Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors

BackgroundAbnormally changed steroid hormones during pregnancy are closely related to the pathological process of gestational diabetes mellitus (GDM). Our aim was to systematically profile the metabolic alteration of circulating steroid hormones in GDM women and screen for risk factors.MethodsThis s...

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Main Authors: Na Yang, Wei Zhang, Cheng Ji, Jiajia Ge, Xiaoli Zhang, Meijuan Li, Min Wang, Tianqi Zhang, Jun He, Huaijun Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1196935/full
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author Na Yang
Na Yang
Wei Zhang
Cheng Ji
Jiajia Ge
Xiaoli Zhang
Meijuan Li
Min Wang
Tianqi Zhang
Jun He
Huaijun Zhu
author_facet Na Yang
Na Yang
Wei Zhang
Cheng Ji
Jiajia Ge
Xiaoli Zhang
Meijuan Li
Min Wang
Tianqi Zhang
Jun He
Huaijun Zhu
author_sort Na Yang
collection DOAJ
description BackgroundAbnormally changed steroid hormones during pregnancy are closely related to the pathological process of gestational diabetes mellitus (GDM). Our aim was to systematically profile the metabolic alteration of circulating steroid hormones in GDM women and screen for risk factors.MethodsThis study was a case-control study with data measured from 40 GDM women and 70 healthy pregnant women during their 24-28 gestational weeks. 36 kinds of steroid hormones, including 3 kinds of corticosteroids, 2 kinds of progestins, 5 kinds of androgens and 26 kinds of downstream estrogens in serum were systematically measured using a combined sensitive UPLC-MS/MS method. The flux of different metabolic pathways of steroid hormones was analyzed. Logistic regression and ROC curve model analyses were performed to identify potential steroid markers closely associated with GDM development.ResultsSerum corticosteroids, progestins and almost all the estrogen metabolites via 16-pathway from parent estrogens were higher in GDM women compared with healthy controls. Most of the estrogen metabolites via 4-pathway and more than half of the metabolites via 2-pathway were not significantly different. 16α-hydroxyestrone (16OHE1), estrone-glucuronide/sulfate (E1-G/S) and the ratio of total 2-pathway estrogens to total estrogens were screened as three indicators closely related to the risk of GDM development. The adjusted odds ratios of GDM for the highest quartile compared with the lowest were 72.22 (95% CI 11.27-462.71, Ptrend<0.001) for 16OHE1 and 6.28 (95% CI 1.74-22.71, Ptrend<0.05) for E1-G/S. The ratio of 2-pathway estrogens to total estrogens was negatively associated with the risk of GDM.ConclusionThe whole metabolic flux from cholesterol to downstream steroid hormones increased in GDM condition. The most significant changes were observed in the 16-pathway metabolism of estrogens, rather than the 2- or 4-pathway or other types of steroid hormones. 16OHE1 may be a strong marker associated with the risk for GDM.
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spelling doaj.art-be8f9dee2aee43088a790c232bc8e1e92023-06-15T05:49:15ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-06-011410.3389/fendo.2023.11969351196935Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factorsNa Yang0Na Yang1Wei Zhang2Cheng Ji3Jiajia Ge4Xiaoli Zhang5Meijuan Li6Min Wang7Tianqi Zhang8Jun He9Huaijun Zhu10Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaNanjing Qlife Medical Technology Co., Ltd, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaNanjing Qlife Medical Technology Co., Ltd, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaBackgroundAbnormally changed steroid hormones during pregnancy are closely related to the pathological process of gestational diabetes mellitus (GDM). Our aim was to systematically profile the metabolic alteration of circulating steroid hormones in GDM women and screen for risk factors.MethodsThis study was a case-control study with data measured from 40 GDM women and 70 healthy pregnant women during their 24-28 gestational weeks. 36 kinds of steroid hormones, including 3 kinds of corticosteroids, 2 kinds of progestins, 5 kinds of androgens and 26 kinds of downstream estrogens in serum were systematically measured using a combined sensitive UPLC-MS/MS method. The flux of different metabolic pathways of steroid hormones was analyzed. Logistic regression and ROC curve model analyses were performed to identify potential steroid markers closely associated with GDM development.ResultsSerum corticosteroids, progestins and almost all the estrogen metabolites via 16-pathway from parent estrogens were higher in GDM women compared with healthy controls. Most of the estrogen metabolites via 4-pathway and more than half of the metabolites via 2-pathway were not significantly different. 16α-hydroxyestrone (16OHE1), estrone-glucuronide/sulfate (E1-G/S) and the ratio of total 2-pathway estrogens to total estrogens were screened as three indicators closely related to the risk of GDM development. The adjusted odds ratios of GDM for the highest quartile compared with the lowest were 72.22 (95% CI 11.27-462.71, Ptrend<0.001) for 16OHE1 and 6.28 (95% CI 1.74-22.71, Ptrend<0.05) for E1-G/S. The ratio of 2-pathway estrogens to total estrogens was negatively associated with the risk of GDM.ConclusionThe whole metabolic flux from cholesterol to downstream steroid hormones increased in GDM condition. The most significant changes were observed in the 16-pathway metabolism of estrogens, rather than the 2- or 4-pathway or other types of steroid hormones. 16OHE1 may be a strong marker associated with the risk for GDM.https://www.frontiersin.org/articles/10.3389/fendo.2023.1196935/fullsteroid hormonesgestational diabetesUPLC-MS/MSestrogenscorticosteroidsprogestins
spellingShingle Na Yang
Na Yang
Wei Zhang
Cheng Ji
Jiajia Ge
Xiaoli Zhang
Meijuan Li
Min Wang
Tianqi Zhang
Jun He
Huaijun Zhu
Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
Frontiers in Endocrinology
steroid hormones
gestational diabetes
UPLC-MS/MS
estrogens
corticosteroids
progestins
title Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
title_full Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
title_fullStr Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
title_full_unstemmed Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
title_short Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
title_sort metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors
topic steroid hormones
gestational diabetes
UPLC-MS/MS
estrogens
corticosteroids
progestins
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1196935/full
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