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The primary objective of this study was to examine the effect of gestational diabetes mellitus (GDM) on pelvic girdle pain (PGP) occurrence and symptom severity. Pregnant women who were with/without GDM, 20-40 years of age, and also in the second and third trimesters of pregnancy were included in the study. PGP provocation tests were administered to 187 pregnant women to determine the presence and severity of PGP. Based on the test results, the study subjects were divided into two groups; Group 1 (GDM+, PGP+; n:32) and Group 2 (GDM-, PGP+; n:35). Both groups were asked to fill in the Pelvic Girdle Questionnaire (PGQ). The relationship between the presence of GDM and the presence of PGP was found to be significant (p = .043). It was found the groups were similar in view of pain, and also in PGQ total/subscale scores (p > .05). Although GDM has no effect on symptom severity, it has been determined that it may relate to the development of PGP. Therefore, early interventions (nutrition, exercise, belt using, etc.) are recommended to prevent the development of PGP in pregnant women with a family history of diabetes, with a previous diagnosis of diabetes and/or with GDM detected in their previous pregnancies. What is already known on this subject? Gestational diabetes mellitus and pelvic girdle pain are pathologies that develops secondary to pregnancy-related systemic and biomechanical changes. What do results on this study add? GDM may related the development of PGP. What are the implications of these findings for clinical practice and/or further research? Early interventions (nutrition, exercise, belt using, etc.) and strict control of pregnant women in view of PGP is recommended to prevent the development of PGP in pregnant women with a family history of diabetes, with previous diagnosis of diabetes and/or with GDM detected in their previous pregnancies. The evaluation of pregnant women for PGP before administering interventions, such as exercise and diet (both decrease the pro-inflammatory markers), following the diagnosis of GDM and the measurement of plasma anti- and pro-inflammatory marker values in the same time period will further reveal the relationship between GDM and PGP.

U Klinici za ženske bolesti i porode KBC-a Zagreb provedeno je prospektivno istraživanje u razdoblju od 2009. godine do 2014. godine s 251 ispitanicom s GDMom u anamnezi te njihovom djecom. Cilj istraživanja bio je utvrditi učestalost poremećaja glikemije, lipida, metaboličkog sindroma te naći rane biljege bolesti. Ispitanice su podijeljene u četiri skupine s obzirom na vrijeme proteklo od porođaja do kontrolnog pregleda, prva šest mjeseci, druga godinu dana, treća dvije i četvrta pet godina poslije porođaja. Uz antropometrijske mjere izmjerene su koncentracije C-peptida, leptina, adiponektina, interleukina 6, inhibitora aktivacije plazminogena 1, glukoze, glikiranog hemoglobina, kolesterola, triglicerida, HDL-a i LDL-a, izračunana je inzulinska rezistencija te utvrđena učestalost arterijske hipertenzije. Antropometrijske mjere ispitanica bile su najmanje u prvoj skupini, a najveće u četvrtoj. Poremećaj glikemije natašte nije imala nijedna ispitanica u prvoj skupini, u drugoj je 6,2% ispitanica imalo poremećaj, u trećoj 10,1% te u četvrtoj 16,4% ispitanica. Slična raspodjela pokazana je za poremećenu toleranciju glukoze, dijabetes tipa 2, arterijsku hipertenziju, učestalost pušenja i indeks tjelesne mase. Metabolički sindrom pokazao je sličnu raspodjelu, i to 22,6%, 36,9%, 46,4% te 49,1% u četvrtoj skupini, ukupno 38,6%. Pretile ispitanice imale su veću učestalost metaboličkog sindroma. Patološki promijenjene koncentracije adipokina uočene su u ispitanica s obzirom na indeks tjelesne mase te metabolički sindrom. Rezultati govore u prilog nepovoljnim dugoročnim posljedicama za zdravlje i većemu zdravstvenom riziku. Promjenom načina razmišljanja i nastavljanjem skrbi netom poslije porođaja pružit će se mogućnost ženama s GDM-om da smanje cjeloživotni zdravstveni rizik., Women with GDM have higher risk of disturbed glucose and lipids metabolism later in life, which, along with higher anthropometric measures and higher incidence of arterial hypertension, is the basis of metabolic syndrome. This cohort study involved women with GDM which have been monitored after delivery to ascertain the risk of developing glucose and lipid metabolism disorders, inflammation and metabolic syndrome, as well as to identify the earliest point in which it is possible to detect changes in potential disease markers. Along with anthropometric measures, concentrations of C-peptide, leptin, adiponectin, interleukin-6, plasminogen activation inhibitor-1, glucose, glycated hemoglobin, cholesterol, triglyceride, HDL and LDL have also been measured. Insulin resistance and arterial hypertension incidence have been calculated. The incidence of glucose intolerance, type 2 diabetes and metabolic syndrome has been determined. Women with GDM had higher incidence of glucose and lipids metabolism disorder, and metabolic syndrome compared to the healthy population, and have earlier disease onset. The results suggest poor longterm effects on health. Change in mindset and continuing with care right after delivery will provide women with GDM the ability to reduce the risk they live with.

Context Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse. Objective The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM). Design We analyzed data from the ongoing observational PREG study (NCT 04270578). Setting The study was conducted at the University Hospital Tübingen. Participants We examined 167 women (33 with GDM) during gestational week 27 ± 2.2. Intervention Subjects underwent 5-point OGTT with a 75-g glucose load. Main outcome measures We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome. Results Insulin secretion was significantly lower in women with GDM (P Conclusions The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.

Zhidan Wang,1 Alishba Hania,2 Asma Muzaffar,2 Saadia Zia2 1School of Education Science, Jiangsu Normal University, Xuzhou, 221116, People’s Republic of China; 2Department of Psychology, Institute of Southern Punjab, Multan, PakistanCorrespondence: Alishba Hania Email alishba_hania92@hotmail.comPurpose: Leading a normal life and managing daily psychological or physical stress is hard for everybody but when a person is diagnosed with gestational diabetes mellitus (GDM) during a widespread pandemic, the battle is inescapable. This research aimed to explore some positive dimensions that can lessen the adversities of these women.Design and Methods: We assessed all 200 cases of GDM who were registered in the maternity wards of the government and private hospitals of South Punjab, Pakistan. Respondents were diagnosed with GDM during the first wave of COVID-19. Post-traumatic growth (PTG) inventory, Family environment scale, and Partner supportive communication (PSC) scale were used. SEM and moderation analysis was conducted to test the hypothesized relationship among the variables.Results: Result showed that elicitation of thoughts and feelings (β = 0.109, t-value = 3.501, p = 0.001), effective listening (β = − 0.144, t-value = 1.928, p = 0.054), and communication towards partner (β = − 0.209, t-value = 4.850, p = 0.005) significantly moderated the relationship between family environment and post traumatic growth.Practical Implications: This research is beneficial for health practitioners because the trauma of being diagnosed with such a disease can be alleviated by the role of family environment and PSC.Keywords: post-traumatic growth, partner supportive communication, family environment, gestational diabetes mellitus, GDM, PSC, PTG

Purpose To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population. Methods We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities. Results The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P 1, all P P P Conclusions FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

Feifei Li, Xuexin Zhou, Decui Cheng, Hongkun Wang, Xianming Xu Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, People’s Republic of ChinaCorrespondence: Hongkun Wang; Xianming XuDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 650 New Songjiang Road, Songjiang District, Shanghai, 201600, People’s Republic of ChinaEmail annie_coco@163.com; xuxm11@163.comObjective: This study aimed to compare the incidence of gestational diabetes mellitus (GDM) in older underweight pregnant women vs young overweight/obese ones.Methods: A multiracial retrospective-cohort study was conducted in five hospitals of Shanghai on 7,485 women who had been pregnant during 2018– 2020. Incidence of GDM was equal to the proportion of GDM cases in the total number of cases observed in the same period. Comparison of GDM incidence of older underweight pregnant women and young overweight/obese ones was done with χ2 tests. ORs and 95% CIs for GDM were estimated using univariate and multivariate logistic regression across gestation age and prepregnancy BMI.Results: Advanced age (OR 1.09, 95% CI 1.072– 1.11; P=0) and higher BMI (OR 1.57, 95% CI 1.112– 2.212; P=0.01) were found to be risk factors of GDM. The incidence of 13.33% of older underweight pregnant women (age ≥ 35years, BMI < 18.5 kg/m2) developing GDM was lower than that of young overweight/obese ones (age ≤ 24 years, BMI ≥ 24 kg/m2). For those aged ≥ 35years, it is advised that BMI be kept to < 18.5 kg/m2. For those aged ≤ 24 years, BMI control should not exceed 24 kg/m2.Conclusion: Older underweight (age≥ 35years, BMI < 18.5 kg/m2) pregnant women beat young overweight/obese ones (age ≤ 24 years, BMI ≥ 24 kg/m2) on incidence of GDM. Factors influencing obesity/overweight in GDM were high maternal age, though being young is a promising protective factor for GDM and tolerance of BMI is promoted, but should be limited to certain ranges. Being older increased the chances of developing GDM, but those with lower BMI still had lower GDM incidence than younger pregnant women.Keywords: gestational diabetes mellitus, GDM, prepregnancy body-mass index, pre-BMI, pregnancy outcome

Aim: to identify the risk factors for gestational diabetes mellitus (GDМ) and predictors of perinatal lesions of central nervous system (CNS) combined with GDМ and maternal obesity.Materials and Methods. А retrospective observational case-control non-combined study was conducted to determine GDМ risk factors and their effect on perinatal pathology in 250 women divided into 2 groups. The main group included 150 pregnant women diagnosed with GDМ, the control group – 100 pregnant women without carbohydrate metabolism disorders. An assessment of hereditary, obstetric and gynecological history, as well as somatic health was carried out. Patients from the main group were subdivided into smaller groups: 1А (n = 77) – mothers whose newborns postnatally exerted adverse perinatal outcomes associated with impacting maternal hyperglycemia, and 1В (n = 73) – mothers whose newborns were born healthy. CHAID method (Chi Squared Automatic Interaction Detection) was used to create an algorithm for predicting adverse perinatal outcomes in GDМ. Аt the second stage, a single-center prospective observational non-combined cohort study was conducted to assess an effect of maternal hyperglycemia on formation of perinatal CNS lesions. Pre-labor concentration of neuron-specific enolase (NSE) was measured in the amniotic fluid of full-term fetuses in the group of pregnant women with GDM (n = 33) and in the group of pregnant women lacking carbohydrate metabolism disorders (n = 42).Results. Obesity, late reproductive age, family history of type 2 diabetes mellitus, abortions, early reproductive losses, macrosomic delivery in history are the main risk factors for GDM development. An algorithm was developed that allowed to predict a risk of newborn perinatal pathology in mother with GDM with an overall percentage of correct predictions of 68.7 ± 3.8 %. Pre-labor concentration of NSE in the amniotic fluid of full-term fetuses was elevated by 1.68 times (p = 0.006) in women with combined GDM and obesity (5.56 [3.37–6.24] ng/ml) compared to pregnant women with normal weight lacking carbohydrate metabolism disorders (3.29 [1.49–4.89] ng/ml).Conclusion. Pregnant women with obesity and type 2 diabetes mellitus familial history were featured with most prominent potential of developing perinatal complications. Rise in amniotic fluid NSE level in patients with GDМ corroborates damage of fetal CNS during antenatal period. The maximum NSE level was found in women comorbid with GDM and obesity.

Aim To investigate the expression of formyl peptide receptor 2 (FPR2) in maternal blood, umbilical blood, and placenta of patients with gestational diabetes mellitus (GDM), and to analyze the changes of other pro‐inflammatory cytokines in blood, including interleukin 33 (IL‐33), IL‐1β, tumor necrosis factor alpha (TNF‐α), and C‐reactive protein (CRP), so as to reveal the pathogenesis of GDM. Methods FPR2, IL‐33, IL‐1β, T TNF‐α, and CRP in maternal blood and umbilical cord blood of 50 pregnant women with GDM and 30 normal pregnant women were analyzed by ELISA method to explore the correlation between inflammatory factors and blood glucose. The expression of FPR2 in placental tissues was analyzed by PCR and immunohistochemistry. Results The expression of FPR2 in maternal blood of gestational diabetes patients was significantly higher than that of normal pregnant women, and other inflammatory factors IL‐33 and IL‐1β in maternal blood were also significantly increased. The expression of FPR2 in umbilical cord blood of gestational diabetes was higher than that of normal pregnant women, but the difference was not significant. Other inflammatory factors IL‐33, IL‐1β, and CRP in umbilical cord blood were also significantly increased. The expression of FPR2mRNA and protein in placental tissues of gestational diabetes was significantly higher than that of normal pregnant women. Conclusions The level of FPR2, IL‐33, and IL‐1β in maternal blood was related to the pathogenesis of GDM and these inflammatory factors could be used as special candidate direction of marks for the prevention, clinical treatment and drug design of GDM, laying a new theoretical foundation for the treatment of GDM.

Aims Gestational diabetes mellitus (GDM)-induced macrosomia is predominantly characterized by fat accumulation, which is closely related to adipocyte differentiation. An unknown long noncoding RNA RP11-290L1.3, referred to as RP11, was identified to be dramatically upregulated in the umbilical cord blood of women with GDM-induced macrosomia in our previous study. We conducted this study to identify the function of RP11 in GDM-induced macrosomia. Methods The effects of RP11 gain- and loss-of-function on HPA-v (human preadipocytes-visceral) adipogenesis were determined with lentivirus mediated cell transduction. The mRNA and protein expression levels of adipogenesis makers were evaluated by qPCR/Western blot. Then, we performed the microarray and pathway analysis to explore the possible mechanisms by which RP11 regulates adipogenesis. Results Overexpression of RP11 significantly enhanced adipocyte differentiation and increased the mRNA and protein expression levels of adipogenesis makers, such as PPARγ, SREBP1c, and FASN by qPCR/Western blot. Knockdown of RP11 showed opposite effects. Microarray and pathway analysis showed, after RP11 knockdown, 1612 genes were upregulated, and 583 genes were down-regulated which were found to be mainly involved in metabolic pathways, insulin signaling pathway and MAPK signaling pathway. Conclusion In conclusion, the unknown lncRNA RP11 serves as a positive factor on preadipocyte differentiation which could shed light on fetal fat accumulation in GDM.

Stephanie Dias,1,2 Sumaiya Adam,2 Paul Rheeder,3 Carmen Pheiffer1,4 1Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Cape Town, 7505, South Africa; 2Department of Obstetrics and Gynecology, University of Pretoria, Pretoria, 0001, South Africa; 3Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, 0001, South Africa; 4Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Cape Town, 7505, South AfricaCorrespondence: Carmen PheifferBiomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, 7505, South AfricaTel +27 21 938 0292Email carmen.pheiffer@mrc.ac.zaPurpose: Gestational diabetes mellitus (GDM) is a growing public health concern. GDM affects approximately 14% of pregnancies globally, and without effective treatment, is associated with short- and long-term complications in mother and child. Lower serum adiponectin (ADIPOQ) concentrations and aberrant DNA methylation have been reported during GDM. The aim of this study was to investigate the association between the ADIPOQ − 11377C>G and − 11391G>A, and methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms and GDM in a population of black South African women.Materials and Methods: DNA was isolated from the peripheral blood of 447 pregnant women with (n=116) or without (n=331) GDM, where after ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms were genotyped using TaqMan Quantitative Real-Time PCR analysis.Results: Women with GDM had a higher body mass index (p=0.012), were more insulin resistant (p< 0.001) and had lower adiponectin levels (p=0.013) compared to pregnant women with normoglycemia. Genotypic, dominant and recessive genetic models showed no association between ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms and GDM. Intriguingly, the risk G allele of ADIPOQ rs266729 was associated with higher fasting glucose and insulin concentrations, while the T allele in MTHFR rs1801133 was associated with higher fasting insulin concentrations only.Conclusion: ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms are not associated with GDM in a population of black South African women. These findings suggest that these single nucleotide polymorphisms (SNPs) do not individually increase GDM risk in the African population. However, the role of these SNPs in possible gene-gene or gene-environment interactions remain to be established.Keywords: SNP genotyping, molecular biomarkers, adiponectin, ADIPOQ, methylenetetrahydrofolate reductase, MTHFR, gestational diabetes mellitus, GDM

Objectives: To compare the reliability of non-fasting oral glucose tolerance test (OGTT) versus fasting OGTT for screening of hyperglycaemia in pregnancy (HIP). Methods: This cross sectional analytic study was conducted by the Department of Obstetrics & Gynaecology, Isra University Karachi Campus from October 2016 to April 2017. A total of 225 pregnant women irrespective of gestational age were included in the study. They underwent non fasting 75 grams OGTT. Venous plasma glucose was done 02 hours after the glucose load. Same women were advised to come again within three to seven days for fasting OGTT. Venous plasma glucose (VPG) was estimated in fasting and 2 hours post glucose load. Results: Using the non-fasting OGTT, out of 204 women, 32 were diagnosed with hyperglycemia. All these 204 women were again called for fasting OGTT three to seven days after the initial non-fasting OGTT. Only nine were diagnosed with hyperglycemia, out of these nine women, seven women who were screen positive on non-fasting OGTT were found to be screen positive on fasting OGTT as well. However, only two women were additionally diagnosed with hyperglycemia who were initially screen negative on non-fasting OGTT. The non-fasting OGTT has diagnosed HIP with sensitivity of 77.7%, specificity of 87.1%, positive predictive value of 21.8% and negative predictive value of 98.8%. Conclusion: The use of the non-fasting OGTT at first antenatal visit may be a practical approach to detect the HIP as screening and diagnostic tool in the resource constrained settings. doi: https://doi.org/10.12669/pjms.37.4.3979 How to cite this:Masood SN, Lakho N, Saeed S, Masood Y. Non-fasting OGTT versus Fasting OGTT for screening of Hyperglycaemia in Pregnancy (HIP). Pak J Med Sci. 2021;37(4):1008-1013. doi: https://doi.org/10.12669/pjms.37.4.3979 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Context: Gestational diabetes mellitus (GDM) is a recognized risk for abnormal glucose tolerance (AGT) long-term. Aims: The aim of this study is to determine the prevalence of postpartum diabetes and AGT and predictive factors among Sri Lankan women with GDM. Settings and Design: The follow-up study was conducted in Gampaha District, Sri Lanka. Materials and Methods: Pregnant women with GDM were identified by a community-based longitudinal study (n = 1200) by WHO 1999 criteria and followed up till 1 year postpartum. Study instruments were interviewer-administered questionnaire, anthropometric measurements, and fasting 75 gOGTT. Statistical Analysis Used: χ2 tests with P-values and odds ratios (ORs) with 95% confidence interval (CI) were used to assess the statistical significance and strength of the associations. Predictive factors of postpartum AGT were identified by the multivariate analysis. Results: Of those identified with GDM (194), 169 participated in postpartum follow-up at 2 months (87.1%). Of the 169, 59 participated at 1 year. At 2 months, 17/169 (10.1%) had diabetes and 55/169 (32.5%) had AGT (diabetes=17, impaired glucose tolerance= 36, impaired fasting glucose=2). At 1 year, 11/59 (18.6%) had diabetes and 28/59 (47.5%) had AGT. Predictive factors of postpartum AGT at 2 months were 2-h postprandial blood sugar (2-h PPBS) before 12 weeks ≥97.5 mg/dL (adjusted OR (aOR)=2.8; 95% CI=1.3–6.0), GDM diagnosis before 16 weeks (aOR=7.7; 95% CI=1.5–39.7), and 1-h oral glucose tolerance test (OGTT) ≥179 mg/dL (aOR=3.1; 95% CI=1.5–6.4). Predictive factors of postpartum AGT at 1 year were 2-h PPBS before 12 weeks ≥97.5 mg/dL (aOR=8.4; 95% CI=2.3–30.3) and physical activity (aOR= 0.2; 95% CI=0.1–0.8). Conclusion: Postpartum AGT following GDM is high among Sri Lankan women. Long-term follow-up is recommended.

Background Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women. Methods This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. Results An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054–1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650–0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). Conclusions The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

Context Accurate methods for early gestational diabetes mellitus (GDM) (during the first trimester of pregnancy) prediction in Chinese and other populations are lacking. Objectives This work aimed to establish effective models to predict early GDM. Methods Pregnancy data for 73 variables during the first trimester were extracted from the electronic medical record system. Based on a machine learning (ML)-driven feature selection method, 17 variables were selected for early GDM prediction. To facilitate clinical application, 7 variables were selected from the 17-variable panel. Advanced ML approaches were then employed using the 7-variable data set and the 73-variable data set to build models predicting early GDM for different situations, respectively. Results A total of 16 819 and 14 992 cases were included in the training and testing sets, respectively. Using 73 variables, the deep neural network model achieved high discriminative power, with area under the curve (AUC) values of 0.80. The 7-variable logistic regression (LR) model also achieved effective discriminate power (AUC = 0.77). Low body mass index (BMI) (≤ 17) was related to an increased risk of GDM, compared to a BMI in the range of 17 to 18 (minimum risk interval) (11.8% vs 8.7%, P = .09). Total 3,3,5′-triiodothyronine (T3) and total thyroxin (T4) were superior to free T3 and free T4 in predicting GDM. Lipoprotein(a) was demonstrated a promising predictive value (AUC = 0.66). Conclusions We employed ML models that achieved high accuracy in predicting GDM in early pregnancy. A clinically cost-effective 7-variable LR model was simultaneously developed. The relationship of GDM with thyroxine and BMI was investigated in the Chinese population.

Background Gestational diabetes mellitus (GDM) is a type of diabetes associated with pregnancy and may impose risks on both mother and fetus. Akt paeoniflorin was shown to have anti-inflammatory and anti-hyperglycemia properties and has a potential ability to suppress mammalian target of rapamycin (mTOR) signaling. The current study aimed to study the effect of paeoniflorin on GDM maternal, fetal, and placental characteristics in vivo. Methods Streptozotocin (STZ)-induced gestational diabetes rat model was used in our study. The expression levels of phosphorylation (p-) and total protein expression levels of protein kinase B (Akt), mTOR, serum/glucocorticoid regulated kinase 1 (SGK1), and eIF4E-binding protein 1 (4E-BP1) in the placenta were determined by Western blot assay. The blood glucose, insulin, and leptin levels were assessed using enzyme-linked immunosorbent assay (ELISA). Results We found that placental Akt/mTOR signaling was substantially upregulated in GDM patients compared with healthy donors. Paeoniflorin administration alleviates the dysregulation of blood glucose, leptin, and insulin levels in both maternal and fetal GDM rats. Paeoniflorin treatment suppressed the overactivation of Akt/mTOR signaling in placental tissues. More importantly, administration of paeoniflorin was beneficial for normalization of fetal size and body weight in the GDM rats. Conclusion Our study suggested that application of paeoniflorin may serve as a potential therapeutical strategy for patients with GDM.

Background: Our previous study revealed that astragaloside IV (AS-IV) effectively improved gestational diabetes mellitus (GDM) by reducing hepatic gluconeogenesis. Due to the importance of placental oxidative stress, we further explored the protective role of AS-IV on placental oxidative stress in GDM. Methods: First, non-pregnant mice were orally administrated with AS-IV to evaluate its safety and effect. Then GDM mice were orally administered with AS-IV for 20 days and its effect on the symptoms of GDM, placental oxidative stress, secretions of inflammatory cytokines, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway, were evaluated. Results: AS-IV had no adverse effect on non-pregnant mice. On the other hand, AS-IV significantly attenuated the GDM-induced hyperglycemia, glucose intolerance, insulin resistance, placental oxidative stress, productions of inflammatory cytokines and the activation of TLR4/NF-κB pathway. Conclusion: AS-IV effectively protected against GDM by alleviating placental oxidative stress and inflammation, in which TLR4/NF-κB might be involved.

Background and Aims: The association of gestational diabetes mellitus and serum Vitamin D levels in different trimesters of pregnancy has been studied recently. We conducted this study in an prospective observational cohort of well-characterized healthy pregnant women to examine the relationship between 1st trimester Vitamin D levels and Gestational Diabetes Mellitus (GDM) status during pregnancy. Methods: All pregnant women attending the out-patient department of Gynecology & Obstetrics, aged less than 35 years, and who were in their first trimester were included in the study. Socio-demographic, anthropometric details, clinical details, food frequency questionnaire and physical activity data was collected using validated pretested questionnaire. Results: The comparison between those with GDM and those with normal glucose levels has been illustrated. Women in the GDM are older than those in the non-GDM group. The women in GDM group were taller, heavier and their BMI was greater than those in the non-GDM group. There were no significant differences in dietary intake at baseline between mothers with GDM and those with normal glucose levels. Further, it was found that Vitamin D concentration of

Objective Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance which is diagnosed during pregnancy and poses considerable health risks for mother and child. Maternal body mass index (BMI) correlates with GDM diagnosis and the pathophysiology of this link may be explained through oxidative stress and mitochondrial dysfunction. In this study we investigate if mitochondrial dysfunction is evident in GDM by measuring cell free mitochondrial DNA concentration and determine if a potential relationship exists between maternal mitochondrial function and GDM diagnosis. Study design Plasma samples were taken at 20 weeks’ gestation from women who subsequently developed GDM (n = 44) and matched with women with uncomplicated pregnancies (n = 85) as controls. Control group 1 was matched by maternal age and BMI (n = 41) to GDM cases, while control group 2 was matched by maternal age alone (n = 44). Prediction potential was determined by binary regression analysis. Statistical analysis was performed on SPSS Statistics v25. Results Binary regression analysis showed a statistically significant association between mtDNA concentration and GDM diagnosis (p = 0.032) in GDM cases versus control group 2, indicating that GDM patients have higher circulating mtDNA concentrations relative to healthy control patients. The lack of statistical significance in control group 1 suggests that BMI may be linked to mitochondrial function in GDM patients. Conclusion These results demonstrate a potential pathogenic role for mitochondrial dysfunction in GDM, with BMI presenting as a likely physiological mediator.

Aims/hypothesis The aim of this work was to examine the progression to type 1 and type 2 diabetes after gestational diabetes mellitus (GDM) in a 23 year follow-up study. Methods We carried out a cohort study of 391 women with GDM diagnosed by an OGTT or the use of insulin treatment during pregnancy, and 391 age- and parity-matched control participants, who delivered in 1984–1994 at the Oulu University Hospital, Finland. Diagnostic cut-off levels for glucose were as follows: fasting, ≥4.8 mmol/l; 1 h, ≥10.0 mmol/l; and 2 h, ≥8.7 mmol/l. Two follow-up questionnaires were sent (in 1995–1996 and 2012–2013) to assess the progression to type 1 and type 2 diabetes. Mean follow-up time was 23.1 (range 18.7–28.8) years. Results Type 1 diabetes developed (5.7%) during the first 7 years after GDM pregnancy and was predictable at a 2 h OGTT value of 11.9 mmol/l during pregnancy (receiver operating characteristic analysis: AUC 0.91, sensitivity 76.5%, specificity 96.0%). Type 2 diabetes increased linearly to 50.4% by the end of the follow-up period and was moderately predictable with fasting glucose (AUC 0.69, sensitivity 63.5%, specificity 68.2%) at a level of 5.1 mmol/l (identical to the fasting glucose cut-off recommended by the International Association of Diabetes and Pregnancy Study Groups [IADPSG) and WHO]). Conclusions/interpretation All women with GDM should be intensively monitored for a decade, after which the risk for type 1 diabetes is minimal. However, the incidence of type 2 diabetes remains linear, and therefore individualised lifelong follow-up is recommended.

In recent years, diabetes has evolved into a non-communicable disease pandemic with data showing that one out of ten adults in the world have diabetes. Among various factors that contribute to this rising trend in diabetes, one factor that is of paramount importance is gestational diabetes mellitus (GDM). Maternal hyperglycemia sets off a vicious cycle that affects not only the mother and her child but also the generations to come. There are many criteria that are used for the diagnosis of GDM. Almost all of these criteria require the pregnant woman to be in the fasting state in order to perform an oral glucose tolerance test (OGTT). In many parts of the world, especially in low- and middle-income countries, OGTT is a resource-intensive and technically demanding procedure. More often than not, pregnant women do not attend the antenatal clinic fasting. If they are asked to come fasting again for the OGTT, the drop-out rate is increased. Thus, for practical purposes, a test that is feasible on the ground is essential. In this paper, we emphasize a "single-test" procedure wherein a 75-gram oral glucose load is administered to the pregnant woman irrespective of whether she is in the fasting state or not, and plasma glucose is measured at two hours. A plasma glucose value ≥ 140 mg/dL (7.8 mmol/L) at two hours is considered diagnostic of GDM. The single-test procedure was found to be a sustainable, cost-effective, evidence-based, and affordable test procedure for any society. It serves both as a screening test and a diagnostic test for GDM. Furthermore, we emphasize the need for universal screening of all pregnant women who attend the antenatal clinics to detect dysglycemia, especially in the early weeks of pregnancy when the impact on the growing fetus would be significant.

Metformin is one of the most easily available medications for diabetes and has a relatively low cost. It is not only used in diabetes but is also effective in polycystic ovarian syndrome (PCOS) and obesity. Although insulin is the first choice when it comes to treating pregnant women with gestational diabetes mellitus (GDM), metformin has also been debated as a good choice after modification of diet. As metformin passes through the placenta, it is essential to know its consequence of leading to insulin resistance in the fetus as well as the impact on postnatal development. The use of metformin during GDM has raised many trials demonstrating that outcomes from the use of metformin are similar to those achieved with insulin. Follow-up studies were also conducted that assessed the impact on children exposed to metformin in utero. This review highlights the experimental evidence relating to the use of metformin during pregnancy for different conditions, and its impact on the growth and development of offspring.

Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that succinate-SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between succinate-SUCNR1 axis and placental angiogenesis. In our in-vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.

Background Blood lipid increases during gestation are considered a physiological adaption, and decrease after delivery. However, some adverse pregnancy outcomes are thought to be related to gestational lipid levels. Therefore, it is necessary to have a reference range for lipid changes during gestation. The present study aims to describe triglyceride (TG) changes during pregnancy and 42 days postpartum and to find cut-off points for TG levels during the first, second, and third trimesters. Methods A total of 908 pregnant women were followed from recruitment to 42 days postpartum, and their serum lipids were collected at gestational weeks 6–8, 16, 24, and 36 and 42 days postpartum. The major outcome was postpartum hypertriglyceridemia. The association between gestational and postpartum TG levels was analysed by stepwise multiple linear regression. A two-stage approach including a linear mixed-effect model and linear or logistic regression was conducted to explore the contribution of the changes in TG over time in pregnancy to postpartum hypertriglyceridemia. Logistic regression was constructed to examine the association between gestational TG levels and postpartum hypertriglyceridemia. Cut-off points were calculated by receiver operating characteristic (ROC) curves. Results There was a tendency for serum TG to increase with gestational age and decrease at 42 days postpartum. Prepregnancy overweight, obesity, and GDM intensified this elevation. Higher TG levels at gestational weeks 6–8, 16, 24, and 36 were positively associated with a higher risk of postpartum hypertriglyceridemia [OR 4.962, 95 % CI (3.007–8.189); OR 2.076, 95 % CI (1.303–3.309); OR 1.563, 95 % CI (1.092–2.236); and OR 1.534, 95 % CI (1.208–1.946), respectively]. The trend of the change in TG over time was positively associated with the TG level and risk of postpartum hypertriglyceridemia [OR 11.660, 95 % CI (6.018–22.591)]. Based on ROC curves, the cut-off points of serum TG levels were 1.93, 2.35, and 3.08 mmol/L at gestational weeks 16, 24, and 36, respectively. Stratified analysis of prepregnancy body mass index (pre-BMI) and GDM showed that higher gestational TG was a risk factor for postpartum hypertriglyceridemia in women with normal pre-BMI and without GDM. Conclusions Gestational TG and its elevation were risk and predictive factors of postpartum hypertriglyceridemia, especially in pregnant women with normal pre-BMI or without GDM.

Despite extensive study, the role of air pollution in gestational diabetes remains unclear, and there is limited evidence of the beneficial impact of residential greenness on metabolic dysfunction during pregnancy. We used data from mothers in the Spanish INfancia y Medio Ambiente (INMA) Project from 2003–2008. We obtained spatiotemporally resolved estimates of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) exposures in early pregnancy and estimated residential greenness using satellite-based Normal Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding the mother’s residence. We applied logistic regression models to evaluate associations between each of the three exposures of interest and (a) glucose intolerance and (b) abnormal lipid levels. We found limited evidence of associations between increases in PM2.5 and NO2 exposures and the metabolic outcomes. Though not statistically significant, high PM2.5 exposure (≥25 µg/m3) was associated with increased odds of glucose intolerance (OR = 1.16, 95% CI: 0.82, 1.63) and high cholesterol (OR = 1.14, 95% CI: 0.90, 1.44). High NO2 exposure (≥39.8 µg/m3) was inversely associated with odds of high triglycerides (OR = 0.70, 95% CI: 0.45, 1.08). Whereas NDVI was not associated with glucose intolerance, odds of high triglycerides were increased, although the results were highly imprecise. Results were unchanged when the air pollutant variables were included in the regression models. Given the equivocal findings in our study, additional investigations are needed to assess effects of air pollution and residential greenness on metabolic dysfunction during pregnancy. This work is supported by a National Institute of Environmental Health Sciences (NIEHS) fellowship from the Training in Precision Environmental Health Sciences (TPEHS) Program (NIH Grant No. T32ES027801). E.S., K.W.W., and C.I.A. were partially supported by a NIEHS P30 Environmental Health Sciences Core Center grant (P30ES030285). The INMA study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, FIS-PI18/01142 incl. FEDER funds; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051, CPII18/00018), Generalitat de Catalunya-CIRIT 1999SGR 00241, EU Commission (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017, Department of Health of the Basque Government (2005111093), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.