Exposure to Gestational Diabetes Mellitus increases subclinical inflammation mediated in part by obesity.

Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focusing on elucidating the roles of obesity and GDM to the clinical outcome. Using immunoassays and multicolour flow cytometry, cytokine profiles and immune cell frequencies were measured in maternal circulation and central metabolic tissues (placenta and visceral adipose tissue (VAT)) in GDM-diagnosed (n=28) and normal glucose tolerant (n=32) women undergoing caesarean section. Participants were sub grouped as non-obese (BMI <30 kg/m2) or obese (BMI ≥30 kg/m2). Unsupervised data analysis was performed on the flow cytometry data set to identify functional alterations. GDM-obese participants had significantly elevated circulating IL-6 and IL-17A levels. GDM-nonobese participants had elevated circulating IL-12p70, elevated placental IL-17A and VAT IFN- γ production. Unsupervised clustering of immune populations across the three biological sites simultaneously, identified different NK and T-cell phenotypes that were altered in NGT-obese and GDM nonobese participants, while a classical tissue monocyte cluster were increased in GDM-obese participants. In this study, there was significant evidence of subclinical inflammation, and significant alterations in clusters of NK cells, T-cells and tissue monocyte populations in GDM. While increased adiposity assimilates with increased inflammation in the non-pregnant state, this overt relationship may not be as evident during pregnancy and warrants further examination in future longitudinal studies.