Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus

IntroductionWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing prediabetes or type 2 diabetes later in life. Recent studies have highlighted the regulation and function of innate lymphoid cells (ILCs) in metabolic homeostasis. However, the multifactorial impac...

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Main Authors: Julia Sbierski-Kind, Stephan Schlickeiser, Lorenzo Semeia, Saori Harada, Eleni Pappa, Javier Villamizar Cujar, Minh-Thuy Katschke, Christina Gar, Andreas Lechner, Andreas L. Birkenfeld, Uta Ferrari, Jochen Seissler
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Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559326/full
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author Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Stephan Schlickeiser
Stephan Schlickeiser
Lorenzo Semeia
Lorenzo Semeia
Saori Harada
Saori Harada
Eleni Pappa
Eleni Pappa
Javier Villamizar Cujar
Minh-Thuy Katschke
Minh-Thuy Katschke
Christina Gar
Andreas Lechner
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Uta Ferrari
Uta Ferrari
Jochen Seissler
Jochen Seissler
author_facet Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Stephan Schlickeiser
Stephan Schlickeiser
Lorenzo Semeia
Lorenzo Semeia
Saori Harada
Saori Harada
Eleni Pappa
Eleni Pappa
Javier Villamizar Cujar
Minh-Thuy Katschke
Minh-Thuy Katschke
Christina Gar
Andreas Lechner
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Uta Ferrari
Uta Ferrari
Jochen Seissler
Jochen Seissler
author_sort Julia Sbierski-Kind
collection DOAJ
description IntroductionWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing prediabetes or type 2 diabetes later in life. Recent studies have highlighted the regulation and function of innate lymphoid cells (ILCs) in metabolic homeostasis. However, the multifactorial impact of both overweight/obesity and GDM on the immunological profile of circulating ILCs and the progression to prediabetes are not yet fully elucidated.MethodsBlood samples from 42 women with a history of insulin-treated GDM (GDMi), 33 women with a history of GDM without insulin treatment during pregnancy (GDM), and 45 women after a normoglycemic pregnancy (Ctrl) participating in the ongoing observational PPSDiab study were analyzed by flow cytometry for markers of ILC subsets at the baseline visit (3-16 months postpartum; Visit 1) and 5 years postpartum (58-66 months postpartum; Visit 2).ResultsDuring the first 5 years postpartum, 18 women of the GDMi group (42.8%), 10 women of the GDM group (30.3%), and 8 participants of the Ctrl group (17.8%) developed prediabetes, respectively. Total circulating type 1 innate lymphoid cells (ILC1s) and NK cell numbers as well as percent HLA-DR+ ILC1s were increased in GDMi versus GDM and Ctrl women both at the baseline visit and the 5-year follow-up. Although ILC subsets at Visit 1 could not predict the progression from GDM to prediabetes, ILC2 frequency was associated with insulin sensitivity index (ISI), whereas percent HLA-DR+ ILC1s were inversely correlated. Moreover, circulating leukocytes and total NK cells were associated with waist circumference and fat mass both at Visit 1 and Visit 2.DiscussionOur findings introduce human ILCs as a potential therapeutic target deserving further exploration.Trial registrationStudy ID 300-11.
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spelling doaj-art-7a67be23b9d74e2a9e632f90affb0b2f2025-08-20T02:47:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15593261559326Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitusJulia Sbierski-Kind0Julia Sbierski-Kind1Julia Sbierski-Kind2Julia Sbierski-Kind3Stephan Schlickeiser4Stephan Schlickeiser5Lorenzo Semeia6Lorenzo Semeia7Saori Harada8Saori Harada9Eleni Pappa10Eleni Pappa11Javier Villamizar Cujar12Minh-Thuy Katschke13Minh-Thuy Katschke14Christina Gar15Andreas Lechner16Andreas L. Birkenfeld17Andreas L. Birkenfeld18Andreas L. Birkenfeld19Uta Ferrari20Uta Ferrari21Jochen Seissler22Jochen Seissler23Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDivision of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, University Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, GermanyThe M3 Research Center, Medical Faculty, University Clinic Tübingen (UKT), Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Berlin, GermanyBerlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, GermanyIDM/fMEG Center of the Helmholtz Center Munich at the University of Tübingen, University of Tübingen, German Center for Diabetes Research (DZD), Tübingen, GermanyGraduate Training Centre of Neuroscience, International Max Planck Research School, University of Tübingen, Tübingen, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyInstitute for Medical Information Processing, Biometry and Epidemiology (IBE), Faculty of Medicine, LMU Munich, Pettenkofer School of Public Health, Munich, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany0German Center for Diabetes Research (DZD), Neuherberg, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDivision of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, University Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, GermanyThe M3 Research Center, Medical Faculty, University Clinic Tübingen (UKT), Tübingen, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDivision of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, University Hospital, Eberhard-Karls-Universität Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany0German Center for Diabetes Research (DZD), Neuherberg, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany0German Center for Diabetes Research (DZD), Neuherberg, GermanyDepartment of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany0German Center for Diabetes Research (DZD), Neuherberg, GermanyIntroductionWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing prediabetes or type 2 diabetes later in life. Recent studies have highlighted the regulation and function of innate lymphoid cells (ILCs) in metabolic homeostasis. However, the multifactorial impact of both overweight/obesity and GDM on the immunological profile of circulating ILCs and the progression to prediabetes are not yet fully elucidated.MethodsBlood samples from 42 women with a history of insulin-treated GDM (GDMi), 33 women with a history of GDM without insulin treatment during pregnancy (GDM), and 45 women after a normoglycemic pregnancy (Ctrl) participating in the ongoing observational PPSDiab study were analyzed by flow cytometry for markers of ILC subsets at the baseline visit (3-16 months postpartum; Visit 1) and 5 years postpartum (58-66 months postpartum; Visit 2).ResultsDuring the first 5 years postpartum, 18 women of the GDMi group (42.8%), 10 women of the GDM group (30.3%), and 8 participants of the Ctrl group (17.8%) developed prediabetes, respectively. Total circulating type 1 innate lymphoid cells (ILC1s) and NK cell numbers as well as percent HLA-DR+ ILC1s were increased in GDMi versus GDM and Ctrl women both at the baseline visit and the 5-year follow-up. Although ILC subsets at Visit 1 could not predict the progression from GDM to prediabetes, ILC2 frequency was associated with insulin sensitivity index (ISI), whereas percent HLA-DR+ ILC1s were inversely correlated. Moreover, circulating leukocytes and total NK cells were associated with waist circumference and fat mass both at Visit 1 and Visit 2.DiscussionOur findings introduce human ILCs as a potential therapeutic target deserving further exploration.Trial registrationStudy ID 300-11.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559326/fullinnate lymphoid cellsimmune activationinsulin resistancegestational diabetesprediabetes
spellingShingle Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Julia Sbierski-Kind
Stephan Schlickeiser
Stephan Schlickeiser
Lorenzo Semeia
Lorenzo Semeia
Saori Harada
Saori Harada
Eleni Pappa
Eleni Pappa
Javier Villamizar Cujar
Minh-Thuy Katschke
Minh-Thuy Katschke
Christina Gar
Andreas Lechner
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Andreas L. Birkenfeld
Uta Ferrari
Uta Ferrari
Jochen Seissler
Jochen Seissler
Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
Frontiers in Immunology
innate lymphoid cells
immune activation
insulin resistance
gestational diabetes
prediabetes
title Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
title_full Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
title_fullStr Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
title_full_unstemmed Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
title_short Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
title_sort association of overweight obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus
topic innate lymphoid cells
immune activation
insulin resistance
gestational diabetes
prediabetes
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559326/full
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