{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:28:30Z","timestamp":1788791310001,"version":"build-2803163510"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Gestational diabetes mellitus (GDM) is a prevalent metabolic complication of pregnancy with rising global incidence. Its increasing prevalence parallels the rising rates of pre-pregnancy obesity worldwide. While physiological insulin resistance is a normal feature of pregnancy, excess maternal adiposity exacerbates this process and significantly increases the risk of GDM. Emerging evidence highlights immune dysregulation as a plausible mechanistic link between pre-pregnancy obesity and impaired metabolic adaptation during pregnancy. Obesity is characterised by chronic, low-grade inflammation, driven by adipose tissue expansion, immune cell infiltration, and dysregulated cytokine and adipokine production. These changes may collectively impair insulin signalling, disrupt placental function, and alter maternal\u2013foetal immune tolerance. In this review, we synthesise current understanding of the immunological pathways connecting pre-pregnancy obesity to GDM, including alterations in innate and adaptive immune responses, soluble inflammatory mediators, and placental immune dynamics. By integrating metabolic and immunological perspectives, this narrative mini-review highlights potential mechanisms underpinning obesity-associated GDM and highlights critical gaps in knowledge relevant to early risk stratification and targeted prevention strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1940789","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:46:01Z","timestamp":1788788761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune dysregulation linking pre-pregnancy obesity to gestational diabetes mellitus"],"prefix":"10.3389","volume":"17","author":[{"given":"Hanna Margrethe Storheil","family":"Skarstad","sequence":"first","affiliation":[{"name":"Department of Circulation and Medical Imaging, Norwegian University of Science and Technology","place":["Trondheim, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Abu Jafar","family":"Sujan","sequence":"additional","affiliation":[{"name":"Department of Circulation and Medical Imaging, Norwegian University of Science and Technology","place":["Trondheim, Norway"]},{"name":"Department of Women\u2019s Health, St. Olav\u2019s Hospital, Trondheim University Hospital","place":["Trondheim, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Moholdt","sequence":"additional","affiliation":[{"name":"Department of Circulation and Medical Imaging, Norwegian University of Science and Technology","place":["Trondheim, Norway"]},{"name":"Department of Medicine, St. Olav\u2019s Hopsital","place":["Trondheim, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Z.","family":"Zulu","sequence":"additional","affiliation":[{"name":"Department of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand","place":["Johannesburg, South Africa"]},{"name":"Institute for 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