Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy

Abstract To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 80...

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Main Authors: Sho Tano, Tomomi Kotani, Tatsuo Inamura, Fumie Kinoshita, Kazuya Fuma, Seiko Matsuo, Masato Yoshihara, Kenji Imai, Shigeru Yoshida, Mamoru Yamashita, Yasuyuki Kishigami, Hidenori Oguchi, Hiroaki Kajiyama, Takafumi Ushida
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02965-1
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author Sho Tano
Tomomi Kotani
Tatsuo Inamura
Fumie Kinoshita
Kazuya Fuma
Seiko Matsuo
Masato Yoshihara
Kenji Imai
Shigeru Yoshida
Mamoru Yamashita
Yasuyuki Kishigami
Hidenori Oguchi
Hiroaki Kajiyama
Takafumi Ushida
author_facet Sho Tano
Tomomi Kotani
Tatsuo Inamura
Fumie Kinoshita
Kazuya Fuma
Seiko Matsuo
Masato Yoshihara
Kenji Imai
Shigeru Yoshida
Mamoru Yamashita
Yasuyuki Kishigami
Hidenori Oguchi
Hiroaki Kajiyama
Takafumi Ushida
author_sort Sho Tano
collection DOAJ
description Abstract To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 802 pregnancies across 14 facilities. Pregnancies with a 75 g-OGTT performed by 20 weeks of gestation were included. Structural equation modeling (SEM) was used to evaluate direct and indirect effects of body mass index (BMI), High-GV, and covariates (e.g., age, ART, primiparity) on LoHDP. Overweight/obese women had significantly higher rates of High-GV (26.1 vs. 16.4%, p = 0.001) and LoHDP (17.6 vs. 7.9%, p < 0.001) compared to non-overweight/obese women. SEM revealed that BMI influenced LoHDP through both direct and indirect pathways. BMI had a direct effect on LoHDP (β = 0.20, p < 0.01), and an indirect effect mediated by High-GV, with BMI significantly associated with High-GV (β = 0.15, p < 0.01), and High-GV positively associated with LoHDP (β = 0.12, p < 0.01). In Non-GDM pregnancies, High-GV showed an even stronger association with LoHDP (β = 0.25, p < 0.001). This study identifies High-GV as a key mediator linking pre-pregnancy overweight/obesity to LoHDP. These findings suggest that targeting glucose variability in early pregnancy could mitigate LoHDP risk, particularly in overweight/obese women, regardless of GDM status. Future preventive strategies should integrate multifaceted approaches addressing maternal BMI and glucose regulation to improve maternal and neonatal outcomes.
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spelling doaj-art-2e368609fa9d4170b2ed6747383177002025-08-20T02:34:06ZengNature PortfolioScientific Reports2045-23222025-05-0115111010.1038/s41598-025-02965-1Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancySho Tano0Tomomi Kotani1Tatsuo Inamura2Fumie Kinoshita3Kazuya Fuma4Seiko Matsuo5Masato Yoshihara6Kenji Imai7Shigeru Yoshida8Mamoru Yamashita9Yasuyuki Kishigami10Hidenori Oguchi11Hiroaki Kajiyama12Takafumi Ushida13Department of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Hamamatsu University School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineData Science Division, Data Coordinating Center, Department of Advanced Medicine, Nagoya University HospitalDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineKishokai Medical CorporationKishokai Medical CorporationDepartment of Obstetrics, Perinatal Medical Center, TOYOTA Memorial HospitalDepartment of Obstetrics, Perinatal Medical Center, TOYOTA Memorial HospitalDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineAbstract To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 802 pregnancies across 14 facilities. Pregnancies with a 75 g-OGTT performed by 20 weeks of gestation were included. Structural equation modeling (SEM) was used to evaluate direct and indirect effects of body mass index (BMI), High-GV, and covariates (e.g., age, ART, primiparity) on LoHDP. Overweight/obese women had significantly higher rates of High-GV (26.1 vs. 16.4%, p = 0.001) and LoHDP (17.6 vs. 7.9%, p < 0.001) compared to non-overweight/obese women. SEM revealed that BMI influenced LoHDP through both direct and indirect pathways. BMI had a direct effect on LoHDP (β = 0.20, p < 0.01), and an indirect effect mediated by High-GV, with BMI significantly associated with High-GV (β = 0.15, p < 0.01), and High-GV positively associated with LoHDP (β = 0.12, p < 0.01). In Non-GDM pregnancies, High-GV showed an even stronger association with LoHDP (β = 0.25, p < 0.001). This study identifies High-GV as a key mediator linking pre-pregnancy overweight/obesity to LoHDP. These findings suggest that targeting glucose variability in early pregnancy could mitigate LoHDP risk, particularly in overweight/obese women, regardless of GDM status. Future preventive strategies should integrate multifaceted approaches addressing maternal BMI and glucose regulation to improve maternal and neonatal outcomes.https://doi.org/10.1038/s41598-025-02965-1OverweightObesityGlucose fluctuationPreeclampsiaPreventive medicine
spellingShingle Sho Tano
Tomomi Kotani
Tatsuo Inamura
Fumie Kinoshita
Kazuya Fuma
Seiko Matsuo
Masato Yoshihara
Kenji Imai
Shigeru Yoshida
Mamoru Yamashita
Yasuyuki Kishigami
Hidenori Oguchi
Hiroaki Kajiyama
Takafumi Ushida
Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
Scientific Reports
Overweight
Obesity
Glucose fluctuation
Preeclampsia
Preventive medicine
title Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
title_full Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
title_fullStr Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
title_full_unstemmed Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
title_short Glucose variability as a key mediator in the relationship between pre-pregnancy overweight/obesity and late-onset hypertensive disorders of pregnancy
title_sort glucose variability as a key mediator in the relationship between pre pregnancy overweight obesity and late onset hypertensive disorders of pregnancy
topic Overweight
Obesity
Glucose fluctuation
Preeclampsia
Preventive medicine
url https://doi.org/10.1038/s41598-025-02965-1
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