Early Diagnosis Of Gestational Diabetes Mellitus Research Articles

Challenging the American College of Obstetricians and Gynecologists' Clinical Practice Update on Screening for Pre-existing Diabetes and Early Gestational Diabetes.

A recent American College of Obstetricians and Gynecologists Clinical Practice Update continues to recommend targeted (as opposed to universal) screening for pregestational diabetes, no longer recommends screening for early gestational diabetes mellitus (GDM), and provides updated guidelines for immediate postpartum testing for diabetes in patients with GDM. Here, we present data that the targeted screening paradigm, which has repeatedly been shown to fail in practice because of its complexity, no longer makes sense in the context of the high and rising prevalence of diabetes and diabetic risk factors, and we argue that the time has come for universal early pregnancy screening for pregestational diabetes. Furthermore, the recommendation against early screening for GDM is based on 2021 U.S. Preventive Services Task Force guidance, which in turn is based almost entirely on a single underpowered study that excluded individuals at highest risk and does not account for more recent research showing benefits of early diagnosis and treatment. Universal early pregnancy screening for pregestational diabetes may also help to identify patients at risk who will benefit from early GDM diagnosis and treatment and may provide rationale for prioritizing postpartum diabetes testing.

Prediction of Gestational Diabetes Mellitus Risk in Early Pregnancy Using Antenatal Screening Biomarkers

Aim: In this study, we aimed to compare their success in predicting the risk of Gestational Diabetes Mellitus (GDM) using demographic (age, gravidity, parity), body mass index (BMI), first-trimester fasting blood glucose (FBG), thyroid-stimulating hormone (TSH), and antenatal screening biomarkers (dual and quadruple tests). Materials and Methods: In this study, 800 pregnant women who underwent a one-step 75 g Oral Glucose Tolerance Test (OGTT) and antenatal screening tests at a tertiary hospital between January 2017 and June 2020 were retrospectively investigated. After patients were divided into two groups based on their GDM screening test results, the examined parameters were compared between the GDM-Positive and GDM-Negative groups. Once the parameters significantly associated with GDM were determined, their clinical utility in the early diagnosis of GDM was investigated. Results: GDM was diagnosed in 159 (19.8%) of 800 patients. The GDM-Positive group had a higher age, gravidity, parity, BMI, and first-trimester serum FBG levels, as well as lower serum PAPP-A MoM levels than the GDM-Negative group (P

Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM.

Identify gestational diabetes mellitus by deep learning model from cell-free DNA at the early gestation stage.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, which has significant adverse effects on both the mother and fetus. The incidence of GDM is increasing globally, and early diagnosis is critical for timely treatment and reducing the risk of poor pregnancy outcomes. GDM is usually diagnosed and detected after 24weeks of gestation, while complications due to GDM can occur much earlier. Copy number variations (CNVs) can be a possible biomarker for GDM diagnosis and screening in the early gestation stage. In this study, we proposed a machine-learning method to screen GDM in the early stage of gestation using cell-free DNA (cfDNA) sequencing data from maternal plasma. Five thousand and eighty-five patients from north regions of Mainland China, including 1942 GDM, were recruited. A non-overlapping sliding window method was applied for CNV coverage screening on low-coverage (~0.2×) sequencing data. The CNV coverage was fed to a convolutional neural network with attention architecture for the binary classification. The model achieved a classification accuracy of 88.14%, precision of 84.07%, recall of 93.04%, F1-score of 88.33% and AUC of 96.49%. The model identified 2190 genes associated with GDM, including DEFA1, DEFA3 and DEFB1. The enriched gene ontology (GO) terms and KEGG pathways showed that many identified genes are associated with diabetes-related pathways. Our study demonstrates the feasibility of using cfDNA sequencing data and machine-learning methods for early diagnosis of GDM, which may aid in early intervention and prevention of adverse pregnancy outcomes.

Longitudinal metabolomics integrated with machine learning identifies novel biomarkers of gestational diabetes mellitus

BackgroundEvidence from longitudinal studies is crucial to enhance our understanding of the role of metabolites in the progression of gestational diabetes mellitus (GDM). Herein, a longitudinal untargeted metabolomic study was conducted to reveal the metabolomic profiles and biomarkers associated with the progression of GDM, and characterize the changing patterns of metabolites. MethodsWe collected serum samples at three trimesters from 30 patients with GDM and 30 healthy Chinese pregnant women with pre-pregnancy BMI, age, and parity matched, and untargeted metabolomic analysis was performed, followed by machine learning approaches that integrated bootstrap and LASSO. Cluster analysis was conducted to elucidate the patterns of metabolite changes. Pathway analyses were conducted to gain insights into the underlying pathways involved. ResultsA total of 32 metabolites, mainly belonging to amino acid and its derivatives, were significantly associated with GDM across three trimesters, and were clustered into three distinct patterns. Metabolites belonging to phosphatidylcholines, lysophosphatidylcholines, lysophosphatidic acids, and lysophosphatidylethanolamines were consistently upregulated, and 2,3-Dihydroxypropyl dihydrogen phosphate was downregulated in GDM group. Amino acid-related, glycerophospholipid, and vitamin B6 metabolism were enriched in multiple trimesters. The levels of allantoic acid, which was positively correlated with blood glucose, was consistently higher in GDM patients and exhibited good discriminatory ability for GDM in the early and mid-pregnancy. ConclusionWe identified and characterized distinct patterns of metabolites associated with GDM throughout pregnancy, and found that allantoic acid was a potential biomarker for early diagnosis of GDM.

Timing of gestational diabetes diagnosis, gestational weight gains and offspring growth trajectory: a prospective birth cohort study

BackgroundThe evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood.MethodsA total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months.ResultsGDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04–1.36) and birth weight (OR 1.51, 95% CI 1.19–1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (β 0.16, 95%CI 0.03–0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (P < 0.001).ConclusionsExposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring.

The Effect of Timing and Methods for the Diagnosis of Gestational Diabetes Mellitus on Obstetric Complications.

Aim. To compare the impact of the time and method of diagnosis on gestational diabetes mellitus (GDM) in women who gave birth at the Hospital of the Lithuanian University of Health Sciences (LUHS) Kauno klinikos. Methods. A retrospective study was performed using data from the Department of Obstetrics and Gynecology of the LUHS Birth Registry to analyze the data of women who gave birth and had GDM in 2020-2021. The subjects were divided based on the type of diagnosis: GDM was diagnosed either at the first antenatal visit when fasting plasma glycemia (FPG) was ≥5.1 mmol/L (early diagnosis group) or after OGTT at 24 + 0 - 28 + 6 weeks of gestation when at least one pathological glycemic index was observed: fasting glycemia 5.1-6.9 mmol/L or 1-h glycemia ≥10.0 mmol/L or 2 h glycemia 8.5-11.0 mmol/L (late diagnosis group). The results were processed using IBM SPSS. Results. The early diagnosis group had 1254 (65.7%) women, the late diagnosis group had 654 (34.3%). More primigravida women were in the late diagnosis group (p = 0.017) while more multigravida were in the early diagnosis group (p = 0.033). The early diagnosis group had more obese women (p = 0.001), including those with a BMI > 40 (p = 0.001). In the early diagnosis group, GDM was more frequently diagnosed in women who gained <11 kg (p = 0.005), while in the late diagnosis group->16 kg (p = 0.001). FPG was higher in the early diagnosis group (p = 0.001). Glycemia was more commonly corrected with lifestyle changes in the late diagnosis group (p = 0.001), and with additional insulin therapy in the early diagnosis group (p = 0.001). Polyhydramnios and preeclampsia were more common in the late diagnosis group (p = 0.027 and p = 0.009). There were more large-for-gestational-age neonates in the late diagnosis group (p = 0.005). Macrosomia was more common in the late diagnosis group (p = 0.008). Conclusions. GDM is more commonly diagnosed with OGTT in primigravida women. Higher pregestational weight and BMI has an impact on the early diagnosis of GDM and need for insulin therapy with lifestyle changes. Late diagnosis of GDM is connected with obstetric complications.

Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis.

The association between biomarkers and the risk of gestational diabetes mellitus (GDM) or preeclampsia (PE) has been extensively studied. However, there is still a lack of convenient, specific, and sensitive indicators for early identification of GMD and PE. Therefore, we conducted a meta-analysis of published articles to investigate the value of afamin circulating levels in the early diagnosis of GDM and PE. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English studies published before November 16, 2022, that examined the association between afamin and GDM or PE. In addition, we searched Clinicaltrials.gov for the relevant completed and ongoing clinical trials. Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of afamin in different groups. Eleven studies were included in our analysis (N = 3047 participants: 1195 GDM, 1407 non-GDM, 195 PE, and 250 non-PE). Subgroup analysis based on different blood collection periods found that the plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women (SMD = 0.481, 95% CI: 0.280-0.682), but the analysis showed the opposite results in the second and late stages (SMD = 0.292, 95% CI: -0.092-0.676). The plasma afamin levels of pregnant women with PE in the first trimester (SMD = 0.808, 95% CI: 0.558-1.059) and second/third trimesters (SMD = 0.904, 95% CI: 0.570-1.239) were significantly higher than those in healthy pregnant women. The plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women, but the analysis showed the opposite results in the second and third trimesters. The plasma afamin levels in pregnant women with PE in the first, second, and third trimesters were significantly higher than those in healthy pregnant women. Additional large-scale prospective studies are desired to verify these findings, and it is recommended that afamin should be included as a routine diagnostic test for women with GDM and PE. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=339171, identifier CRD42022339171.

Commentary from the Italian Association of Medical Diabetologists (AMD) and Italian Society of Diabetology (SID) Interassociative Diabetes and Pregnancy Study Group on the screening and diagnostic methods for gestational diabetes: An open debate

The current board of the interassociative Italian association of medical diabetologists (AMD)/Italian society of diabetology (SID) Diabetes and Pregnancy Italian Study Group commented about two recent papers published in the New England Journal of Medicine that investigated the screening and diagnostic methods for gestational diabetes mellitus (GDM).It is well recognized that effective screening and accurate, early diagnosis of GDM contributes to better management of these women in order to reduce adverse maternal and fetal/neonatal outcomes. However, there is worldwide controversy concerning which screening (selective or universal; one step or two steps) and which diagnostic criteria (glucose thresholds) are appropriate. The main findings of these papers are discussed along with their implications for the management of pregnant women.

Circulating lncRNAs NONHSAT054669.2 and ENST00000525337 can be used as early biomarkers of gestational diabetes mellitus.

Early diagnosis can help prevent and reduce the adverse effects of gestational diabetes mellitus (GDM). This study intended to investigate key circulating long non-coding RNAs (lncRNAs) as novel biomarkers for diagnosis of GDM at the early stages. First, lncRNA microarray analysis was conducted for plasma samples of GDM women before delivery and 48 h after delivery. The expression of differentially expressed lncRNAs in clinical samples at different trimesters was randomly validated by quantitative polymerase chain reaction (PCR). Moreover, the correlation between lncRNA expression and oral glucose tolerance test (OGTT) level in GDM women during the second trimester was analyzed, followed by evaluating the diagnostic value of key lncRNAs during different trimesters using receiver operating characteristic (ROC) curve. Higher NONHSAT054669.2 expression and lower ENST00000525337 expression were revealed in GDM women before delivery relative to 48 h after delivery (P < 0.05). The expression of NONHSAT054669.2 and ENST00000525337 in GDM women during the first and second trimesters was dramatically higher than pregnant women (P < 0.05) with normal glucose tolerance (NGT). During the second trimester, NONHSAT054669.2 expression was positively related to OGTT level at 1 h (r = 0.41455, P < 0.001). Furthermore, ROC curve analysis revealed that ENST00000525337 alone, NONHSAT054669.2 alone, and their combination had high diagnostic value for GDM during the first (area under the ROC curve (AUC) = 0.979, 0.956, and 0.984, respectively) and second (AUC = 0.829, 0.809, and 0.838, respectively) trimesters (all P < 0.001). The plasma level of NONHSAT054669.2 and ENST00000525337 may be applied as novel diagnostic biomarkers for early diagnosis of GDM.

Placental Growth Factor and Pregnancy-Associated Plasma Protein-A as Potential Early Predictors of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and one of the main causes of adverse pregnancy outcomes. An early diagnosis of GDM is of fundamental importance in clinical practice. However, the major professional organizations recommend universal screening for GDM, using a 75 g oral glucose tolerance test at 24-28 weeks of gestation. A selective screening at an early stage of pregnancy is recommended only if there are maternal risk factors for diabetes. As a result, the GDM diagnosis is often delayed and established after the appearance of complications. The manifestation of GDM is directly related to insulin resistance, which is closely associated with endothelial dysfunction. The placenta, the placental peptides and hormones play a pivotal role in the manifestation and progression of insulin resistance during pregnancy. Recently, the placental growth factor (PlGF) and plasma-associated protein-A (PAPP-A), have been shown to significantly affect both insulin sensitivity and endothelial function. The principal function of PAPP-A appears to be the cleavage of circulating insulin-like growth factor binding protein-4 while PlGF has been shown to play a central role in the development and maturation of the placental vascular system and circulation. On one hand, these factors are widely used as early predictors (11-13 weeks of gestation) of complications during pregnancy, such as preeclampsia and fetal aneuploidies, in most countries. On the other hand, there is increasing evidence for their predictive role in the development of carbohydrate disorders, but some studies are rather controversial. Therefore, this review aims to summarize the available literature about the potential of serum levels of PlGF and PAPP-A as early predictors in the diagnosis of GDM.

The association between high hemoglobin levels and pregnancy complications, gestational diabetes and hypertension

Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are the principal causes of maternal morbidity and mortality. The maternal morbidity and mortality burden for women is relatively high, suggesting a substandard quality of care. Therefore, an early diagnosis of GDM and gestational hypertension (GH) can improve prenatal care for pregnant women and improve pregnancy outcomes. Previous studies demonstrated that elevated Hb levels in the first trimester indicate possible pregnancy complications and should not only be considered as good iron status. However, ethnic differences could play a role in determining the magnitude of the association. We hypothesized that high Hb levels (≥12.5 g/dl) in the first trimester (6-13 gestational weeks, GW) are associated with an increased risk of fasting blood sugar (FBS) ≥126 mg/dl, systolic blood pressure (SBP) ≥140 mmHg, and diastolic blood pressure (DBP) ≥90 mmHg among pregnant women visiting prenatal clinics.

Adiponectin, A-FABP and FGF-19 Levels in Women with Early Diagnosed Gestational Diabetes.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

Prevalence and Risk Factors of Gestational Diabetes Mellitus in Bangladesh: Findings from Demographic Health Survey 2017-2018.

Gestational diabetes mellitus (GDM) has serious consequences for both maternal and neonatal health. The growing number of noncommunicable diseases and related risk factors as well as the introduction of new World Health Organization (WHO) diagnostic criteria for GDM are likely to impact the GDM prevalence in Bangladesh. Our study aimed to assess the national prevalence and identify the risk factors using the most recent WHO criteria. We used the secondary data of 272 pregnant women (weighted for sampling strategy) from the Bangladesh Demographic and Health Survey 2017–2018. Multivariate logistic regression was performed to determine the risk factors of GDM. The overall prevalence of GDM in Bangladesh was 35% (95/272). Increased odds of GDM were observed among women living in the urban areas (adjusted odds ratio (aOR) 2.74, 95% confidence interval (CI) 1.43–5.27) compared to rural areas and those aged ≥25 years (aOR 2.03, 95% CI 1.13–3.65). GDM rates were less prevalent in the later weeks of pregnancy compared to early weeks. Our study demonstrates that the national prevalence of GDM in Bangladesh is very high, which warrants immediate attention of policy makers, health practitioners, public health researchers, and the community. Context-specific and properly tailored interventions are needed for the prevention and early diagnosis of GDM.

CircRNA circVEGFC is Highly Expressed in Gestational Diabetes Mellitus (GDM) and It is Correlated with Multiple Adverse Events.

BackgroundCircular RNA vascular endothelial growth factor C (circVEGFC) is a novel regulator of glucose metabolism, while its role in gestational diabetes mellitus (GDM) is unclear. This study aimed to detect the expression of circVEGFC in GDM and explore its clinical values.MethodsThis study enrolled 220 pregnant women (gestational age less than 5 weeks) with normal blood glucose level on the day of admission. The expression of circVEGFC in plasma samples of these participants was determined by RT-qPCR. The participants were divided into high and low circVEGFC level groups with the median expression level of plasma circVEGFC as the cutoff value. The development of GDM was monitored until delivery. Adverse events were also monitored.ResultsCompared to low circVEGFC level group, GDM-free curve analysis revealed significantly higher incidence of GDM in high circVEGFC level group. In addition, plasma expression levels of circVEGFC were also higher in GDM patients than that in non-GDM patients on the day of admission and at 1 month before and after delivery. ROC curve analysis revealed that high expression levels of circVEGFC on the day of admission showed higher sensitivity and specificity in the early diagnosis of GDM. Moreover, high circVEGFC level group showed higher incidence rates of fetal malformation and hypertension.ConclusionTherefore, circVEGFC is highly expressed in GDM, and it is correlated with multiple adverse events.

The Association Between High Hemoglobin Levels and Pregnancy Complications, Gestational Diabetes and Hypertension, Among Palestinian Women.

Introduction: Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are the principal causes of maternal morbidity and mortality. The maternal morbidity and mortality burden for Palestinian women is relatively high, suggesting a substandard quality of care. Therefore, an early diagnosis of GDM and gestational hypertension (GH) can improve prenatal care for pregnant women and improve pregnancy outcomes. Previous studies demonstrated that elevated Hb levels in the first trimester indicate possible pregnancy complications and should not only be considered as good iron status. However, ethnic differences could play a role in determining the magnitude of the association. We hypothesized that high Hb levels (≥12.5 g/dl) in the first trimester (6-13 gestational weeks, GW) are associated with increased risk of fasting blood sugar (FBS) ≥126 mg/dl, systolic blood pressure (SBP) ≥140 mmHg, and diastolic blood pressure (DBP) ≥90 mmHg among pregnant Palestinian women visiting prenatal clinics in Palestine.Methods: Medical records (N=5263) were reviewed for singleton pregnancies who had their first maternity care clinic visit (6-13 GW) at primary healthcare centers of the Palestinian Ministry of Health in the north of the West Bank in 2018 and 2019. Women were excluded if they had FBS ≥92 mg/dl, SBP ≥140 mmHg, DBP ≥90 mmHg, ultrasound-based gestational age >13 weeks, or who were previously diagnosed with diabetes mellites, GDM, hypertension, GH, taking drugs for these conditions, or were smoking during pregnancy. Hb levels in g/dl were divided to low (<11.0), normal (11-12.49), and high (≥12.5). The associations between high hemoglobin levels and pregnancy complications in pregnant women were assessed by calculating the odds ratios (OR) and their 95% confidence intervals (CIs) using logistic regression. P-values of <0.05 were considered significant.Results: The final number of eligible records was 2565. Pregnant women with high Hb levels in the first trimester were at higher risk of high FBS (≥126 mg/dl; OR=2.99, 95%CI, [1.675-5.368]) and high systolic blood pressure (≥140 mmHg; OR=3.048, 95%CI, [1.252-7.421]) at 24 GW. Gravidity was significantly associated with decreased risk of high FBS (OR=0.838, 95%CI [0.704-0.991]).Conclusion: Our findings suggest that Hb level at registration could be utilized in predicting the risk of GDM and HP among Palestinian women who never had a previous history of these conditions. The results of this study could have important clinical implications for early screening, which could improve preventive and curative health services to promote the health of pregnant women and children.

Early markers of gestational diabetes mellitus: what we know and which way forward?

Women’s metabolism during pregnancy undergoes numerous changes that can lead to gestational diabetes mellitus (GDM). The cause and pathogenesis of GDM, a heterogeneous disease, are not completely clear, but GDM is increasing in prevalence and is associated with the modern lifestyle. Most diagnoses of GDM are made via the guidelines from the International Association of Diabetes and Pregnancy Study Groups (IADSPG), which involve an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. Diagnosis in this stage of pregnancy can lead to short- and long-term implications for the mother and child. Therefore, there is an urgent need for earlier GDM markers in order to enable prevention and earlier treatment. Routine GDM biomarkers (plasma glucose, insulin, C-peptide, homeostatic model assessment of insulin resistance, and sex hormone-binding globulin) can differentiate between healthy pregnant women and those with GDM but are not suitable for early GDM diagnosis. In this article, we present an overview of the potential early biomarkers for GDM that have been investigated recently. We also present our view of future developments in the laboratory diagnosis of GDM.

Interleukin-33 and its receptor soluble suppression of tumorigenicity 2 in the diagnosis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common pregnancy-related disease that increases the risk of metabolic disorders for the pregnancies and their offspring. GDM could be effectively prevented by early diagnosis and timely treatment. 120 patients with GDM and 108 gestational week-matched pregnancies with normal glucose tolerance (NGT) were enrolled in our study. Their blood samples were collected, and demographic characteristics were analysed. Compared to NGT pregnancies, patients with GDM had increased the secretions of interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), IL-6 and tumour necrosis factor-α (TNF-α) in their plasma with elevated homeostatic model assessment (HOMA). Moreover, IL-33/sST2 was positively correlated with HOMA, IL-6 and TNF-α levels in the plasma of patients with GDM respectively. IL-33/sST2 might serve as a novel potential biomarker for early diagnosis of GDM.

Early diagnosed gestational diabetes mellitus is associated with adverse pregnancy outcomes: A prospective cohort study

Context The significance of an early diagnosis of gestational diabetes mellitus (GDM) with oral glucose tolerance test (OGTT) has not been determined. Objective The objective of this work is to investigate GDM diagnosed by early and standard OGTTs and determine adverse maternal and neonatal outcomes associated with early GDM diagnosis. Research design and methods The Early Diagnosis of Gestational Diabetes Mellitus study is a prospective cohort study. Each participant in the study underwent 2 OGTTs, an early OGTT at 18 to 20 gestational weeks (gws) and a standard OGTT at 24 to 28 gws. The reproduciblity between early and standard OGTT were analyzed. Maternal and neonatal metabolic disorders and pregnancy outcomes were compared across groups. Results A total of 522 participants completed both the early and standard OGTTs. The glucose values in the early OGTT were not significantly different from those in the standard OGTT (fasting: 4.31 ± 0.41 mmol/L vs 4.29 ± 0.37 mmol/L, P = .360; 1-hour: 7.68 ± 1.71 mmol/L vs 7.66 ± 1.59 mmol/L, P = .826; 2-hour: 6.69 ± 1.47 mmol/L vs 6.71 ± 1.39 mmol/L, P = .800). The reproducibility of early and standard OGTT results was 74.9%. Pregnant women in the GDM group had higher glycated hemoglobin, C-peptide, and homeostasis model assessment of insulin resistance in the late gestational period. Neonates born to mothers in the GDM group were at a higher risk of being large for gestational age (odds ratio [OR]: 3.665; 95% CI, 1.006-11.91) and were also more prone to neonatal hyperinsulinemia (OR: 3.652; 95% CI, 1.152-10.533). Conclusion Early-onset GDM diagnosed by OGTT at 18 to 20 gws is associated with maternal and neonatal metabolic disorders and adverse pregnancy outcomes. Further randomized controlled trials on the therapeutic efficacy for early-onset GDM will confirm the significance of early screening for GDM.

Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus.

The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM.