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Sbierski-Kind, J. ; Schlickeiser, S.* ; Semeia, L. ; Harada, S.* ; Pappa, E.* ; Cujar, J.V.* ; Katschke, M.T.* ; Gar, C.* ; Lechner, A.* ; Birkenfeld, A.L. ; Ferrari, U.* ; Seissler, J.*

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

Front. Immunol. 16:1559326 (2025)

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INTRODUCTION: Women 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. METHODS: Blood 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). RESULTS: During 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. DISCUSSION: Our findings introduce human ILCs as a potential therapeutic target deserving further exploration. TRIAL REGISTRATION: Study ID 300-11.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Gestational Diabetes ; Immune Activation ; Innate Lymphoid Cells ; Insulin Resistance ; Prediabetes; Inflammation; Eosinophils; Obesity; Health; Risk

ISSN (print) / ISBN 1664-3224

e-ISSN 1664-3224

Journal Frontiers in Immunology

Quellenangaben Volume: 16, Article Number: 1559326

Publisher Frontiers

Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants Federal Ministry of Education and Research (BMBF)
German Center for Diabetes Research (DZD)
German Research Foundation (DFG, Deutsche Forschungsgemeinschaft)
German Diabetes Society
(Deutsche Diabetes Gesellschaft)
FoeFoLe, LMU Munich
German Society of Internal Medicine
(Deutsche Gesellschaft fr Innere Medizin, Clinician Scientist Program)
International Max Planck Research School for the Mechanisms of Mental Function and Dysfunction (IMPRS-MMFD)
Add-on Fellowship of the Joachim Herz Foundation
Helmholtz Zentrum Muenchen, Klinikum der Universitaet Muenchen