The expression of genes involved in NF-κB activation in peripheral blood mononuclear cells of patients with gestational diabetes

Objective: In patients with obesity and type 2 diabetes, the changes in insulin resistance are associated with the changes in expression of genes involved in nuclear factor-kappa B (NF-kappa B) activation in peripheral blood mononuclear cells (PBMCs). As such studies have never been carried out in patients with gestational diabetes (GDM), in this study, we evaluated the expression of genes involved in NF-kappa B activation and related to glucose metabolism in PBMCs obtained from pregnant women with GDM and normal glucose tolerance (NGT). Design and methods: RT-PCR was performed in 60 pregnant women divided into three groups: GDM at the 1st visit, i.e. in the 24th-28th weeks of gestation (GDM1), NGT at the first visit and GDM in the 29th-32nd weeks (GDM2), and NGT at both visits. The tests were repeated 3 months postpartum. Results: The GDM1 group had significantly higher TLR2 (P=0.024), TLR4 (P=0.037), STAT1 (P=0.027), and CX3CL1 (P=0.017) mRNA expression, whereas the GDM2 group showed markedly lower TNFRSF1A (P=0.042), PPARG (=0.018), STAT3 (P=0.013), and CX3CL1 (p=0.038) mRNA expression in comparison with the NGT group. The women with NGT at the 1st visit who later developed GDM had significantly higher fasting glucose (P=0.01), HOMA-IR (P=0.004), and TLR2 mRNA expression (P=0.04), as well as lower ISSI2 (P=0.01) and disposition indices, DI30 (P=0.03) and DI120 (P=0.01), than had the women who remained normoglycemic. Conclusions: Our results suggest that elevated TLR2 expression, as well as higher fasting glucose and lower compensation for increased insulin resistance, may represent early metabolic disturbances in the development of GDM. European Journal of Endocrinology 168 419-427