochrane Library were searched through December 3, 2017. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were pooled by random‐effects model using Stata version 12.0. Twenty‐three observational studies were included in quantitative synthesis. Reduced possibility of progression to type 2 diabetes mellitus (T2DM; OR = 0.79; 95% CI, 0.68‐0.92) and pre‐DM (OR = 0.66; 95% CI, 0.51‐0.86) were found among women with longer BF of any intensity after GDM pregnancy. The positive effect of longer BF on progression to T2DM gradually became prominent with the extension of follow‐up period. Compared with women with shorter BF, those with longer BF manifested more favourable metabolic parameters, including significant lower body mass index, fasting glucose, triglyceride, and higher insulin sensitivity index. The findings support that BF may play an important role in protection against the development of T2DM‐related outcomes in midlife of women with prior GDM. However, further studies are needed to reveal the etiological mechanism.

490: Consider performing 3-hour GTT when rescreening for GDM in pregnancy

To determine whether women with an elevated early one-hour glucose challenge test (glucola) and a normal 3-hour glucose tolerance test (GTT) should undergo reassessment for gestational diabetes mellitus (GDM) with the glucola screen or the GTT in late second or third trimester. It is recommended that women at higher risk of diabetes be screened early in pregnancy with the glucola test. Those who screen positive (>=130 mg/dL) undergo confirmatory testing with the GTT. Women with normal GTT results are rescreened for GDM later in pregnancy. This is an Institutional Review Board-approved retrospective study of all women who underwent glucola screening at less than 20 weeks (early screening). Of those women who failed the early glucola and passed the early GTT, we assessed whether they had subsequent screening with a glucola or just a repeat GTT in the late second or third trimester (routine screening). The primary outcome was the percentage of women who subsequently failed the glucola test later pregnancy. There were 3040 women who had an early glucola (Figure). Of those, 635 (21%) had a screening value greater than or equal to 130 mg/dL. Of those who failed the early glucola, 490 underwent subsequent GTT, 489 of whom did not meet Carpenter Coustan criteria for diagnosis of GDM. These women were rescreened for GDM in late second or third trimester: 203 underwent glucola and 286 underwent GTT. Married women were more likely to have a late second trimester/third trimester glucola screen rather than GTT. One-hundred and forty-one (69%) of the women who failed the initial glucola (and passed the GTT) again failed the glucola administered later in gestation. Women with an elevated early glucola and normal GTT should be counseled that they have 69% chance of failing the routine glucola screen at 24-28 weeks. They should be given the option of directly performing the glucose tolerance test (at time of routine assessment) in lieu of glucola screen. Otherwise, they may be subject to a delay in diagnosis and two additional oral glucose loads.

Women with gestational diabetes mellitus want clear and practical messages from credible sources about physical activity during pregnancy: a qualitative study.

What are the attitudes of women diagnosed with gestational diabetes mellitus (GDM) towards physical activity during pregnancy? What are the perceived barriers to and enablers of physical activity during pregnancy in women with GDM? A qualitative study with phenomenology and interpretative description as theoretical frameworks. Pregnant women experiencing an uncomplicated singleton pregnancy, diagnosed with GDM, and aged 18 to 40 years were recruited using purposive sampling. Semi-structured interviews were recorded, transcribed verbatim and returned to participants for member checking. Three researchers independently and thematically analysed the qualitative data using an inductive method. Data were coded and compared, and themes were developed, discussed and defined. Recruitment continued until data saturation. Emergent themes were sent to participants and peer reviewed for confirmation. The participants were 27 women, with mean age 32 years (SD 3), mean gestation 30 weeks (SD 5), mean pre-pregnancy body mass index 26 kg/m2 (SD 5), and born in 10 different countries. The process of communicating information about physical activity (messaging) was the main theme to emerge. Sub-themes included: wanting information about physical activity from credible sources; wanting clear, specific information about safe physical activity during a GDM pregnancy; receiving information at GDM diagnosis because this event triggered women's desire to be more physically active; understanding why physical activity is important to improving outcomes for themselves and their babies; and wanting information about flexible, convenient and practical physical activity options. To feel confident and safe about being physically active during pregnancy, women with GDM wanted clear, simple and GDM-specific messages from credible sources. Health professionals can support women with a GDM pregnancy with targeted physical activity messages.

Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes.

Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher’s least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children.

MEG3 damages fetal endothelial function induced by gestational diabetes mellitus via AKT pathway.

To explore the role of maternally-expressed gene 3 (MEG3) in fetal endothelial dysfunction induced by gestational diabetes mellitus (GDM) and its underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were extracted from GDM pregnancies and normal pregnancies. Cell proliferation, apoptosis, migration and angiogenesis of HUVECs were detected by cell counting kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), wound healing and tube formation assay, respectively. MEG3 expressions in HUVECs extracted from 16 GDM pregnancies and 18 normal pregnancies were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Besides, angiogenesis and MEG3 expression in HUVECs treated with glucose were detected, respectively. Proliferation, apoptosis, migration and angiogenesis were also detected after HUVECs were transfected with MEG3 lentivirus. Target genes of MEG3 were predicted by bioinformatics method and further verified by luciferase reporter gene assay. The protein expression of possible signaling pathway was detected by Western blot. HUVEC cells extracted from GDM pregnancies presented increased apoptosis and decreased proliferation, migration and angiogenesis compared with those from healthy pregnancies. Meanwhile, MEG3 was overexpressed in HUVECs extracted from GDM pregnancies compared with that of healthy pregnancies. High dose of glucose treatment led to reduced angiogenesis and elevated MEG3 expression in HUVECs. MEG3 overexpression further promoted apoptosis, but inhibited proliferation, migration and angiogenesis of HUVECs. By bioinformatics and luciferase reporter gene assay, microRNA-370-3p was found to be the target gene of MEG3 and directly targeted on AFF1. Moreover, MEG3 overexpression led to downregulated microRNA-370-3p and upregulated AFF1 mainly through inhibiting PI3K/AKT pathway. MEG3 is overexpressed in HUVECs extracted from GDM pregnancies. MEG3 damages fetal endothelial function through targeting microRNA-370-3p and AFF1 via PI3K/AKT pathway.

Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity

There is increasing evidence that miRNAs, which are enriched in nanovesicles called exosomes, are important regulators of gene expression. When compared with normal pregnancies, pregnancies with gestational diabetes mellitus (GDM) are associated with skeletal muscle insulin resistance as well as increased levels of circulating placental exosomes. Here we investigated whether placental exosomes in GDM carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villous (CV) explants from both women with Normal Glucose Tolerant (NGT) and GDM pregnancies. Using miRNA sequencing, we identified a specific set of miRNAs selectively enriched with exosomes and compared with their cells of origin indicating a specific packaging of miRNAs into exosomes. Gene target and ontology analysis of miRNA differentially expressed in exosomes secreted in GDM compared with NGT are associated with pathways regulating cell migration and carbohydrate metabolism. We determined the expression of a selected set of miRNAs in placenta, plasma, and skeletal muscle biopsies from NGT and GDM. Interestingly, the expression of these miRNAs varied in a consistent pattern in the placenta, in circulating exosomes, and in skeletal muscle in GDM. Placental exosomes from GDM pregnancies decreased insulin-stimulated migration and glucose uptake in primary skeletal muscle cells obtained from patients with normal insulin sensitivity. Interestingly, placental exosomes from NGT increase migration and glucose uptake in response to insulin in skeletal muscle from diabetic subjects. These findings suggest that placental exosomes might have a role in the changes on insulin sensitivity in normal and GDM pregnancies.

Programming of Vascular Dysfunction in the Intrauterine Milieu of Diabetic Pregnancies.

With the rising global tide of obesity, gestational diabetes mellitus (GDM) burgeoned into one of the most common antenatal disorders worldwide. Macrosomic babies born to diabetic mothers are more likely to develop risk factors for cardiovascular disease (CVD) before they reach adulthood. Rodent studies in offspring born to hyperglycemic pregnancies show vascular dysfunction characterized by impaired nitric oxide (NO)-mediated vasodilation and increased production of contractile prostanoids by cyclooxygenase 2 (COX-2). Vascular dysfunction is a key pathogenic event in the progression of diabetes-related vascular disease, primarily attributable to glucotoxicity. Therefore, glucose-induced vascular injury may stem directly from the hyperglycemic intrauterine environment of GDM pregnancy, as evinced by studies showing endothelial activation and inflammation at birth or in childhood in offspring born to GDM mothers. This review discusses potential mechanisms by which intrauterine hyperglycemia programs dysfunction in the developing vasculature.