Abstract
Introduction: Gestational diabetes mellitus (GDM) is a major health concern during pregnancy, affecting both the mother and the baby. Immune system alterations, particularly changes in lymphocyte subsets and cytokine profiles, have been associated with the pathophysiology of various metabolic disorders, including diabetes. This study is aimed at systematically reviewing the literature on the changes in lymphocyte subsets and cytokines in GDM. Methods: In this systematic review, we applied specific criteria to select observational studies (such as case-controls, cross-sectionals, or cohorts) that focused on pregnant women. We performed an extensive search across electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar, from January 1, 2010, to March 20, 2024. Results: A total of 19 articles, with 2517 participants (1128 with GDM and 1389 without GDM), were included in the qualitative synthesis. Due to high heterogeneity among the articles, a meta-analysis was not conducted. The studies assessed 35 different lymphocyte subsets or proportions. The most commonly assessed subsets were CD3+ T cell (five articles, mostly no difference between GDM and non-GDM), CD4+ T cell (five articles with contradictory results), CD8+ T cell (four articles with contradictory results), B cell and NK cell (three articles, mostly no difference between GDM and non-GDM), and Tregs (three articles with contradictory results). Additionally, 32 cytokines or proportions were assessed in the studies. The most commonly assessed cytokines were IL-6 (eight articles, higher or similar levels in GDM compared to non-GDM), TNF-α (seven articles, mostly higher or similar levels in GDM compared to non-GDM), IL-10 (six articles, mostly no difference between GDM and non-GDM), IL-2 (three articles, mostly no difference between GDM and non-GDM), and IFN-γ (three articles with contradictory results). Conclusion: According to the results, there were no significant changes in CD3+ T cells, B cells, NK cells, IL-10, and IL-2 in GDM. However, the levels of IL-6 and TNF-α were higher or similar in GDM compared to non-GDM. The changes of other lymphocyte subsets and cytokines in GDM remained unclear.