Evidence of tissue specific alterations in inflammatory profiles in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as significant glucose intolerance first diagnosed in pregnancy. GDM develops due to exaggerated insulin resistance in pregnancy, mediated by insufficient pancreatic ß-cell compensation. Immune-metabolic interactions may equally be potential contributing factors by suppressing insulin signalling particularly in adipose tissue. In this study, we characterised immune cell populations and cytokine profiles locally in both visceral adipose and placental tissues and systemically in the maternal circulation in both GDM and normal glucose tolerant (NGT) participants at term. Circulating glucose and insulin levels were used to calculate homeostatic model assessment for insulin resistance (HOMA-IR) values. GDM participants had significantly higher fasting circulating insulin and HOMA-IR scores. While there was no significant difference in the frequency of immune cell populations at any site between study groups, there was a significant increase in mitochondrial-specific ROS production in placental macrophages in GDM. There was a significant increase in circulating concentrations of pro-inflammatory cytokines IL-6 (p=0.003), IL-17A (p=0.04), IL-12p70 (p=0.05) and MCP-1 (p=0.03) in GDM. While there was no significant difference in cytokine production in visceral adipose tissue between study groups, there was evidence of increased placental inflammation in GDM, with elevated IL-6 (p=0.028), TNF-α (p=0.008) and IL-18 (p=0.04). In GDM, circulating NKT and CD4+ and CD8+ T-cells negatively correlated with HOMA-IR, while there was a positive correlation with memory CD4 T-cells in visceral adipose tissue. Maternal inflammation may exacerbate maternal resistance during pregnancy but may equally represent a pathophysiological link between GDM and future maternal risk of cardiometabolic complications.