Marker For Gestational Diabetes Mellitus Research Articles

Exploring Interleukin 6 as a Promising Marker for The Diagnosis of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a condition in which the ability of the mother's pancreatic β-cells to function properly is compromised. This leads to inadequate insulin production and, therefore, poor glucose regulation throughout pregnancy. In recent years, there has been a significant surge in interest in determining the impact of inflammation on the progression of GDM. Inflammatory factors may function as antagonists to insulin and induce insulin resistance. Interleukin -6 (IL-6), a kind of cytokine, significantly impacts the development of glucose intolerance and may be used as a possible indicator in the blood for early detection of glucose intolerance. This study aims to assess the potential role of IL6 as a prospective diagnostic marker for Gestational Diabetes mellitus. Our study is a case-control study started from September 2022 to June 2023 and enrolled 200 pregnant women aged between 15 and 45 years; cases included 100 patients selectively collected with a confirmed diagnosis of gestational diabetes mellitus in Kerbala obstetrics and gynecology hospital, and the control group included 100 healthy pregnant women also gathered from the obstetrics and gynecology hospital in Kerbala governorate. Results show that the mean of Interleukin 6 was significantly higher in pregnant women with GDM, with p-values of 0.05 and 0.001. these results suggest that Interleukin6 (IL6) can be used as a prospective diagnostic marker for GDM.

Mean Platelet Volume as a Predictive Marker for GDM

Background: Gestational Diabetes Mellitus (GDM) is defined as first onset of any glucose intolerance diagnosed in pregnancy and certain proportion has risk of developing type 2 diabetes later in life, but risk of type 1 is also increased. Screening at the earliest and enhanced diagnostic tools can help reduce burden of GDM and further progression as it is majorly a lifestyle disease. One of the easiest and cost-effective inflammatory markers are thrombocyte indices. Objective: To determine the potential value of MPV, an inexpensive and easy tool obtained from routine complete blood picture used to study morphology of platelet and whether it can be an indicator in prediction of GDM. Methods: Hospital based comparative study was done on 100 antenatal women attending OPD during first trimester. Case group includes women with recently diagnosed GDM as per guidelines of American diabetes Association by one-step 2-hour 75g OGTT and the cut off values were considered as per IADPSG. MPV is assessed amongst cases and controls and its association was studied in both groups. Results: The present study observed that MPV values of the GDM patients were significantly higher than those compared to normal pregnancies. The current investigation reveals that MPV values in GDM patients significantly exceed those observed in normal pregnancies. Specifically, the median MPV in the GDM group is 8.6 (IQR: 6.9-11.2), while in the non-GDM group, it is 7.4 (IQR: 4.8-10.4). The Mann-Whitney U test yielded a statistic of 905, with a corresponding p-value of 0.0175, which falls below the significance threshold of 0.05. Hence, there exists a statistically significant disparity in MPV between the groups. Conclusion: GDM is found to have underlying chronic inflammatory background and varied insulin resistance which states that these parameters may exist even before clinically diagnosable glucose intolerance occurs. This may direct that GTT might not detect GDM if done early in pregnancy, but inflammatory markers might diagnose as they have already been existing. One such economical marker is the MPV as a part of routine CBC. Keywords: Mean Platelet Volume; Gestational Diabetes Mellitus; IADPSG; Exclusive Real World Evidence

The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study-A controlled intervention study: Protocol paper.

Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. The study was registered on clinicaltrials.gov (NCT06110143).

Serum Glycome as a Diagnostic and Prognostic Factor in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a risk factor for both mother and fetus/neonate during and after the pregnancy. Inconsistent protocols and cumbersome screening procedures warrant the search for new and easily accessible biomarkers. We investigated a potential of serum N-glycome to differentiate between healthy pregnant women (n = 49) and women with GDM (n = 53) using a lectin-based microarray and studied the correlation between the obtained data and parameters of glucose and lipid metabolism. Four out of 15 lectins used were able to detect the differences between the control and GDM groups in fucosylation, terminal galactose/N-acetylglucosamine (Gal/GlcNAc), presence of Galα1,4Galβ1,4Glc (Gb3 antigen), and terminal α2,3-sialylation with AUC values above 60%. An increase in the Gb3 antigen and α2,3-sialylation correlated positively with GDM, whereas the amount of fucosylated glycans correlated negatively with the content of terminal Gal/GlcNAc. The content of GlcNAc oligomers correlated with the highest number of blood analytes, indices, and demographic characteristics, but failed to discriminate between the groups. The presence of terminal Gal residues correlated positively with the glucose levels and negatively with the LDL levels in the non-GDM group only. The results suggest fucosylation, terminal galactosylation, and the presence of Gb3 antigen as prediction markers of GDM.

Gestational diabetes mellitus and hypothyroidism: two sides of the same coin

Aim. To perform a systematic review of common risk factors and prognostic markers of gestational diabetes mellitus (GDM) and hypothyroidism (HT), as well as maternal and perinatal complications in these diseases. For achieving this task, we screened and analysed the relevant data from the publications in a PubMed database over the past 6 years.Key Points. A common risk factor for both diseases is obesity, which is characterized by pregestational insulin resistance, as well as the combination of by low-grade chronic inflammation and metabolic dysfunction termed as meta-inflammation. Antibodies to the thyroid-stimulating hormone receptor (TSHR) are associated with the reduced the risk of GDM. Studies on pathogenesis of pre-eclampsia in patients with GDM and HT have shown unequivocal results, although most of them suggest both HT and GDM as risk factors for the development of this pregnancy complication. Elevated levels of thyroid-stimulating hormone are associated with reduced antioxidant capacity and long-term endothelial activation. The heterogeneity of the anemia in GDM requires a rigorous differential diagnosis.Conclusion. GDM and HT are the most common endocrine diseases during pregnancy which significantly increase the risk of maternal and perinatal complications. Common risk factors, interrelationship, and ambiguous data on GDM and HT development mechanisms indicate the need for screening and detailed monitoring of patients with thyroid dysfunction for early detection and correction of hyperglycemia.

Do Serum Galectin-9 Levels in Women with Gestational Diabetes and Healthy Ones Differ before or after Delivery? A Pilot Study

Gestational diabetes mellitus (GDM) is a common metabolic disease that occurs during pregnancy, with the placenta playing an important role in its pathophysiology. Currently, the role of galectin-9 in the development of GDM is unknown. The aim of this study was to compare galectin-9 concentrations in healthy pregnant women and those with GDM. Galectin-9 levels were assessed in serum samples taken both just before and after delivery, as well as in urine samples collected in the postpartum period. Maternal body composition and hydration status were evaluated using the bioelectrical impedance analysis (BIA) method. There were no statistically significant differences in the concentration of galectin-9 in women with GDM compared to healthy pregnant women in their serum samples taken just before delivery, nor in their serum and urine samples collected in the early postpartum period. However, serum galectin-9 concentrations taken before delivery were positively correlated with BMI and parameters related to the amount of adipose tissue assessed in the early postpartum period. Additionally, there was a correlation between serum galectin-9 concentrations taken before and after delivery. Galectin-9 is unlikely to become a diagnostic marker for GDM. However, this subject requires further clinical research in larger groups.

Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes.

Exosomal microRNA (ExomiRs) serves as potential cargo molecules responsible for post-translation of gene expression and intracellular communication playing a vital role in acting as clinically relevant prognostic biomarkers for identifying pregnancy-associated complications in patients. ExomiRs are associated with Gestational Diabetes Mellitus (GDM) as potential targets for understanding the pathophysiology of beta-cell dysfunction. ExomiRs (ExomiR 122, ExomiR 16-5p, ExomiR 215-5p, ExomiR 450b-3p, ExomiR 122-5p) aid to act as biomarkers and regulate the progression of diabetes and its related complication. These ExomiRshave been reported to interfere with the regulation of various genes such as ZEB2, IRS1, IRS2, GLUT1, GLUT4, etc. and inhibition of several pathways like PI3K/AKT, Wnt, and mTOR signaling pathways leading to the modulation in the development of GDM affecting the clinical and pathological features of women. These ExomiRs have also been associated with other pregnancy-associated complications, including preeclampsia, hypothyroidism, pregnancy loss, and ectopic pregnancies. On the other hand, overexpression of certain ExomiRs such as Exomir-515-5p, ExomiR-221, and ExomiR-96 serve a regulatory role in overcoming insulin resistance. Taken together, the current review focuses on the prospective capabilities of ExomiRs for diagnosis and clinical prognosis of GDM women with respect to pregnancy outcomes.

Genetic predisposition to gestational diabetes mellitus in the Kazakh population

Background and aimsThe purpose of the study was to conduct a comparative analysis of population frequencies of alleles and genotypes of polymorphic variants of genes for impaired insulin synthesis and associated with insulin signal transduction. MethodsThis investigation uses a genomic database of 1800 conditionally healthy individuals of Kazakh ethnicity, who underwent full genome genotyping using OmniChip 2.5–8 Illumina chips of ∼2.5 million Single Nucleotide Polymorphism at deCODE Iceland Genomic Centre. ResultsThe highest frequency of carriage of minor A allele – 17.6% rs4607517 polymorphism of Glucokinase gene, unfavorable genotypes A/G – 29.5% and A/A – 3.0% in comparison with European and Asian populations, indicates a contribution of hereditary family forms of Maturity-onset diabetes of the young type 2 to gestational diabetes mellitus in Kazakh population. ConclusionsThe study of the associations of genetic markers of gestational diabetes mellitus will allow timely identification of high-risk groups before and at an early stage of pregnancy, carrying out the necessary effective preventive measures and, in the case of gestational diabetes mellitus development, optimizing the correction of carbohydrate metabolism disorders and predicting outcomes for the mother and the fetus.

Serum betatrophin levels and fatty acid profile in gestational diabetes mellitus: Correlation with insulin resistance

Introduction and Aim: Gestational diabetes mellitus (GDM) involves insulin resistance, altered levels of adipocytokines and inflammation. Interaction of various molecules in the pathogenesis of obesity and insulin resistance plays a major role in GDM. Angiopoietin-like protein 8, also named betatrophin is a hormone which is synthesized from liver and adipocytes. This molecule has beta cell-regenerating effect and is proposed to have therapeutic potential in obesity, insulin resistance and diabetes mellitus. The present study aimed to evaluate the role of betatrophin and free fatty acids (FFA) as markers of gestational diabetes mellitus (GDM). Materials and Methods: This study was conducted in Medical College Hospital on pregnant women with the normal body mass index. The study subjects were divided into 2 groups -one with healthy pregnant women and the other GDM and recruited for the study at 24 to 28 weeks of gestation. The levels of betatrophin, insulin and FFA were estimated in the serum and HOMA-IR was calculated. Results: Insulin resistance (IR), serum betatrophin level and plasma omega-6 fatty acid levels were higher, and plasma omega-3 fatty acid levels were lower among GDM subjects in comparison to healthy pregnant women. Fasting plasma glucose, serum betatrophin level and dihomo gamma linolenic acid level showed significant positive correlation with IR while omega 3 fatty acid %, levels of alpha linolenic acid, gamma linolenic acid and lauric acid showed negative correlation with IR in GDM women. Conclusion: Altered fatty acid profile in gestational diabetes mellitus indicated potential application of fatty acids as biomarkers of metabolic derangements which arise due to insulin resistance. The findings have diagnostic, prognostic, and therapeutic implications.

Identification of differential metabolites using untargeted metabolomics between gestational diabetes and normal pregnant women.

To study the metabonomics differences between pregnant women with gestational diabetes mellitus (GDM) in the third trimester and those in a group without GDM by screening a group of highly efficient and sensitive markers for GDM and validating previously published early metabolic markers of GDM. A cross-sectional cohort study based on ultra performance liquid chromatography tandem mass spectrometry untargeted metabolomics analysis of serum samples collected from 59 pregnant women with GDM and 59 pregnant women without GDM. A total of 121 metabolites were detected, and 27 were identified as differential metabolites between GDM and control. The combination of 27 metabolic peaks had area under curve (AUC) values of 0.90, 0.92, and 0.93 in the prediction models using support vector machine, partial least squares, and random forest, respectively. Finally, five metabolite biomarkers were selected to construct logistic regression models: L-valine, hypoxanthine, eicosapentaenoic acid, 2-amino-1,3,4-octadecanotriol, and choline. The AUC value of these metabolites was 0.769 between the GDM group and the control group. The discovery of a group of differential metabolites in pregnant women with GDM in the third trimester and in pregnant women without GDM may facilitate the study of the pathologic mechanism of GDM; it may be possible to find an efficient and sensitive alternative GDM detection method.

Maternal and Fetal Metabolites in Gestational Diabetes Mellitus: A Narrative Review.

Gestational diabetes mellitus (GDM) is a major public health issue of our century due to its increasing prevalence, affecting 5% to 20% of all pregnancies. The pathogenesis of GDM has not been completely elucidated to date. Increasing evidence suggests the association of environmental factors with genetic and epigenetic factors in the development of GDM. So far, several metabolomics studies have investigated metabolic disruptions associated with GDM. The aim of this review is to highlight the usefulness of maternal metabolites as diagnosis markers of GDM as well as the importance of both maternal and fetal metabolites as prognosis biomarkers for GDM and GDM’s transition to type 2 diabetes mellitus T2DM.

The Role of Placental Growth Factor in the Prediction of Carbohydrate and Thyroid Disorders during Pregnancy.

Background and objectives: To assess whether placental growth factor (PlGF) levels may have a predictive value for the onset of gestational diabetes mellitus (GDM) and thyroid dysfunction during pregnancy. Materials and Methods: This single-center retrospective analysis was conducted at the Specialized Hospital for Active Treatment in Obstetrics and Gynecology “Dr. Shterev”, Sofia, Bulgaria, from December 2017 to December 2019. Using pregnant women’s electronic records, we analyzed and compared the data of 412 women diagnosed with GDM and 250 women without evidence for carbohydrate disorders. Thyroid function was tested in all patients at the time of performing GDM screening. The following measurements were compared and assessed: body mass index (BMI), fasting blood glucose levels, thyroid-stimulating hormone levels (TSH), free thyroxine, and triiodothyronine (FT4 and FT3) levels, and serum placental growth factor (PlGF). The sensitivity and specificity of PlGF as a predictive marker for GDM and thyroid dysfunction were analyzed using receiver operating characteristic (ROC) curves. Results: There were no significant differences between GDM and control groups in terms of age and BMI (p > 0.05). In patients with established GDM, the PlGF corrected multiple of the median (MoM) was significantly higher compared to the control group (0.9 vs. 0.7, p < 0.001). The ROC-AUC for the prediction of GDM and thyroid dysfunction during pregnancy was 0.68 (95% CI 0.64–0.72) and 0.61 (95% CI 0.57–0.65), respectively. Conclusions: Our results underscore the potential role of PlGF as a biomarker in the prediction and diagnosis of GDM and thyroid dysfunction during pregnancy.

MiR-134-5p promotes inflammation and apoptosis of trophoblast cells via regulating FOXP2 transcription in gestational diabetes mellitus

ABSTRACT Gestational diabetes mellitus (GDM) is a prevalent and risky pregnant complication which warrants targeted therapy for restriction the inflammation and apoptosis of trophoblast cells. This study sought to analyze the aberrant expression and regulatory mechanism of microRNA (miR)-134-5p in GDM. The miR-134-5p expression in the serum of GDM patients and normal participants was detected via qRT-PCR, followed by receiver operating characteristic (ROC) curve analysis. In vitro GDM cell model was established in the HTR-8/SVneo cells using 25 mmol/L glucose, followed by transfection with miR-134-5p inhibitor and si-Forkhead box p2(FOXP2). The miR-134-5p and FOXP2 expressions, TNF-α, IL-1β, and IL-10 levels, cell proliferation, migration, and apoptosis were determined by a combination of qRT-PCR, western blot, ELISA, and cell counting Kit-8, Transwell assay, and flow cytometry. The binding relationship between miR-134-5p and FOXP2 was predicted and verified. Our results revealed that miR-134-5p was increased in the serum of GDM patients and could serve as a critical diagnostic marker for GDM. Moreover, miR-134-5p was upregulated in the high glucose (HG)-induced HTR-8/SVneo cells. The miR-134-5p inhibition suppressed the inflammation and apoptosis of HG-induced HTR-8/SVneo cells. miR-134-5p inhibited FOXP2 expression. FOXP2 expression was decreased in GDM. FOXP2 inhibition attenuated the function of miR-134-5p in HG-induced HTR-8/SVneo cells. Overall, miR-134-5p inhibited the FOXP2 expression to facilitate the inflammation and apoptosis of trophoblast cells, thereby exacerbating GDM.

Increased sulfiredoxin-1 levels as compensatory mechanism against reactive oxygen species in women with gestational diabetes mellitus

Objective:This study aimed to investigate the correlation between serum Sulfiredoxin-1 (Srx-1) levels and gestational diabetes mellitus (GDM).Materials and Methods A total of 40 patients diagnosed with GDM according to the American Diabetes Association Criteria and 40 age matched and gestational age-matched healthy pregnant women as a control group were included in this cross-sectional study. Serum Srx-1 levels and other demographic and laboratory variables were analyzed.Results:Fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), and Srx-1 levels were significantly different in patients with GDM than control (p<0.05). Plasma Srx-1 levels significantly correlated with fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, and HOMA-IR of patients with GDM (p<0.05), whereas no correlation in the control group.Conclusion:This is the first study demonstrating an association between serum Srx-1 levels and GDM. Our results suggest increased serum Srx-1 levels may be a novel predictive marker for GDM. More randomized-controlled trials are needed to evaluate Srx-1 as a marker for adverse fetal results; closer monitoring is warranted with high Srx-1 levels.

Gas Chromatography–Mass Spectroscopy-Based Metabolomics Analysis Reveals Potential Biochemical Markers for Diagnosis of Gestational Diabetes Mellitus

Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography–mass spectrometry (GC–MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, n = 24; aGT-GDM, n = 26; NGT, n = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α–hydroxybutyric acid (α–HB), β–hydroxybutyric acid (β–HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC–MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, n = 51; aGT-GDM, n = 44; and NGT, n = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8–14 gwk) who were NGT at this time, but in the second trimester (24–28 gwk) they were diagnosed with GDM. It was found that α–HB, β–HB, and several fatty acids were associated with aGT-GDM. A combination of α–HB, β–HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.

Role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for fetal and maternal complications in patients with gestational diabetes mellitus

Abstract Background Gestational diabetes mellitus (GDM) defined as glucose intolerance with onset or first diagnosis during pregnancy. While GDM usually resolves following delivery, it can have long-lasting health consequences, including increased risk for type 2 diabetes (T2DM) and cardiovascular disease (CVD) in the mother, and future obesity, CVD, T2DM, and/or GDM in the child. This contributes to a vicious intergenerational cycle of obesity and diabetes that impacts the health of the population as a whole. Fibroblast growth factor 21 (FGF21) is a hormone that is expressed predominantly in the liver, but also in other metabolically active tissues such as pancreas, skeletal muscle and adipose tissue. An elevated FGF21 level is also an independent predictor of T2DM. GDM and T2DM are proposed to have similar underlying pathophysiologies, raising the question of whether a similar relationship exists between FGF21 and GDM as it does with T2DM. Objectives assess the role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for maternal and fetal complications in patients with gestational diabetes mellitus (GDM). Patients and Methods A case control study that was conducted on 50 patients diagnosed with Gestational Diabetes Mellitus and 50 control subjects at Diabetes and Obstetrics outpatient clinic and inpatient ward at Ain Shams university hospitals in the period between December 2018 and July 2019. Patients diagnosed with gestational diabetes mellitus (GDM) at 24-28 weeks of gestation were included in this study. Results FGF 21 levels varied significantly with blood sugar values where higher levels of FGF 21 levels were found in patients with GDM with study results showing that FGF 21 can be used as a diagnostic marker for GDM at levels above 121 pg/ml with sensitivity 84% and specificity 92%. Conclusion FGF 21 can be used as a diagnostic marker for gestational diabetes. Further studies needed for better correlation between FGF 21 levels during pregnancy and maternal outcome.

Maternal serum sortilin levels in gestational diabetes mellitus

Objective To evaluate the serum sortilin levels in pregnant women with gestational diabetes mellitus (GDM) and to compare the results with normoglycemic healthy pregnant women and observe the relationship between serum sortilin levels and biochemical parameters. Methods This case–control study consisted of 55 pregnancies with GDM and 32 healthy singleton pregnancies matched for maternal and gestational age. The maternal serum levels of sortilin were measured with enzyme-linked immunosorbent assay and compared between groups. Results Sortilin levels were significantly higher in GDM group (5.52 ± 3.19 ng/mL versus 3.30 ± 1.47 ng/mL, p < .001). Pairwise comparisons showed that both the diet group and insulin group had significantly higher serum sortilin levels than the control group (p: .022 and p: .002, respectively). Maternal serum sortilin levels were significantly positively correlated with serum insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and glycated hemoglobin values (r: 0.277, p: .012, r: 0.306, p: .005, r: 0.267, p: .012, respectively). Conclusions Serum sortilin levels were significantly higher in women with GDM compared to the control group and were positively correlated with insulin, HOMA-IR and glycated hemoglobin levels. The present results point to the role of sortilin in glucose homeostasis and suggest that it may be a novel marker for GDM.

Hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus: a systematic review and meta-analysis

Purpose The relationship between hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus (GDM) have been studied extensively. However, conclusions remain debateable whether hepatokines are potential markers of GDM. We conducted a meta-analysis of published articles to understand the association between circulating levels of selected hepatokines (including FGF21, fetuin-A, afamin, adropin, ficolin-3, selenoprotein P, ANGPTL4 and AGF) and the risk of GDM. Materials and methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases for studies published before January 2021 that examined the association between hepatokines and GDM (Prospero Registration# CRD42020191408). The quality was assessed by the Newcastle–Ottawa Scale (NOS). Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of hepatokines in different groups using fixed effects or random effects models. Meta-regression analysis and publication bias were conducted in accordance with standard methods. The trim-fill adjustment method was used to further assess the possible effect of publication bias. Sensitivity analysis was performed by omitting each study one at a time. Results The meta-analysis included 31 observational studies relating hepatokine levels to GDM in 4729 participants (1908 GDM, 2821 non-GDM). Serum FGF21 levels in patients with GDM were higher than those in healthy pregnant women during the second trimester and after delivery (SMD 0.89, [95% CI] 0.01–1.78 for the second trimester; SMD 1.42, [95% CI] 0.86–1.98 for after delivery). The serum levels of afamin in patients with GDM were significantly higher than those in healthy pregnant women during the first trimester and before pregnancy (SMD 0.51, [95% CI] 0.15–0.86 for first trimester; SMD 0.97, [95% CI] 0.45–1.50 for before pregnancy). Serum adropin levels in patients with GDM were higher than those in healthy pregnant women during the first and third trimesters of pregnancy (SMD 4.26, [95% CI] 3.30–5.23 for the first trimester; SMD 4.02, [95% CI] 3.09–4.94 for the third trimester). The serum levels of ficolin-3 in GDM patients were higher than those in healthy pregnant women during the second and third trimesters of pregnancy (WMD 1.43, [95% CI] 0.91–1.96 for the second trimester; SMD 1.28, [95% CI] 0.72–1.84 for the third trimester). The serum AGF level of patients with GDM was higher than that of healthy pregnant women in the control group in the third trimester (WMD 61 [95% CI] 37.04–81.96). The serum levels of selenoprotein P in patients with GDM were higher than those in healthy pregnant women in the control group during the first trimester (WMD 7.09 [95% CI] 4.6–9.57). Conclusions Measurement of circulating hepatokines in the first or second trimester of pregnancy may improve the identification of women at risk of developing GDM later. Prospective evaluation of the combination of hepatokines and maternal characteristics for early identification of those who do and do not require OGTT is warranted. Additional well-designed prospective studies with longitudinal assessment of hepatokines during pregnancy are needed to understand the trajectories and dynamic associations of hepatokines with GDM risk.

Maternal circulating levels of Adipocytokines and insulin resistance as predictors of gestational diabetes mellitus: preliminary findings of a longitudinal descriptive study.

The present study aimed to assess the role of adipocytokines as predictive markers of gestational diabetes mellitus (GDM). We undertook this study to explore the association of adiponectin, resistin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and insulin resistance in the development of GDM. This longitudinal descriptive study was done in the Medical College Hospital, involving the departments of Biochemistry and Gynecology. The study subjects were pregnant women with normal body mass index. They were recruited at 12-14weeks of gestation, The healthy pregnant women were selected and were followed at 24-28weeks for screening of GDM. The participants were categorized as healthy and GDM based on oral glucose tolerance test results. Blood samples were collected on both the occasions at 12-14weeks and 24-28weeks. The serum samples were analyzed for levels of insulin, adiponectin, resistin, IL-6 and TNF-alpha. Insulin resistance (HOMA-IR) was calculated from serum insulin and plasma glucose values. The levels of HOMA-IR, resistin, IL-6 and TNF-alpha were significantly higher and level of adiponectin was significantly lower in GDM subjects in comparison to healthy pregnant women, when compared both at 12weeks and 24weeks. The levels of resistin, IL-6 and TNF-alpha were significantly higher and level of adiponectin was lower at 24weeks in comparison to 12weeks, in the healthy pregnant women as well as those with GDM . Significant difference in the levels of adipocytokines between the healthy and GDM pregnant women suggest potential clinical application of these molecules as biomarkers of GDM. The increase or decrease in the levels of adipocytokines during the course of pregnancy in GDM subjects suggests their role in GDM and potential use as predictive markers.

Early triglyceride and glucose index as a risk marker for gestational diabetes mellitus.

To assess the risk of gestational diabetes mellitus (GDM) according to the triglyceride and glucose (TyG) index values during the first trimester of pregnancy in Latin American women. Pregnant women were enrolled at their first prenatal visit at the Obstetric Division in the University Hospital "Dr. José E. González". Triglycerides and fasting plasma glucose (FPG) were collected to determine the TyG index. GDM diagnosis was performed by a single-step 2-hour 75-g oral glucose tolerance test. Generalized linear models were used to determine risk ratios; pregnancy outcomes at delivery were collected from the hospital medical records. A total of 164 pregnant women were included. GDM was present in 29 (17.7%) women. No significant differences in age, first-trimester body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), family history of diabetes, and TyG index were observed between GDM cases and the reference group without GDM. The adjusted analysis showed no association between TyG and GDM (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.57-1.88]). Higher TyG index values between women with and without a diagnosis of GDM in the second trimester were observed. No significant differences were identified in pregnancy outcomes, although a trend was observed for hyperbilirubinemia in women with first-trimester TyG index values greater than 8.7. Our findings do not support the use of the TyG index for GDM prediction in Latin American women.