Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus

AbstractWe aimed to identify serum metabolites related to abnormal glucose metabolism (AGM) among women with gestational diabetes mellitus (GDM). The study recruited 50 women diagnosed with GDM during mid-late pregnancy and 50 non-GDM matchees in a Singapore birth cohort. At the 5-year post-partum follow-up, we applied an untargeted approach to investigate the profiles of serum metabolites among all participants. We first employed OPLS-DA and logistic regression to discriminate women with and without follow-up AGM, and then applied area under the curve (AUC) to assess the incremental indicative value of metabolic signatures on AGM. We identified 23 candidate metabolites that were associated with postpartum AGM among all participants. We then narrowed down to five metabolites [p-cresol sulfate, linoleic acid, glycocholic acid, lysoPC(16:1) and lysoPC(20:3)] specifically associating with both GDM and postpartum AGM. The combined metabolites in addition to traditional risks showed a higher indicative value in AUC (0.92–0.94 vs. 0.74 of traditional risks and 0.77 of baseline diagnostic biomarkers) and R2 (0.67–0.70 vs. 0.25 of traditional risks and 0.32 of baseline diagnostic biomarkers) in terms of AGM indication, compared with the traditional risks model and traditional risks and diagnostic biomarkers combined model. These metabolic signatures significantly increased the AUC value of AGM indication in addition to traditional risks, and might shed light on the pathophysiology underlying the transition from GDM to AGM.

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A longitudinal study of thyroid markers during pregnancy and the risk of gestational diabetes mellitus and post‐partum glucose metabolism

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.3441 ◽

2021 ◽

Author(s):

Lei Tang ◽

Ping Li ◽

Hua Zhou ◽

Ling Li

Keyword(s):

Diabetes Mellitus ◽

Longitudinal Study ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Post Partum

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Long Term Predictors of Post-Partum Glucose Metabolism in Women with Gestational Diabetes Mellitus

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0030-1249634 ◽

2010 ◽

Vol 118 (08) ◽

pp. 485-489 ◽

Cited By ~ 4

Author(s):

G. Seghieri ◽

F. Tesi ◽

A. De Bellis ◽

R. Anichini ◽

G. Fabbri ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Post Partum

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Functional Defects of Regulatory T Cell Through Interleukin 10 Mediated Mechanism in the Induction of Gestational Diabetes Mellitus

DNA and Cell Biology ◽

10.1089/dna.2017.4005 ◽

2018 ◽

Vol 37 (3) ◽

pp. 278-285 ◽

Cited By ~ 8

Author(s):

Yan Yang ◽

lixiu Liu ◽

Beibei Liu ◽

Qi Li ◽

Zhe Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

T Cell ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Regulatory T Cell ◽

Interleukin 10 ◽

Functional Defects

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Maternal Metabolites Associated with Gestational Diabetes Mellitus and a Postpartum Disorder of Glucose Metabolism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab513 ◽

2021 ◽

Author(s):

Yu Liu ◽

Alan Kuang ◽

James R Bain ◽

Michael J Muehlbauer ◽

Olga R Ilkayeva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Adverse Pregnancy Outcome ◽

Model Assessment ◽

Glucose Load ◽

Serum Samples ◽

Metabolic Traits ◽

Postpartum Disorders

Abstract Objective To identify circulating metabolites present at ~28 weeks’ gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10-14 years later. Methods Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hr serum samples following a 75g glucose load at ∼28 weeks’ gestation from 2,290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Postpartum metabolic traits included fasting and 2-hr plasma glucose following a 75g glucose load, insulin resistance estimated by homeostasis model assessment, and disorders of glucose metabolism (prediabetes and type 2 diabetes) during the HAPO Follow-Up Study. Results Per-metabolite analyses identified numerous metabolites, ranging from amino acids and carbohydrates to fatty acids and lipids, before and 1-hr after a glucose load that were associated with GDM as well as development of a disorder of glucose metabolism and metabolic traits 10-14 years postpartum. A core group of fasting and 1-hr metabolites mediated, in part, the relationship between GDM and postpartum disorders of glucose metabolism, with the fasting and 1-hr metabolites accounting for 15.7% (7.1%-30.8%) and 35.4% (14.3%-101.0%) of the total effect size, respectively. For prediction of a postpartum disorder of glucose metabolism, addition of circulating fasting or 1-hr metabolites at ~28 weeks’ gestation showed little improvement in prediction performance compared to clinical factors alone. Conclusions The results demonstrate association of multiple metabolites with GDM and postpartum metabolic traits and begin to define the underlying pathophysiology of the transition from GDM to a postpartum disorder of glucose metabolism.

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Predictors of Insulin Treatment During Pregnancy and Abnormal Postpartum Glucose Metabolism in Patients with Gestational Diabetes Mellitus

Diabetes Metabolic Syndrome and Obesity Targets and Therapy ◽

10.2147/dmso.s233554 ◽

2019 ◽

Vol Volume 12 ◽

pp. 2655-2665 ◽

Cited By ~ 1

Author(s):

Lei Tang ◽

Shiting Xu ◽

Ping Li ◽

Ling Li

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Insulin Treatment

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Epigenetic Profiles Reveal That ADCYAP1 Serves as Key Molecule in Gestational Diabetes Mellitus

Computational and Mathematical Methods in Medicine ◽

10.1155/2019/6936175 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Xue Li ◽

Wenhong Yang ◽

Yanning Fang

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Principal Component ◽

Functional Principal Component Analysis ◽

Abnormal Glucose Metabolism ◽

Functional Principal Component ◽

Differentially Methylated Genes ◽

Normal Glucose

Gestational diabetes mellitus (GDM) refers to the condition which shows abnormal glucose metabolism that occurs during pregnancy, while normal glucose metabolism before pregnancy. In the present study, a novel analytical procedure was used to explore the key molecule of gestational diabetes mellitus. First, the weighted pathway model was carried out subsequently to eliminate the gene-overlapping effects among pathways. Second, we assessed the enriched pathways by a combination of Fisher’s t-test and the Mann–Whitney U test. We carried out the functional principal component analysis by estimating F values of genes to identify the hub genes in the enriched pathways. Results showed that a total of 4 differential pathways were enriched. The key pathway was considered as the insulin secretion pathway. F values of each gene in the key pathway were calculated. Three hub molecules were identified as hub differentially methylated genes, namely, CAMK2B, ADCYAP1, and KCNN2. In addition, by further comparing the gene expression data in a validation cohort, one key molecule was obtained, ADCYAP1. Therefore, ADCYAP1 may serve as a potential target for the treatment of GDM.

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