Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM

Abstract Background Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. Methods We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. Results Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001). Conclusion Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

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Circulating Exosomal hsa_circRNA_0039480 is Highly Expressed in Gestational Diabetes Mellitus and May Be Served As A Biomarker for Early Diagnosis of GDM

10.21203/rs.3.rs-813512/v1 ◽

2021 ◽

Author(s):

Bao Jiang ◽

Junfeng Zhang ◽

Xiubin Sun ◽

Chunyan Yang ◽

Guanghui Cheng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Expression Profiles ◽

Pearson Correlation ◽

First Trimester ◽

Circular Rna ◽

Diagnostic Value ◽

Pathological Process ◽

Pcr Analysis

Abstract Background: Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM.Methods: We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 hours before and 48 hours after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and circRNA-OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages.Results: Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery(P<0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P<0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r =0.496, P=0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P=0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P= 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC=0.754, P < 0.001).Conclusion: Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients and may be served as a candidate biomarker for early detection of GDM.

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Circular RNA expression profiles in umbilical cord blood exosomes from normal and gestational diabetes mellitus patients

Bioscience Reports ◽

10.1042/bsr20201946 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Minkai Cao ◽

Le Zhang ◽

Yu Lin ◽

Zhengying Li ◽

Jianjuan Xu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Expression Profiles ◽

Circular Rna ◽

Cellular Functions ◽

Pathway Analyses

Abstract Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circRNAs have been identified for their enrichment and stability in exosomes. However, the roles of circRNAs from umbilical cord blood exosomes in gestational diabetes mellitus (GDM) occurrence and fetus growth remains poorly understood. In the present study, we used microarray technology to construct a comparative circRNA profiling of umbilical cord blood exosomes between GDM patients and controls. We found the exosome particle size was larger, and the exosome concentration was higher in the GDM patients. A total of 88,371 circRNAs in umbilical cord blood exosomes from two groups were evaluated. Of these, 229 circRNAs were significantly up-regulated and 278 circRNAs were significantly down-regulated in the GDM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that circRNA parental genes involved in the regulation of metabolic process, growth and development were significantly enriched, which are important in GDM development and fetus growth. Further circRNA/miRNA interactions analysis showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with GDM. Collectively, these results lay a foundation for extensive studies on the role of exosomal circRNAs in GDM development and fetus growth.

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Circular RNA expression profiles in placental villi from women with gestational diabetes mellitus

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.03.051 ◽

2018 ◽

Vol 498 (4) ◽

pp. 743-750 ◽

Cited By ~ 25

Author(s):

Linping Yan ◽

Jie Feng ◽

Feng Cheng ◽

Xianwei Cui ◽

Lingjuan Gao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Expression Profiles ◽

Circular Rna ◽

Rna Expression ◽

Placental Villi

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The role of circular RNA circ_0008285 in gestational diabetes mellitus by regulating the biological functions of trophoblasts

Biological Research ◽

10.1186/s40659-021-00337-3 ◽

2021 ◽

Vol 54 (1) ◽

Author(s):

Haitian Chen ◽

Shaofeng Zhang ◽

Yanxin Wu ◽

Zhuyu Li ◽

Dongyu Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

High Throughput Sequencing ◽

Expression Profiles ◽

Circular Rna ◽

Circular Rnas ◽

Invasion And Migration ◽

And Migration

Abstract Background Circular RNAs (circRNAs) has emerged as vital regulator involved in various diseases. In this study, we identified and investigated the potential circRNAs involved in gestational diabetes mellitus (GDM). Methods High-throughput sequencing was used to collect the plasma circRNAs expression profiles of GDM patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expressions of circ_0008285 and circ_0001173 in the plasma specimens. The Pearson’s correlation test was employed to assess the correlation between 2 circRNAs expression and the clinicopathologic data. Two circRNAs expression was verified in high glucose (HG)-induced HTR-8/SVneo cells. MTS, transwell assay was used to evaluate the effects of circ_0008285 expression on HG-induced HTR-8/SVneo cells. The network of circ_0008285 was constructed using cytocape. Results In GDM patients, the expression of circ_0008285 was significantly upregulated, while that of circ_0001173 was decreased. Circ_0008285 was significantly correlated with the total cholesterol and LDL-C levels. Circ_0001173 was significantly correlated with glycated hemoglobin. HG promoted the proliferation, invasion, and migration in HTR-8/SVneo cells, while the knockdown of circ_0008285 exerted reverse effects. In addition, network construction exhibited that circ_0008285 had 45 miRNA binding sites, which correlated with 444 mRNA. Conclusions circ_0008285 plays an important role and provides a clue for the usage of therapeutic targets in the development of GDM.

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Association of First-Trimester Fasting Plasma Glucose with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes

Diabetes ◽

10.2337/db18-1448-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1448-P

Author(s):

PING LI ◽

SHUO LIN ◽

LING LI ◽

JINHUI CUI ◽

JIANHUI FAN

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Pregnancy Outcomes ◽

First Trimester ◽

Adverse Pregnancy Outcomes ◽

Fasting Plasma ◽

Adverse Pregnancy

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86-LB: Elevated First-Trimester Neutrophil Count Is Associated with the Development of Gestational Diabetes Mellitus in Pregnant Women

Diabetes ◽

10.2337/db19-86-lb ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 86-LB

Author(s):

TIANGE SUN ◽

FANHUA MENG ◽

RUI ZHANG ◽

ZHIYAN YU ◽

SHUFEI ZANG ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Neutrophil Count ◽

First Trimester

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1351-P: Association of Muscle/Fat Mass Ratio in the First Trimester with Gestational Diabetes Mellitus in Chinese Subjects

Diabetes ◽

10.2337/db20-1351-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1351-P

Author(s):

PING LI ◽

SHUO LIN ◽

JIANHUI FAN ◽

LONGYI ZENG

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fat Mass ◽

First Trimester ◽

Mass Ratio ◽

Chinese Subjects ◽

Fat Mass Ratio

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Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study

Nutrition & Metabolism ◽

10.1186/s12986-019-0425-9 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Chuyao Jin ◽

Lizi Lin ◽

Na Han ◽

Zhiling Zhao ◽

Zheng Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Binding Protein ◽

First Trimester ◽

Retinol Binding Protein ◽

Second Trimester ◽

Retinol Binding Protein 4 ◽

Plasma Retinol

Abstract Background To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester. Conclusions Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.

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