Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics

Objective: Women with gestational diabetes mellitus (GDM) often develop a metabolic memory that increases the risk of future metabolic disorders, even after blood glucose levels normalize following clinical intervention. However, the impact of this metabolic memory on susceptibility to SARS-CoV-2 re...

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Main Authors: Zhangyan Li, Qiuhan Lu, Rui Zhang, Nuerbiya Xilifu, Yue Li, Xinmei Huang, Jiaying Zhang, Shufei Zang, Guozhi Jiang, Jun Liu
Format: Article
Language:English
Published: Bioscientifica 2025-03-01
Series:Endocrine Connections
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Online Access:https://ec.bioscientifica.com/view/journals/ec/14/4/EC-24-0681.xml
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author Zhangyan Li
Qiuhan Lu
Rui Zhang
Nuerbiya Xilifu
Yue Li
Xinmei Huang
Jiaying Zhang
Shufei Zang
Guozhi Jiang
Jun Liu
author_facet Zhangyan Li
Qiuhan Lu
Rui Zhang
Nuerbiya Xilifu
Yue Li
Xinmei Huang
Jiaying Zhang
Shufei Zang
Guozhi Jiang
Jun Liu
author_sort Zhangyan Li
collection DOAJ
description Objective: Women with gestational diabetes mellitus (GDM) often develop a metabolic memory that increases the risk of future metabolic disorders, even after blood glucose levels normalize following clinical intervention. However, the impact of this metabolic memory on susceptibility to SARS-CoV-2 remains unclear. Therefore, we aim to investigate the potential association between metabolic memory in GDM and susceptibility to SARS-CoV-2 infection. Methods: We conducted a prospective cohort study with 1,675 pregnant women, including 197 (11.8%) with GDM. Postpartum SARS-CoV-2 infections were tracked via telephone follow-up and categorized into negative and positive groups. Logistic regression was used to explore risk factors for SARS-CoV-2 infection. Peripheral blood samples were collected from 30 GDM and 30 normal glucose-tolerant (NGT) pregnant women in three trimesters (T1, T2 and T3) for longitudinal untargeted metabolomics to identify GDM and SARS-CoV-2-associated metabolites. Limma package was applied to find differential expressed metabolites associated with SARS-CoV-2 infection and GDM. Results: Among 1,675 women, 1,348 (80.5%) tested positive for SARS-CoV-2. GDM postpartum women had higher SARS-CoV-2 infection rates (88.3 vs 79.4%, P = 0.003) than NGT women. GDM was associated with SARS-CoV-2 infection (T2: OR (95% CI): 2.17 (1.26–3.54), P = 0.005; T3: OR (95% CI): 1.70 (1.03–2.82), P = 0.040). Compared to the SARS-CoV-2 negative group, the positive group exhibited elevated levels of allantoic acid, LPE (0:0/22:6), LPC (15:0/0:0) and 1-linoleoyl-sn-glycero-3-phosphorylcholine in T1 and T2, before clinical intervention. In T3, allantoic acid remained elevated post-intervention. A similar increase as described above was observed in the GDM compared to the NGT group. The tricarboxylic acid cycle was the sole overlapping enriched pathway in the SARS-CoV-2 positive versus negative group and the GDM versus NGT group. Cis-aconitic acid, a metabolite from this pathway, was elevated in T3 in the GDM group. Conclusion: Compared to NGT, women with GDM are at a higher risk of postnatal SARS-CoV-2 infection. Metabolic memory from GDM may heighten susceptibility to SARS-CoV-2.
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spelling doaj-art-79c353ee63da4cd7b48676749ea9ae542025-08-20T02:55:58ZengBioscientificaEndocrine Connections2049-36142025-03-0114410.1530/EC-24-06811Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomicsZhangyan Li0Qiuhan Lu1Rui Zhang2Nuerbiya Xilifu3Yue Li4Xinmei Huang5Jiaying Zhang6Shufei Zang7Guozhi Jiang8Jun Liu9Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaObjective: Women with gestational diabetes mellitus (GDM) often develop a metabolic memory that increases the risk of future metabolic disorders, even after blood glucose levels normalize following clinical intervention. However, the impact of this metabolic memory on susceptibility to SARS-CoV-2 remains unclear. Therefore, we aim to investigate the potential association between metabolic memory in GDM and susceptibility to SARS-CoV-2 infection. Methods: We conducted a prospective cohort study with 1,675 pregnant women, including 197 (11.8%) with GDM. Postpartum SARS-CoV-2 infections were tracked via telephone follow-up and categorized into negative and positive groups. Logistic regression was used to explore risk factors for SARS-CoV-2 infection. Peripheral blood samples were collected from 30 GDM and 30 normal glucose-tolerant (NGT) pregnant women in three trimesters (T1, T2 and T3) for longitudinal untargeted metabolomics to identify GDM and SARS-CoV-2-associated metabolites. Limma package was applied to find differential expressed metabolites associated with SARS-CoV-2 infection and GDM. Results: Among 1,675 women, 1,348 (80.5%) tested positive for SARS-CoV-2. GDM postpartum women had higher SARS-CoV-2 infection rates (88.3 vs 79.4%, P = 0.003) than NGT women. GDM was associated with SARS-CoV-2 infection (T2: OR (95% CI): 2.17 (1.26–3.54), P = 0.005; T3: OR (95% CI): 1.70 (1.03–2.82), P = 0.040). Compared to the SARS-CoV-2 negative group, the positive group exhibited elevated levels of allantoic acid, LPE (0:0/22:6), LPC (15:0/0:0) and 1-linoleoyl-sn-glycero-3-phosphorylcholine in T1 and T2, before clinical intervention. In T3, allantoic acid remained elevated post-intervention. A similar increase as described above was observed in the GDM compared to the NGT group. The tricarboxylic acid cycle was the sole overlapping enriched pathway in the SARS-CoV-2 positive versus negative group and the GDM versus NGT group. Cis-aconitic acid, a metabolite from this pathway, was elevated in T3 in the GDM group. Conclusion: Compared to NGT, women with GDM are at a higher risk of postnatal SARS-CoV-2 infection. Metabolic memory from GDM may heighten susceptibility to SARS-CoV-2.https://ec.bioscientifica.com/view/journals/ec/14/4/EC-24-0681.xmlgestational diabetes mellitussars-cov-2metabolic memorysusceptibility
spellingShingle Zhangyan Li
Qiuhan Lu
Rui Zhang
Nuerbiya Xilifu
Yue Li
Xinmei Huang
Jiaying Zhang
Shufei Zang
Guozhi Jiang
Jun Liu
Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
Endocrine Connections
gestational diabetes mellitus
sars-cov-2
metabolic memory
susceptibility
title Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
title_full Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
title_fullStr Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
title_full_unstemmed Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
title_short Metabolic memory in gestational diabetes enhances SARS-CoV-2 susceptibility in postpartum women: a prospective cohort study integrated with longitudinal metabolomics
title_sort metabolic memory in gestational diabetes enhances sars cov 2 susceptibility in postpartum women a prospective cohort study integrated with longitudinal metabolomics
topic gestational diabetes mellitus
sars-cov-2
metabolic memory
susceptibility
url https://ec.bioscientifica.com/view/journals/ec/14/4/EC-24-0681.xml
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