Immune dysregulation linking pre-pregnancy obesity to gestational diabetes mellitus

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-foetal 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.