Gestational Diabetes Mellitus Subjects Research Articles

Clinical significance of the genetically variable landscape of the gut microbiome in patients with gestational diabetes mellitus patients

BackgroundThe composition of the gut microbiome has been recorted to be strongly associated with gestational diabetes mellitus (GDM), but mutational characterization of the microbiome in patients with GDM has been overlooked. Here, we revealed the genetic variation landscape of the gut microbiome and assessed its clinical significance in a cohort of patients with GDM. MethodsWe employed a macrogenomic dataset made up of a discovery cohort of 54 cases and a validation cohort of 220 cases to screen for high-abundance microbial flora and identified single nucleotide variants (SNVs) and insertions/deletions (indels). Subsequently, we analyzed the mutation spectra of genomes of the intestinal flora by using the previously identified SNVs and identified mutation signatures. Additionally, we utilized the Random Forest algorithm to identify key differential SNVs and elucidated their biological functions and associations with the clinicopathological parameters of GDM. ResultsWe screened 15 key microbial flora and found that the GDM group had more SNVs and indels in the intestinal flora than the control group, with a significant increase in C > T and T > C base mutations and were more susceptible to sequence mutations. Compared to the control group, the GDM group underwent a more significant evolution, as evidenced by the presence of a unique mutational spectrum and mutational characteristics. Random Forest algorithm analysis showed that the combined characterization of five gut microbial species and 21 SNV-related markers was effective in distinguishing between GDM and control subjects in both discovery (area under the curve (AUC) = 0.86) and validation (AUC = 0.73) sets. These markers also revealed that GDM is strongly associated with sphingolipids, galactose, and proteins containing the DUF structural domain. ConclusionsThe GDM intestinal flora has unique mutational features that correlate significantly with clinicopathological involvement and may be involved in the development of the disease.

Fetal abdominal obesity in women with one value abnormality on diagnostic test for gestational diabetes mellitus.

Previous studies have shown that fetal abdominal obesity (FAO) was already observed at the time of gestational diabetes mellitus (GDM) diagnosis and persisted until delivery despite management in older and/or obese women. In this study, we investigated whether fetuses of women with milder hyperglycemia than GDM have accelerated abdominal growth, leading to adverse pregnancy outcomes. We retrospectively reviewed the medical records of 7,569 singleton pregnant women who were universally screened using a 50-g glucose challenge test (GCT) and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT result was ≥140mg/dL. GDM, one value abnormality (OVA), and normal glucose tolerance (NGT, NGT1: GCT negative, NGT2: GCT positive & OGTT negative) were diagnosed using Carpenter-Coustan criteria. With fetal biometry data measured simultaneously with 50-g GCT, relative fetal abdominal overgrowth was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference(AC) per actual GA by the last menstruation period(LMP), biparietal diameter(BPD) or femur length(FL), respectively. FAO was defined as FAOR ≥90th percentile The FAORs of GA-AC/GA-LMP and GA-AC/GA-BPD were significantly higher in OVA subjects compared to NGT subjects but not in NGT2 subjects. Although the frequency of FAO in OVA (12.1%) was between that of NGT (9.6%) and GDM (18.3%) without statistically significant difference, the prevalence of large for gestational age at birth and primary cesarean delivery rates were significantly higher in OVA (9.8% and 29.7%) than in NGT (5.1% and 21.5%, p<0.05). Particularly, among OVA subjects with FAO, the prevalence (33.3% and 66.7%) was significantly higher than in those without FAO (9.7% and 24.2%, p<0.05). The degree of fetal abdominal growth acceleration in OVA subjects was intermediate between that of NGT and GDM subjects. OVA subjects with FAO at the time of GDM diagnosis were strongly associated with adverse pregnancy outcomes.

Epicardial fat thickness in patients with gestational diabetes mellitus and its association with N-terminal pro-brain natriuretic peptide.

The female population with gestational diabetes mellitus (GDM) has a postpartum profile with increased cardiovascular (CV) risk factors and heightened prospective CV risk. Epicardial fat tissue was reported to be related to cardiometabolic diseases as metabolically active adipose tissue and natriuretic peptides (NPs) have been shown to have metabolic effects. This study's aim was to determine the relationship between epicardial fat thickness (EFT) and NPs in the female population diagnosed with GDM. The study involved 161 pregnant women: 96 with GDM, and 65 healthy controls. GDM was diagnosed following the American Diabetes Association (2013) norms for diagnosing diabetes. All patients underwent echocardiography to measure EFT. N-terminal pro-brain natriuretic peptide (NT-proBNP) and other parameters were quantified in blood samples. The Independent Samples t-test, Pearson's correlation test, and a multivariable logistic regression analysis (LRA) were performed for statistical evaluation. A p-value <0.05 was considered statistically significant. Fasting (91.46±14.29 mg/dl vs. 82.18±8.21 mg/dl) (p<0.001), first-hour (202.30± 21.60 mg/dl vs. 161.57±16.21 mg/dl) (p<0.001), and second-hour (176.95±20.43 mg/dl vs. 130.93±16.95 mg/dl) glucose levels (p<0.001), fasting insulin level (14.54±3.50 mUL/mL vs. 11.51±2.04 mUL/mL; p<0.001), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value (3.28±0.99 vs. 2.31±0.45; p<0.0001) in GDM Group were significantly higher than Control Group. The GDM Group also had significantly increased EFT values compared to the Control Group (4.74±0.65 mm vs. 3.77±0.66 mm; p<0.0001), whereas NT-proBNP levels of diabetic women were considerably lower compared to controls (21.59±19.86 pg/ml vs. 39.74±33.96 pg/ml; p<0.0001). In addition, EFT thickness and the NT-proBNP level were determined to be significantly negatively correlated (r=-32, p<0.0001). EFT evaluation might play a prognostic role in detecting cardiometabolic risk associated with potential disorders such as GDM. This study showed a potential interplay between epicardial adipose tissue and NPs secreted by cardiomyocytes and practical effects on fat metabolism in GDM subjects.

Potential Protective Effect of Anti-zinc Transporter 8 Autoantibodies on Gestational Diabetes Mellitus in Iraqi Population

Background: The human zinc transporter 8 (ZNT8), also known as the solute carrier family 30A, member 8 (SLC30A8), is a β-cell specific integral membrane protein, mainly restricted to the membrane of insulin secretory granules. ZnT8 plays a crucial role in both insulin synthesis and secretion as well as the viability of β-cells. The recently identified autoantibodies targeting the β-cell surface epitopes of ZnT8 have been proposed as a new risk factor for gestational diabetes mellitus (GDM). Due to the lack of prior research studies on the role of β-cell surface autoantibodies against ZnT8 in the immunologic etiology of GDM in Iraqi population, this study has been designed to explore the association between the rs13266634 C&gt;T polymorphism in the SLC30A8 gene and the serum levels of ZnT8 as well as Zinc Transporter-8 Autoantibody (ZnT8A) in women diagnosed with GDM. Methods: A total of 50 participants with GDM and 50 controls from the Baghdad Teaching Hospital/Pregnancy Care unit at the Medical City, Baghdad, Iraq, were recruited in this case–control study. Serum levels of ZnT8 and ZnT8A were assayed with enzyme-linked immunosorbent assay, and Taqman real time polymerase chain reaction (RT-PCR) was used for rs13266634 single nucleotide polymorphism (SNP) genotyping. Results: ZnT8A levels were significantly lower in women with GDM than non-GDM women (P ≤ 0.01). A ZnT8A level lower than 20.0 pg/mL was significantly associated with a threefold higher risk for GDM with P ≤ 0.001. ZnT8 levels were significantly higher in the GDM subjects (P ≤ 0.05). The T allele at the rs13266634 C&gt;T SNP significantly conferred a higher risk of GDM (P = 0.002). In view of that, the TT genotype, compared to the CC genotype, showed a significant association with increased GDM risk (P ≤ 0.01). Serum ZnT8A concentrations were significantly low among GDM women who had CT genotype (P = 0.003). Conclusion: The T variant at the SLC30A8 rs13266634 C&gt;T polymorphism appears to play a key role in determining the β-cell autoimmunity by inducing an autoantibody response due to its hyperactivity of zinc transportation.

Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study.

Glyoxalase 1 (GLO1) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the GLO1 gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between GLO1 and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of GLO1 SNPs and GDM risk. The study included a total of 500 GDM patients and 502 control subjects. The SNPscan™ genotyping assay was used to genotype rs1781735, rs4746 and rs1130534. To assess the disparities in genotype, allele, and haplotype distributions and their correlation with GDM risk, the independent sample t-test, logistic regression, and chi-square test were employed during the data processing phase. Furthermore, one-way ANOVA was conducted to determine the differences in genotype and blood glucose and methylglyoxal(MG) levels. Significant differences were observed in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and parity between GDM and healthy subjects (P < 0.05). After adjusting for these factors, GLO1 rs1130534 TA remained associated with an increased risk of GDM (TA vs. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; P = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA vs. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; P = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (P < 0.05). Conversely, the GLO1 rs4746 TG was associated with a decreased risk of GDM (TG vs. TT: OR = 0.740; 95% CI: 0.548-0.999; P = 0.049; TG vs. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; P = 0.048). Additionally, the haplotype T-G-T of rs1781735, rs4746 and rs1130534 was associated with a decreased risk of GDM among individuals with a pre-BMI ≥ 24 (OR = 0.423; 95% CI: 0.188-0.955; P = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (P < 0.05). Our findings suggested that GLO1 rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but GLO1 rs4746 was associated with a decreased risk of GDM. The rs1781735 has been associated with the accumulation of maternal MG and subsequent weight gain in neonates.

Impact of vitamin D resistance genes on vitamin D deficiency during pregnancy among the South Indian population

Increasing evidence suggests that vitamin D (Vit-D) could be pivotal in maintaining normal glucose homeostasis. Low levels of Vit-D in early pregnancy are associated with a higher risk of gestational diabetes mellitus (GDM). Though several reports have highlighted the prevalence of vit-D deficiency among pregnant women, its underlying cause has not yet been fully elucidated. In this connection, a few studies have found the development of resistance to Vit-D, including the levels of Vitamin D receptor (VDR) and transcription regulators that modify VDR action, as well as the bioavailability of Vit-D. We aimed to determine the levels of Vit-D resistance genes such as 25-HydroxyVit-D-24-hydroxylase (CYP24A1), VDR repressor genes (SNAIL and SMRT) and their association between Vit-D concentrations in early pregnancy, and the risk of gestational diabetes mellitus (GDM). A prospective observational study was conducted on healthy pregnant women (NGDM; n = 50) and GDM (n = 50) attending routine antenatal care at SRM Medical College Hospital, Chennai, recruited at 12 weeks of gestation. We found that the serum levels of Vit-D were low in GDM subjects and negatively correlated with the fasting glucose levels. Further, increased expressions of Vit-D resistance genes such as CYP24A1, SNAIL, and SMRT were observed in GDM subjects and negatively correlated with the serum levels of Vit-D. Furthermore, we have validated the data using the trophoblast cell line, BeWo, exposed to calcitriol under a hyperglycemic environment. Our finding showed that increased expression of Vit-D resistance genes in pregnancy may be associated with a greater risk of adverse pregnancy outcomes, including GDM.

Gut microbiome interacts with pregnancy hormone metabolites in gestational diabetes mellitus.

Change in the composition of intestinal microbiota is associated with metabolic disorders such as gestational diabetes mellitus (GDM). To understand how the microbiota impacts the development of gestational diabetes mellitus, we profiled the intestinal microbiome of 54 pregnant women, including 27 GDM subjects, by employing 16S rRNA gene sequencing. Additionally, we conducted targeted metabolomics assays to validate the identified pathways with overrepresented metabolites. We evaluated the patterns of changing abundances of operational taxonomic units (OTU) between GDM and the healthy counterparts over three timepoints. Based on the significant OTUs, we inferred 132 significantly altered metabolic pathways in GDM. And identified two overrepresented metabolites of pregnancy hormone, butyrate and mevalonate, as potential intermediary metabolites of intestinal microbiota in GDM. Finally, we validated the impacts of the intestinal microbiota on GDM by demonstrating consistent changes of the serum levels of progesterone, estradiol, butyrate, and mevalonate in an independent cohort. Our findings confirm that alterations in the microbiota play a role in the development of GDM by impacting the metabolism of pregnancy hormones. This provides a novel perspective on the pathogenesis of GDM and introduces potential biomarkers that can be used for early diagnosis and prevention of the disease.

Individualized network analysis reveals a link between the gut microbiome, diet intervention and Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM), a serious complication during pregnancy which is defined by abnormal glucose regulation, is commonly treated by diabetic diet and lifestyle changes. While recent findings place the microbiome as a natural mediator between diet interventions and diverse disease states, its role in GDM is still unknown. Here, based on observation data from healthy pregnant control group and GDM patients, we developed a new network approach using patterns of co-abundance of microorganism to construct microbial networks that represent human-specific information about gut microbiota in different groups. By calculating network similarity in different groups, we analyze the gut microbiome from 27 GDM subjects collected before and after two weeks of diet therapy compared with 30 control subjects to identify the health condition of microbial community balance in GDM subjects. Although the microbial communities remain similar after the diet phase, we find that the structure of their inter-species co-abundance network is significantly altered, which is reflected in that the ecological balance of GDM patients was not "healthier" after the diet intervention. In addition, we devised a method for individualized network analysis of the microbiome, thereby a pattern is found that GDM individuals whose microbial networks are with large deviations from the GDM group are usually accompanied by their abnormal glucose regulation. This approach may help the development of individualized diagnosis strategies and microbiome-based therapies in the future.

1201-P: Circulating C1q/TNF-Related Protein 6 (CTRP6) and CTRP9 as Potential Biomarkers for Early Gestational Diabetes Mellitus

Background: The growing evidence has been verified that C1q/TNF-related protein 6 (CTRP6) and CTRP9, secreted by adipose tissue, can regulate glucose and lipid metabolism. However, the effect of CTRP6 and CTRP9 in gestational diabetes mellitus (GDM) is scarcely known. This study aimed to evaluate the potential clinical value of CTRP6 and CTRP9 in GDM. Methods: A total of 35 GDM subjects and 37 healthy controls, between 24 and 28 weeks of gestation, were included in the study. Diagnosis of GDM was made according to American Diabetes Association criteria. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of CTRP6 and CTRP9. Fasting insulin (FINS), IL-6, and TNF-α were detected by Luminex-xMAP technology. The main clinical characteristics, such as Anthropological data and metabolic parameters, were also obtained. Results: Circulating CTRP6, CTRP9, IL-6 and TNF-α were significantly elevated in GDM subjects compared with controls. Pearson correlation analysis showed that CTRP6 and CTRP9 were positively correlated with FPG (r = 0.280, P = 0.017 and r = 0.559, P &amp;lt; 0.001, respectively) and HOMA-IR (r = 0.250, P = 0.035 and r = 0.382, P = 0.001, respectively). Moreover, CTRP9 was also positively correlated with FINS (r = 0.253, P = 0.032), IL-6 (r = 0.283, P = 0.016) and TNF-α (r = 0.266, P = 0.024). The area under the receiver operating characteristic curve (AUC-ROC) indicated that the combination of CTRP6 and CTRP9 was more effective in predicting GDM than single indicators. Conclusion: Elevated CTRP6 and CTRP9 in GDM patients may be related to insulin resistance. And inflammatory factors may mediate the role of CTRP9 in insulin resistance. In addition, CTRP6 and CTRP9 may serve as candidate predictors in patients with early GDM. Disclosure Y.Liu: None. Y.Chen: None. W.Gu: None. L.Yin: None. H.Cao: None. M.Shi: None. Funding National Natural Science Foundation of China (81700723)

Association of solute carrier family 30 A8 zinc transporter gene variations with gestational diabetes mellitus risk in a Chinese population.

The solute carrier family 30 A8 zinc transporter (SLC30A8) plays a crucial role in insulin secretion. This study aimed to investigate the impact of SLC30A8 gene polymorphisms on gestational diabetes mellitus (GDM). The research objective was to select 500 patients with GDM and 502 control subjects. Rs13266634 and rs2466293 were genotyped using the SNPscan™ genotyping assay. Statistical tests, such as the chi-square test, t-test, logistic regression, ANOVA, and meta-analysis, were conducted to determine the differences in genotypes, alleles, and their associations with GDM risk. Statistically significant differences were observed in age, pregestational BMI, SBP, DBP, and parity between individuals with GDM and healthy subjects (P < 0.05). After adjusting for these factors, rs2466293 remained significantly associated with an increased risk of GDM in overall subjects (GG+AG vs. AA: OR = 1.310; 95% CI: 1.005-1.707; P = 0.046, GG vs. AA: OR = 1.523; 95% CI: 1.010-2.298; P = 0.045 and G vs. A: OR = 1.249; 95% CI: 1.029-1.516; P = 0.024). Rs13266634 was still found to be significantly associated with a decreased risk of GDM in individuals aged ≥ 30 years (TT vs. CT+CC: OR = 0.615; 95% CI: 0.392-0.966; P = 0.035, TT vs. CC: OR = 0.503; 95% CI: 0.294-0.861; P = 0.012 and T vs. C: OR =0.723; 95% CI: 0.557-0.937; P = 0.014). Additionally, the haplotype CG was found to be associated with a higher risk of GDM (P < 0.05). Furthermore, pregnant women with the CC or CT genotype of rs13266634 exhibited significantly higher mean blood glucose levels than those with the TT genotype (P < 0.05). Our findings were further validated by the results of a meta-analysis. The SLC30A8 rs2466293 polymorphism was found to be associated with an increased risk of GDM, while rs13266634 was associated with a decreased risk of GDM in individuals aged ≥ 30 years. These findings provide a theoretical basis for GDM testing.

Evaluating some haemostatic profiles and platelet aggregation in gestational diabetes mellitus subjects

Background: Hypercoagulability has been linked to an increase in risk factors, making diabetes a major cause of morbidity and mortality in low-income countries like Nigeria. This research examined some haemostatic parameters in women with gestational diabetes mellitus (GDM).Methodology: A total of 100 subjects consisting of 40 GDM, 30 non-gestational diabetes pregnant women (NGPW) attending the ante-natal clinic of the hospital and 30 women with neither diabetes nor pregnancy (NDNP) were enrolled as controls in this study. Ten milliliters of blood was collected and dispensed into an appropriate anticoagulant bottle. Prothrombin time (PT), Activated partial Thromboplastin Time (APTT), complete blood count (CBC) and fasting blood sugar (FBS) was estimated using standard techniques.Results: There was a significantly higher in the mean values of FBS, PT, APTT and WBC among GDM and NGPW when compared with NPNP (p&lt;0.05), while PCV was lower. FBS has positive correlation with PT and APTT while it shows negative correlation with platelet. APTT had a little edge over PT with higher area under the ROC curve of 0.997 than PT among GDM.Conclusion: In this study, women with GDM have considerably longer PT and APTT than NGPW and NDNP. Therefore, there may be possibility of haemorrhagic complications in gestational diabetes.

Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population.

MiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM). A total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level. There were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes. Our findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.

Exploring preconception signatures of metabolites in mothers with gestational diabetes mellitus using a non-targeted approach

BackgroundMetabolomic changes during pregnancy have been suggested to underlie the etiology of gestational diabetes mellitus (GDM). However, research on metabolites during preconception is lacking. Therefore, this study aimed to investigate distinctive metabolites during the preconception phase between GDM and non-GDM controls in a nested case–control study in Singapore.MethodsWithin a Singapore preconception cohort, we included 33 Chinese pregnant women diagnosed with GDM according to the IADPSG criteria between 24 and 28 weeks of gestation. We then matched them with 33 non-GDM Chinese women by age and pre-pregnancy body mass index (ppBMI) within the same cohort. We performed a non-targeted metabolomics approach using fasting serum samples collected within 12 months prior to conception. We used generalized linear mixed model to identify metabolites associated with GDM at preconception after adjusting for maternal age and ppBMI. After annotation and multiple testing, we explored the additional predictive value of novel signatures of preconception metabolites in terms of GDM diagnosis.ResultsA total of 57 metabolites were significantly associated with GDM, and eight phosphatidylethanolamines were annotated using HMDB. After multiple testing corrections and sensitivity analysis, phosphatidylethanolamines 36:4 (mean difference β: 0.07; 95% CI: 0.02, 0.11) and 38:6 (β: 0.06; 0.004, 0.11) remained significantly higher in GDM subjects, compared with non-GDM controls. With all preconception signals of phosphatidylethanolamines in addition to traditional risk factors (e.g., maternal age and ppBMI), the predictive value measured by area under the curve (AUC) increased from 0.620 to 0.843.ConclusionsOur data identified distinctive signatures of GDM-associated preconception phosphatidylethanolamines, which is of potential value to understand the etiology of GDM as early as in the preconception phase. Future studies with larger sample sizes among alternative populations are warranted to validate the associations of these signatures of metabolites and their predictive value in GDM.

Predictability of gestational diabetes mellitus using first trimester Serum uric acid levels

Introduction: For both mothers and fetuses, gestational diabetes mellitus (GDM) causes major morbidity and mortality in the Indian population. In pregnancy, serum uric acid levels are higher. Elevated first-trimester uric acid levels can be used to predict GDM. Study Design: In 1055 plasma samples taken at a mean gestational age of 9 ±2.1 weeks, uric acid was determined. The three-hour glucose tolerance test used to identify GDM as the main outcome. Results: The percentage of GDM was significantly high among the higher age group with 19.2% among 30-35 years of age and 25.8% among 35-40 years of age. With almost 35% of cases, GDM was most prevalent in the obese category. Among 348 patients with a confirmed family background of diabetes mellitus, 19.5% of pregnant women developed GDM. Uric acid levels were found significantly higher among GDM subjects both in first and second trimesters than in non-GDM subjects. Additionally, both normal and GDM individuals, serum uric acid levels were observed to be significantly greater in the second trimester than the first. Conclusion: First trimester hyperuricemia is linked to a higher chance of developing GDM.

Proteomic Approaches in the Study of Placenta of Pregnancy Complicated by Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM), a glucose intolerance developing or first recognized during pregnancy, leads to a series of short- and long-term maternal and fetal complications, somehow related to placenta structural and functional changes. The focus and the objective of the present review are to discuss the results which can be obtained by different mass spectrometric approaches in the study of placenta protein profile. Thus, matrix-assisted laser desorption/ionization mass spectrometry (MALDI) has been applied on placenta omogenates before and after one-dimensional electrophoretic separation, followed by tryptic digestion. MALDI imaging was used for direct investigation on the placenta tissue (both maternal and fetal sides). The results showed that some differences among the absolute abundances of some proteins are present for placenta samples from GDM patients. The majority of investigations were carried out by two-dimensional electrophoresis (2DE) followed by LC-MS/MS or, directly by the label-free LC-MSE approach. It should be emphasized that all these techniques were showed differences in the protein expression between the placenta samples from healthy or GDM subjects. 2DE was also employed to separate and compare placental protein levels from GDM and the control groups: differentially expressed proteins between the two groups were identified by MALDI-TOF/TOF mass spectrometry and were further confirmed by Western blotting. The physiopathological significance of the obtained results are reported and discussed in this narrative review. The experimental data obtained until now show that the newest, mass spectrometric approaches can be considered a valid tool to investigate the possible changes of placenta in the presence of GDM.

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.

The Gut Mycobiome Characterization of Gestational Diabetes Mellitus and Its Association With Dietary Intervention.

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The active interface between gut microbiota and diet contributes to metabolic homeostasis in GDM. However, the contributions of gut mycobiome have been neglected. Here, we profiled the gut fungi between GDM and healthy subjects at two time points and investigate whether variations in gut mycobiome correlate with key features of host metabolism and diet management in this observational study. We identified that Hanseniaspora, Torulaspora, Auricularia, Alternaria, and Candida contributed to GDM patient clustering, indicating that these fungal taxa are associated with abnormal blood glucose levels, and the causality needs to be further explored. While Penicillium, Ganoderma, Fusarium, Chaetomium, and Heterobasidion had significant explanatory effects on healthy subject clustering. In addition, spearman analysis further indicated that blood glucose levels were negatively correlated with polysaccharide-producing genera, Ganoderma, which could be reshaped by the short-term diet. The Penicillium which was negatively correlates with metabolic parameters, also exhibited the antimicrobial attribute by the fungal-bacterial interaction analysis. These data suggest that host metabolic homeostasis in GDM may be influenced by variability in the mycobiome and could be reshaped by the diet intervention. This work reveals the potential significance of the gut mycobiome in health and has implications for the beneficial effects of diet intervention on host metabolic homeostasis through regulating gut fungal abundance and metabolites.

1059-P: Metabolic Trajectories from Preconception to Midpregnancy Using a Nontargeted Approach in Mothers with Gestational Diabetes Mellitus

The trajectories of plasma lipids and fatty acids from preconception to antenatal phases are understudied. Within a Singapore preconception and pregnancy cohort of 373 live singletons, we ascertained 35 Chinese pregnant women with gestational diabetes mellitus (GDM) according to IADPSG criteria between 24-28 weeks of gestation, and matched with 35 non-GDM Chinese controls by age and pre-pregnancy body mass index. We collected bloo samples at preconception, early (11-13 weeks) , and mid-pregnancy (18-21 weeks) . We employed OPLS-DA and logistic regression to discriminate women with and without GDM using a non-targeted approach. We applied a generalized linear mixed model in cubic spline with interaction with gestation weeks to look at metabolite trajectories across three timepoints between GDM and non-GDM matches. A total of metabolites exhibited distinctive signals from pregnant women with GDM from women without GDM in early pregnancy, such as LPE 22:6 and DHA: 22:6n3. All trajectories but one (palmitic acid) showed significant increments in preconception and mid-pregnancy phases, whereas a significant reduction in early pregnancy among GDM cases. Our data identified distinctive metabolites changes across preconception and mid-pregnancy phase among GDM subjects, and such novel findings might imply potential predictive values for incident GDM. Disclosure L.Li: None. X.Wang: None. L.Cui: None. C.Zhang: None. Spresto study group: n/a. Funding Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014; NMRC TA/0027/2014) .

Association Between Gut Microbiota and Insulin Therapy in Women With Gestational Diabetes Mellitus

ObjectivesAt the time of diagnosis, the blood glucose of women with gestational diabetes mellitus (GDM) who require subsequent insulin treatment does not differ from that of women with adequate diet control. Hence, in this study, we aimed to determine the role of maternal gut microbiota as a marker of insulin necessity in GDM and to identify the effect of insulin therapy on gut microbiota composition in mothers with GDM and their newborns. MethodsSeventy-one pregnant women were enrolled into the study, including 38 GDM and 33 non-GDM participants. During the follow-up period, 8 of the 38 GDM subjects required insulin therapy (GDM-I group), whereas 30 of the 38 GDM cases with sufficient glycemic control by diet alone (GDM-D group). Maternal blood and feces were obtained at the time of GDM diagnosis (pretreatment; 24 to 28 weeks of gestation) and before delivery (posttreatment; ≥37 weeks of gestation). Meconium and first feces of the newborns were also collected. ResultsPretreatment, the glycemic profile did not differ between the GDM-D and GDM-I groups. However, the proportions of Clostridiales, Lactobacillus and Bacteroidetes were higher in the GDM-I group than in the non-GDM and GDM-D groups. After treatment, gut microbiota composition showed no difference between non-GDM and GDM-I groups. Interestingly, a higher Firmicutes/Bacteroidetes (F/B) ratio was displayed in GDM-D mothers at posttreatment, and this was also observed in both meconium and first feces of GDM-D newborns. ConclusionInsulin therapy changed maternal gut microbiota composition, which could be transferable to the mothers’ newborns.

Neuregulin 4 (NRG4) – the hormone with clinical significance in gestational diabetes mellitus

This study aimed at determining the association between serum neuregulin 4 (NRG4) and insulin in gestational diabetes mellitus (GDM) and their correlation with other metabolic parameters. A cross-sectional study was conducted from June 2018 to February 2019 at Ziauddin University, Karachi. Pregnant women (n = 80), at 24–28 weeks of gestation, were recruited. Demographic data, anthropometric measurements and antenatal history were recorded. The fasting blood was drawn for testing fasting blood sugar (FBS), NRG4, insulin and lipid profile. The subjects were evaluated for glucose challenge test after 50 g glucose ingestion. NRG4 levels (1.00 ± 0.15) were found significantly high (p < .04) in healthy group compared to GDM (0.95 ± 0.11). In GDM females, high levels for FBS (p < .02) and cholesterol (p < .03) were observed. Homeostatic model assessment of insulin resistance (HOMA-IR) had direct weak association with NRG4, inverse relationship with cholesterol and LDL but significant association (p < .05) with insulin. Significantly high NRG4 in healthy females suggests its potential role in regulating insulin sensitivity. Impact Statement What is already known on this subject? Neuregulin 4 (NGR4) is a batokine which plays a potential role in regulating insulin sensitivity, maintaining energy and metabolic homeostasis. Due to its role in lipid and glucose homeostasis, some studies report its role in gestational diabetes mellitus (GDM) but the results were controversial. What do the results of this study add? The study showed that NGR4 levels were significantly low in GDM subjects. Other metabolic factors especially insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were found associated significantly (p < .05) with NGR4. What are the implications of these findings for clinical practice and/or further research? NGR4 can be a potential biomarker for gestational diabetes. Nevertheless, in order to confirm these findings, further studies, with bigger sample size are required to further ascertain the prospects of NRG4 as a potential biomarker for gestational diabetes.