Gestational Diabetes Mellitus Pregnancies Research Articles

Establishment of pregnancy-specific lipid reference intervals in pregnant women in a single-centre and assessment of the predictive value of early lipids for gestational diabetes mellitus: a prospective cohort study.

This study was aimed at establishing a pregnancy-specific lipid reference interval (RI) in pregnant women in a single-centre in the Beijing area of China, simultaneously exploring the predictive value of lipid levels in early pregnancy for gestational diabetes mellitus (GDM). From October 2017 to August 2019, Peking University International Hospital established records for 1588 pregnant women, whose lipid profiles were determined during the first and third trimesters. The Hoffmann technique was used to calculate gestation-specific lipid RI. The 95% reference range for gestational lipids was also estimated for 509 healthy pregnant women screened according to the Clinical and Laboratory Standards Institute guideline. Multivariate logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence interval (CI), and the receiver operating characteristic (ROC) curve was applied to assess the predictive value of lipids in the first trimester for the diagnosis of GDM. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the third trimester (p < 0.05). Hoffmann technique RI of the lipid profiles and the 95% reference range of the lipid profiles in healthy pregnant women did not differ statistically (p > 0.05). TC, TG, and LDL-C levels were higher in the GDM group in the first trimester (p < 0.05), and the risk of GDM was 2.1 times higher in women with higher TG (95% CI: 1.13-3.77, p < 0.05). The optimal ROC cut-off for TG to predict GDM was 2.375 mmol / L, and the area under the ROC curve was 0.622 (95% CI: 0.592-0.751), with a sensitivity of 73.7% and a specificity of 59.3%. This study established pregnancy-specific lipid RI for pregnant women in a single centre in the Beijing area of China. Pregnant women with TG ≥ 2.375 mmol/L in the first trimester were at significantly increased risk for GDM.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

Women with Gestational Diabetes Mellitus do not have compromised polyunsaturated fatty acid status

Pregnant women who develop pre-eclampsia (PE) and/or intra-uterine growth restriction (IUGR) have reduced polyunsaturated fatty acid (PUFA) status compared to healthy pregnancy(1). It is unknown if pregnant women diagnosed with Gestational Diabetes Mellitus (GDM), and their offspring, also have compromised PUFA status. To determine if women with GDM, and their offspring, have altered PUFA status compared to healthy pregnancy. Pregnant women were recruited from Glasgow Scotland, and Brisbane, Australia from antenatal clinics for this cross sectional study. Third trimester maternal blood samples were collected after an overnight fast and cord blood samples were collected at delivery. Plasma fatty acids were analysed using gas chromatography from women with GDM (n = 37) and healthy pregnancies (n = 27) and their respective offspring (n = 31, from women with GDM, and n = 27 from healthy women). T-tests were used to determine significant differences between maternal with GDM and healthy pregnancy, as well as for their offspring and significance was set at p&lt;0.05. Previously, erythrocyte fatty acids were analysed from women with PE (n = 21), IUGR (n = 13) and healthy pregnancies (n = 86)(1). All results were expressed as mol percent of total fatty acids. There were no differences in maternal plasma arachidonic acid (4.51 ± 1.23 vs. 4.72 ± 0.64, p = 0.39) and plasma EPA &amp; DHA (2.33 ± 0.74 vs 2.69 ± 1.04, p = 0.14) in women with GDM and healthy pregnancies, respectively. There were no differences in fetal plasma arachidonic acid (11.58 ± 2.26 vs. 12.63 ± 1.69, p = 0.08) and plasma EPA &amp; DHA (4.44 ± 1.17 vs. 4.44 ± 1.00, p = 0.89) in offspring from women with GDM and healthy pregnancies, respectively. Women with PE and IUGR had approximately 25% lower erythrocyte EPA &amp; DHA and 35% lower erythrocyte arachidonic acid compared to healthy pregnant(1). Offspring from women with PE and IUGR had approximately 25% lower erythrocyte EPA &amp; DHA and 22% lower erythrocyte arachidonic acid compared to healthy pregnancy(1).Women with PE and IUGR had lower PUFA status likely due to reduced PUFA synthesis(1) and offspring from women with PE and IUGR had reduced PUFA status likely due to ectopic fat in placenta tissue(2). Women with GDM do not have compromised PUFA status suggesting there is no reduced synthesis and transport of PUFA. Offspring from women with GDM do not have reduced PUFA status suggesting there is no problem with PUFA transport across the placenta, unlike offspring from women with PE and/or IUGR. Women with GDM, and their offspring, do not have compromised plasma PUFA status compared to healthy pregnancy.

Comparisons of the Rates of Large-for-Gestational-Age Newborns between Women with Diet-Controlled Gestational Diabetes Mellitus and Those with Non-Gestational Diabetes Mellitus.

(1) Objectives: The primary objective is to compare the rate of large-for-gestational-age (LGA) between women with diet-controlled gestational diabetes mellitus (GDM) and those with non-GDM, and to assess whether or not diet-controlled GDM is an independent factor of LGA fetuses. The secondary objectives are to compare the rates of other common adverse pregnancy outcomes, such as preeclampsia, cesarean section rate, preterm birth, and low Apgar score, between pregnancies with diet-controlled GDM and non-GDM pregnancies. (2) Methods: A retrospective cohort study was conducted on singleton pregnancies, diagnosed with GDM and non-GDM between 24 and 28 weeks of gestation, based on a two-step screening test. The prospective database of the obstetric department was accessed to retrieve the records meeting the inclusion criteria, and full medical records were comprehensively reviewed. The patients were categorized into two groups, GDM (study group) and non-GDM (control group). The main outcome was the rate of LGA newborns, and the secondary outcomes included pregnancy-induced hypertension, preterm birth, cesarean rate, low Apgar scores, etc. (3) Results: Of 1364 recruited women, 1342 met the inclusion criteria, including 1177 cases in the non-GDM group and 165 (12.3%) in the GDM group. Maternal age and pre-pregnancy BMI were significantly higher in the GDM group. The rates of LGA newborns, PIH, and cesarean section were significantly higher in the GDM group (15.1% vs. 7.1%, p-value < 0.001; 7.8% vs. 2.6%, p-value = 0.004; and 54.5% vs. 41.5%, p-value = 0.002; respectively). On logistic regression analysis, GDM was not significantly associated with LGA (odds ratio 1.64, 95% CI: 0.97-2.77), while BMI and gender were still significantly associated with LGA. Likewise, GDM was not significantly associated with the rate of PIH (odds ratio: 1.7, 95% CI: 0.825-3.504), while BMI and maternal age were significantly associated with PIH, after controlling confounding factors. (4) Conclusions: The rates of LGA newborns, PIH, and cesarean section are significantly higher in women with diet-controlled GDM than those with non-GDM. Nevertheless, the rates of LGA newborns and PIH are not directly caused by GDM but mainly caused high pre-pregnancy BMI and advanced maternal age, which are more commonly encountered among women with GDM.

Use of the Japanese gestational diabetes mellitus diagnostic strategy during the COVID‐19 pandemic in Japan: A questionnaire survey

AbstractAimSome concerns exist that diagnosis of gestational diabetes mellitus (GDM) may be missed when the simplified diagnostic criteria of the Japanese Society of Diabetes and Pregnancy (JSDP) for GDM (published during the COVID‐19 pandemic) are used. Moreover, limited data is available regarding how widespread these diagnostic criteria are used when managing GDM during the COVID‐19 pandemic. Therefore, this study aimed to determine how GDM diagnosis has changed during the COVID‐19 pandemic in Japan.MethodsThe changes in GDM diagnosis during the COVID‐19 pandemic were investigated using an online questionnaire to 2159 obstetric facilities in Japan. The questionnaire collected data on facility type, awareness of Japanese GDM diagnostic strategies, modifications to diagnostic methods for early and late GDM, and opinions on GDM management, with the pandemic divided into seven periods.ResultsWe received responses from 593 facilities (27%). Approximately 90% of the facilities did not change their diagnostic process for early GDM or late GDM (occurring after 24 weeks gestation). However, during the COVID‐19 pandemic, 19 facilities discontinued the use of 75‐g oral glucose tolerance tests before 24 weeks of gestation, and 17 facilities discontinued it after 24 weeks of gestation, instead using the aforementioned Japanese GDM diagnostic strategy.ConclusionsAlthough a limited number of facilities modified their diagnostic method in response to the COVID‐19 pandemic, this study demonstrated that those that adjusted their diagnostic method primarily used the Japanese COVID‐19 GDM strategy by the JSDP.

Role of Ductus Venosus Doppler Sonography for the Prediction of Perinatal Outcome in Term Pregnancies Complicated by Gestational Diabetes Mellitus.

Ductus venosus (DV) Doppler velocimetry reflects fetal cardiac function. Gestational diabetes mellitus (GDM) is assumed to impair cardiac function due to fetal hyperglycemia. The purpose of this study was to assess the ability of DV Doppler to predict an adverse perinatal outcome (APO) in term pregnancies with GDM. This is a retrospective cohort study including GDM pregnancies of singleton, non-anomalous fetuses without any signs of placental dysfunction. All GDM women who primarily had a vaginal delivery attempt and in which DV Doppler was examined from 37+0 weeks on were included. Receiver operating characteristic curve (ROC) analyses were performed to assess the predictive value of DV pulsatility index (DV-PI) regarding a composite APO (CAPO). Furthermore, a subgroup analysis was performed regarding the presence of a large-for-gestational-age (LGA) newborn. A total of n=89 cases were included. Overall, CAPO occurred in 26 out of 89 cases (29.2%). All DV Doppler examinations showed a positive A wave. DV-PI was>95th percentile in 8 out of 89 cases (9%). Overall, ROC analysis showed no significant association of DV-PI with CAPO (AUC=0.523, p=0.735). However, regarding individual APO parameters, ROC analysis showed a significant association of DV-PI with 5th-min AGPAR (AUC=0.960, p=0.027), which was not confirmed after exclusion of LGA cases. In GDM pregnancies at term, DV Doppler sonography seems to have no benefit for APO prediction.

Time to Move Beyond a Binary Criterion for Gestational Diabetes?

Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM.

Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus.

Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case-control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal-fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38-40 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs' protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.

Effects of mHealth-Based Lifestyle Interventions on Gestational Diabetes Mellitus in Pregnant Women With Overweight and Obesity: Systematic Review and Meta-Analysis.

The increasing incidence of gestational diabetes mellitus (GDM) is a global health problem that is more likely to occur in pregnant women with overweight or obesity. Adhering to a healthy lifestyle is associated with a reduced risk of GDM. With the development of IT, mobile health (mHealth) interventions have become widely available in health care. However, there are no definitive conclusions on the effectiveness of mHealth-based lifestyle interventions in preventing GDM. This study aims to evaluate the impact of mHealth-based lifestyle interventions on GDM and other pregnancy outcomes in pregnant women with overweight or obesity. A systematic literature search was conducted in 5 English databases (MEDLINE, Embase, Web of Science, CENTRAL, and CINAHL) and 4 Chinese databases (CBM, CNKI, Vip, and Wanfang) to identify randomized controlled trials (RCTs) on the effectiveness of mHealth-based interventions for GDM from inception to January 10, 2023. In total, 2 authors independently screened the studies and extracted the data. The quality of the included studies was examined using the Cochrane risk-of-bias tool. Data synthesis was conducted using Review Manager (version 5.4; The Cochrane Collaboration). A total of 16 RCTs with 7351 participants were included in this study. The included studies were published between 2014 and 2021 and were conducted in China, the United States, Australia, New Zealand, the United Kingdom, Ireland, and Norway. The sample sizes of the studies ranged from 75 to 2202, and the duration of the mHealth-based lifestyle interventions ranged from 4 to 28 weeks. Compared with usual care, mHealth-based lifestyle interventions significantly reduced the incidence of GDM (odds ratio [OR] 0.74, 95% CI 0.56-0.96; P=.03; I2=65%), preterm birth (OR 0.65, 95% CI 0.48-0.87; P=.004; I2=25%), macrosomia (OR 0.59, 95% CI 0.40-0.87; P=.008; I2=59%), and gestational weight gain (mean difference=-1.12 kg, 95% CI -1.44 to -0.80; P<.001; I2=43%). The subgroup analysis showed that interventions delivered via apps (OR 0.55, 95% CI 0.37-0.83; P=.004; I2=44%), provided by obstetricians (OR 0.69, 95% CI 0.51-0.93; P=.02; I2=60%), and targeted at Asian populations (OR 0.44, 95% CI 0.34-0.58; P<.001; I2=0%) and that used the International Association of Diabetes and Pregnancy Study Groups diagnostic criteria (OR 0.58, 95% CI 0.39-0.86; P=.007; I2=69%) showed a statistically significant reduction in the risk of GDM. mHealth-based lifestyle interventions had a favorable impact on the prevention of GDM in pregnant women with overweight and obesity. Future studies need to further explore the potential of mHealth-based interventions for GDM through better design and more rigorous large-scale RCTs. PROSPERO International Prospective Register of Systematic Reviews CRD42021286995; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=286995.

Gestational diabetes mellitus in patients undergoing assisted reproductive techniques or conceiving spontaneously: an analysis on maternal and foetal outcomes.

With the rise of medically assisted reproductive techniques (ART) the number of pregnanciescomplicated by gestational diabetes mellitus (GDM) has increased. The aim of this study was to evaluateretrospectively the outcomes of pregnancies complicated by GDM who conceive trough ART (cases) compared tothose who conceived spontaneously (controls). In 670 women with GDM, 229 cases and 441 controls, followed by the Diabetology of Padua, between2010-2022, clinical-metabolic maternal characteristics and maternal-foetal outcomes were evaluated. As for the maternal clinical-metabolic characteristics, plasma glucose levels at 60' and 120' under oralglucose tolerance test (OGTT) at time of diagnosis were significantly higher in cases (177.4 ± 31.1 vs 170.9 ± 34.1 mg/dl, p = 0.016; 151.5 ± 32.2 vs 144.0 ± 33.4 mg/dl, p = 0.005 respectively). Furthermore, at diagnosis, cases showhigher levels of total cholesterol (257 ± 53 mg/dl vs 246 ± 52 mg/dl; p = 0.012) and triglycerides (199.8 ± 83.2 mg/dl vs 184.9 ± 71.3 mg/dl; p = 0.02) compared to controls. As for maternal outcomes, thyroid disfunction, was recorded in ahigher percentage in case (21.4% vs 14.3%; p = 0.008), as well as, the frequency of cesarean section (50.3% vs41.2%; p = 0.038) and twin pregnancies (16.2% vs 2.5%; p < 0.001). As for neonatal outcomes, there were nostatistically significant differences, except for the birth weight of the second twin, which was significantly lower incases (2268 ± 536 vs 2822 ± 297 g; p = 0.002). No other significant differences were found. This study showed no meaningful differences in the outcomes of GDM pregnancies who were conceived with ART compared to that arose spontaneously as the patients were promptly diagnosed and treated.

Association of MST1 in the First Trimester of Pregnancy with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

We investigate the association of mammalian sterile line 20-like kinase 1 (MST1) in the first trimester with the risks of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Pregnancies were recruited during their first antenatal care visit between 8 and 12 gestational weeks. These pregnancies underwent an oral glucose tolerance test between 24 and 28 gestational weeks and were followed up until delivery. Serum MST1 levels at 8-12 gestational weeks and 24-28 gestational weeks were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Logistic regression models were used to evaluate the association between MST1 levels in the first trimester and the risks of GDM and adverse pregnancy outcomes. This cohort study enrolled a total of 231 pregnancies. GDM was present in 42 (18.18%) women. Compared to the normal glucose tolerance (NGT) group, the GDM group had higher levels of FPG, HOMA-IR, and MST1 both in the first and second trimesters, but had lower HOMA-β levels only in the second trimester. Then participants were classified according to the median MST1 value in the first trimester. Incidences of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia increased in women with higher MST1 values. Serum MST1 in the first trimester was correlated with FPG, 1hr PG, 2hr PG, and HOMA-IR, while inversely correlated with HOMA-β in the second trimester. Furthermore, after adjusting for traditional risk factors, women with higher first-trimester MST1 values had greater odds of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia (aOR 2.276, P=0.030; aOR 2.690, P=0.003; aOR 3.210, P=0.048; aOR 5.488, P=0.010). Elevated levels of MST1 in the first trimester of pregnancies are associated with increased risks of GDM and adverse pregnancy outcomes.

Differential response of placental cells to high D‐glucose and its impact on extracellular vesicle biogenesis and trafficking via small GTPase Ras‐related protein RAB‐7A

AbstractPlacental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5‐mM D‐glucose (i.e. control) or 25‐mM D‐glucose (high glucose). Cell‐conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K‐g, pellet 10K‐g, and pellet 100K‐g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRMHR) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, n = 6) and those with GDM (n = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies.

Maternal Serum Copper and Some Metabolic Indexes in Late Second Trimester of Gestational Diabetes Mellitus Pregnancy.

Copper (Cu) is a physiologically important trace element during pregnancy. The study aim is to assess the altered level of serum Cu and its association with some metabolic indexes in Gestational Diabetes Mellitus (GDM). A total of 108 pregnant women (aged 18 - 40, second trimester) are included in the study and divided into two groups (GDM n = 54; pregnant with normal glucose tolerance (NGT), n = 54) after performing a 2-hour 75-g oral glucose tolerance test (OGTT). Maternal blood samples are collected at 26 - 28 gestational week. All biochemical parameters are measured in serum from fasting venous blood. Serum Cu levels are analyzed by flame atomic absorption spectrophotometry (Perkin Elmer AAnalyst 300, USA). Body Mass Index (BMI), insulin sensitivity/resistance, triglyceride-glucose (TyG), TyG-BMI (triglyceride glucose-body mass) indexes are calculated by formulas. The following data were observed: significantly higher levels of serum Cu (p = 0.009), pre-pregnancy BMI (pre-pBMI), BMI at the GDM diagnosis (pBMI), TyG, pregnancy TyG-BMI (pTyG-BMI) p < 0.001, and triglycerides (Tgl) (p = 0.02) in GDM compared to NGT pregnancy. The study presents a positive correlation between serum Cu and pre-pBMI (p < 0.02), pBMI and pTyG-BMI (p < 0.001). Besides, pre-pBMI (mean ≥ 25 kg/m2), pBMI (mean ≥ 30 kg/m2), and pTyG-BMI are associated with 14.5% (OR 1.145, 95% CI: 1.064 - 1.232; p < 0.001), 15.3% (OR 1.153, 95% CI: 1.070 - 1.243; p < 0.001), and 5.9% (OR 1.059, 95% CI: 1.022 - 1.086; p < 0.001) increased risk for GDM development. No association is found between Cu and Tgl levels, fasting plasma glucose e(FPG) and TyG. ROC analysis suggests the serum Cu as a possible risk factor for GDM development. The analysis shows that at a cutoff point of ≥ 31.9 µmol/L, serum Cu presents a sensitivity and specificity of 64.8% and 66.7% in the prediction of GDM development (AUC = 0.659, p < 0.012). After adjustment for maternal age, gestational age, and family predisposition, the odds ratios (ORs) (95% CIs) still show association of Cu levels with increased GDM risk (OR 1.099, 95% CI 1.018 - 1.184, p = 0.013). pTyG-BMI index exhibits a better interaction than TyG index, Tgl, and glucose separately with serum Cu levels where BMI has a mediator's role.

Variation in clinical practice guideline recommendations for medication use in pregnancy in Australia: A systematic review

AbstractBackgroundMedication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent.AimsThis systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM).Materials and MethodsA literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.ResultsWe identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first‐line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed.ConclusionMultiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.

Kidney Disease in Women With Previous Gestational Diabetes Mellitus: A Nationwide Register-Based Cohort Study.

The association between gestational diabetes mellitus (GDM) and incident kidney disease, the mediating effects of diabetes and hypertension, and the impact of severity of metabolic dysfunction during pregnancy on the risk of incident kidney disease were investigated in this study. This Danish, nationwide, register-based cohort study included all women giving birth between 1997 and 2018. Outcomes included chronic kidney disease (CKD) and acute kidney disease, based on diagnosis codes. Cox regression analyses explored the association between GDM and kidney disease. A proxy for severity of metabolic dysfunction during pregnancy was based on GDM diagnosis and insulin treatment during GDM in pregnancy and was included in the models as an interaction term. The mediating effects of subsequent diabetes and hypertension prior to kidney disease were quantified using mediation analyses. Data from 697,622 women were used. Median follow-up was 11.9 years. GDM was associated with higher risk of CKD (adjusted hazard ratio [aHR] 1.92; 95% CI 1.67-2.21), whereas acute kidney disease was unrelated to GDM. The proportions of indirect effects of diabetes and hypertension on the association between GDM and CKD were 75.7% (95% CI 61.8-89.6) and 30.3% (95% CI 25.2-35.4), respectively, as assessed by mediation analyses. The CKD risk was significantly increased in women with insulin-treated GDM and no subsequent diabetes compared with women without GDM (aHR 2.35; 95% CI 1.39-3.97). The risk of CKD was significantly elevated after GDM irrespective of subsequent development of diabetes and hypertension. Furthermore, women with severe metabolic dysfunction during pregnancy had the highest CKD risk.

Glycemic Variability and Its Correlation with Large for Gestation-age Babies in Gestational Diabetic Pregnancies.

Although glycemic variability (GV) has been shown to be associated with endothelial dysfunction in diabetes mellitus (DM), there is a dearth of literature on its correlation in gestational diabetic pregnancies. To compare GV and 24-hour ambulatory glucose profile (AGP) in gestational diabetic pregnancies with and without large for gestation-age (LGA) babies. It was a cross-sectional observational study. A total of 40 pregnant females between 19 and 35 years with gestational DM (GDM) controlled on pharmacotherapy fulfilling inclusion criteria were recruited. A flash glucose monitor (FGM) was used to record AGP between 32 and 36 weeks of gestation in these women. A total of 400 patient days with 38,400 glucose values in the study group were analyzed. Various glucose measures were compared between the GDM pregnancies with or without LGA babies. The incidence of LGA was 15% in these pregnant women who were on pharmacotherapy and apparently controlled as evidenced by self-monitoring of blood sugar values. All the parameters of 24-hour AGP except dinner values were significantly high in the LGA group when compared with the non-LGA group [mean amplitude of glycemic excursion (MAGE) LGA vs non-LGA 74.58 ± 16.83 vs 49.86 ± 12.83 mg/dL, p = 0.002; standard deviation (SD) LGA vs non-LGA 30.19 ± 9.69 vs 20.10 ± 5.97 mg/dL, p = 0.001]. Variables of GV: MAGE and SD were significantly high in the LGA group (p < 0.001). Time below range (TBR) and time above range (TAR) were also significantly altered in the LGA group (p < 0.001). High GV and time in the range are the important parameters that can be well correlated with LGA babies in gestational diabetic pregnancies on pharmacotherapy. An FGM is a good monitoring device to measure this parameter and can be used as an adjunct to modify measures to control the glucose values within range in these pregnancies.

L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus

BackgroundMaternal hyperglycaemia has a significant impact on placental metabolism and mitochondrial function. The NLRP3 inflammasome is responsive to endogenous signals of mitochondrial dysfunction. We tested our hypothesis that mitochondrial dysfunction orchestrates activation of the NLRP3 inflammasome and contributes to inflammation in gestational diabetes mellitus (GDM). MethodsFasting blood, omental and placental tissue were collected on the day of caesarean section from nulliparous women with normal glucose tolerant (NGT) (n = 30) and GDM (n = 27) pregnancies. Cell-free mitochondrial DNA (cf-mtDNA) copy number was quantified by real-time PCR. M1-like (CD14+CD86+CD206-) and M2-like (CD14+CD86+CD206+) macrophage populations were characterized by flow cytometry. Immunoblotting for protein expression of NLRP3, ASC and caspase-1 was performed in maternal BMI and age-matched tissue samples. IL-1β and IL-18 were measured by multiplex ELISA. Placental explants from GDM participants were cultured for 24 h with 1 mM L-ergothioneine (antioxidant) and 1 µM MCC950 (NLRP3 inhibitor). ResultsCf-mtDNA copy numbers were significantly higher in GDM compared to NGT participants (p = 0.002). Placental populations of CD14+ (p = 0.02) and CD14+CD86+CD206- (p = 0.03) macrophages produced significantly increased levels of mitochondrial superoxide in GDM compared to NGT participants. Placental production of IL-18 (p = 0.04) was significantly increased in GDM. This increase in placental IL-18 was attenuated by treatment with 1 µM MCC950 (p = 0.0005), and 1 mM L-ergothioneine (p = 0.007). ConclusionPlacental inflammation is significantly increased in women with GDM. Furthermore, this increase may be initiated by elevated production of mitochondrial superoxide by macrophage subpopulations and orchestrated by the NLRP3 inflammasome. The mitochondrial antioxidant, L-ergothioneine, ameliorates NLRP3-induced placental inflammation in GDM, identifying a potential therapeutic role.

Prevalence and treatment of gestational diabetes in Norway 2010–2020

AimsEstimate prevalence of gestational diabetes mellitus (GDM) and its treatment in Norway 2010–2020 and explore impact of new national GDM guidelines in 2017. MethodsWe identified women giving birth in a nationwide cohort study using registers on births, prescriptions, education, primary and specialist care. For each year, we estimated prevalence of GDM overall, by BMI, age, education, and mother’s birthplace; proportions of GDM pregnancies receiving pharmacological treatment; and distribution of the gestational week when GDM was diagnosed. ResultsIn 633,169 pregnancies, prevalence of GDM increased from 2.6 % in 2010 to 6.0 % in 2016, then stabilized. Similar patterns were seen across strata of BMI, age, education, and maternal birthplace, although prevalence was higher with higher BMI, higher age, lower education, and mothers born in Asia, Africa, or Middle East. The proportion of the GDM population pharmacologically treated increased from 11.6 % in 2010 to 13.6 % in 2016 and 31.6 % in 2020. GDM was diagnosed in recommended gestational week 24–28 in 19 % versus 45 % of GDM pregnancies in 2010 and 2020, respectively. ConclusionsBoth the proportion diagnosed with GDM within recommended time of screening, and who received pharmacological treatment, increased substantially following new guidelines in 2017. Prevalence of GDM increased from 2010 to 2016, then plateaued.

Uterine Arteries Resistance in Pregnant Women with Gestational Diabetes Mellitus, Diabetes Mellitus Type 1, Diabetes Mellitus Type 2, and Uncomplicated Pregnancies.

The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries' pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. This was a retrospective case-control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups.

Gestational diabetes mellitus in pregnancies conceived after infertility treatment: a population-based study in the United States, 2015–2020

To evaluate the risk of gestational diabetes mellitus (GDM) in singleton pregnancies conceived using infertility treatment and examine the influence of race and ethnicity as well as prepregnancy body mass index (BMI). Cross-sectional study using the US vital records data of women that delivered singleton births. United States, 2015-2020. Any infertility treatment was divided into two groups: those that used fertility-enhancing drugs, artificial insemination, or intrauterine insemination, and those that used assisted reproductive technology (ART). Gestational diabetes mellitus, defined as a diagnosis of diabetes mellitus during pregnancy, includes both diet-controlled GDM and medication-controlled GDM in singleton pregnancies conceived with infertility treatment or spontaneously and delivered between 20- and 44-weeks' gestation. We also examined whether the infertility treatment-GDM association was modified by maternal race and ethnicity as well as prepregnancy BMI. Associations were expressed as a rate ratio (RR) and 95% confidence interval (CI), derived from log-linear models after adjustment for potential confounders. A total of 21,943,384 singleton births were included, with 1.5% (n = 318,086) undergoing infertility treatment. Rates of GDM among women undergoing infertility treatment and those who conceived spontaneously were 11.0% (n = 34,946) and 6.5% (n = 1,398,613), respectively (adjusted RR 1.24, 95% CI 1.23, 1.26). The RRs were adjusted for maternal age, parity, education, race and ethnicity, smoking, BMI, chronic hypertension, and year of delivery. The risk of GDM was modestly increased for those using fertility-enhancing drugs (adjusted RR 1.28, 95% CI 1.27, 1.30) compared with ART (adjusted RR 1.18, 95% CI 1.17, 1.20), and this risk was especially apparent for non-Hispanic White women (adjusted RR 1.29, 95% CI 1.26, 1.31) and Hispanic women (adjusted RR 1.35, 95% CI 1.29, 1.41). The number of women who needed to be exposed to infertility treatment to diagnose one case of GDM was 46. Prepregnancy BMI did not modify the infertility treatment-GDM association overall and within strata of race and ethnicity. These general patterns were stronger after potential corrections for misclassification of infertility treatment and unmeasured confounding. Infertility treatment, among those who received fertility-enhancing drugs, is associated with an increased GDM risk. The persistently higher risk of GDM among women who seek infertility treatment, irrespective of prepregnancy weight classification, deserves attention. Infertility specialists must be vigilant with preconception counseling and ensure that all patients, regardless ofrace and ethnicity or BMI, are adequately tested for GDM early in pregnancy using a fasting blood glucose level or a traditional 50-g oral glucose tolerance test. Testing may be completed by the infertility specialist or deferred to the primary prenatal care provider at the first prenatal visit.