(1174) Placental Inflammation is More Common in A2 versus A1 Gestational Diabetes

It is well-known that worse obstetric outcomes are observed in pregnancies complicated by A2 compared to A1 gestational diabetes mellitus (GDM). Insulin resistance is thought to exaggerate placental immune responses. We hypothesize that there is greater placental inflammation in patients with A2GDM compared to A1GDM. Inflammatory responses in the placenta are mediated, in part, by macrophages (aka Hofbauer cells). To test our hypothesis, we compared macrophage abundance and proinflammatory gene expression in placentas from patients with A2GDM versus A1GDM.

Study Design:

Intervillous placental biopsies were collected and analyzed from term, unlabored patients delivered by planned cesarean. Insulin was the sole treatment modality for all A2GDM patients in this analysis. Histological analysis by CD163 staining was conducted to quantify the number of macrophages. The expression of 732 macrophage-related genes were compared between placentas from pregnancies complicated by A2GDM versus A1GDM (n=12/condition). Gene expression was also referenced to uncomplicated pregnancies using the NanoString nCounter system.

Results:

The number of macrophages (CD163+ cells) did not differ between A2GDM and A1GDM (Figure 1.A). However, in placentas from patients with A2GDM, 47 genes were significantly upregulated, and 3 downregulated when compared to those with A1GDM (Figure 1.B). The most significantly upregulated genes promote macrophage inflammation, including LTB4, CD160 and IRF5.

Conclusion:

While that the number of macrophages did not differ between groups, significant upregulation of macrophage associated inflammatory genes was observed in placentas from patients with A2GDM. Placental inflammation is thought to contribute to adverse obstetric outcomes such as preeclampsia. Further research is warranted to evaluate if placental inflammation is associated with specific adverse outcomes observed in GDM.