Endocrine Abstracts

Background: Gestational diabetes mellitus (GDM) is known to predispose offspring to metabolic diseases. However, the underlying mechanisms has not been thoroughly studied yet. The glucocorticoid receptor gene or nuclear receptor sub-family 3, group C, member 1 (NR3C1) may predispose to type 2 diabetes mellitus, metabolic syndrome and depression. NR3C1 gene showed significantly decreased methylation levels in cord blood and placenta from GDM women compared with controls. Our aim was to study the level of expression of NR3C1 gene in human umbilical vein endothelial cells (HUVECs) of newborns from women with GDM depending on glycemic targets.

Materials and methods: The study included 52 women with GDM and 25 women without GDM (control group). GDM patients were randomized to 2 groups per target glycemic levels: GDM1 (more tight glycemic targets, fasting blood glucose <5.1 mmol/l and <7.0 mmol/l postprandial, n=28) and GDM2 (less tight glycemic targets, <5.3 mmol/l and <7.8 mmol/l, respectively, n=24). The diagnosis of GDM was based on IADPSG criteria. HUVECs were isolated, expanded in vitro up to passage 2 and tested for viability and replicative senescence. The level of genes expression was determined by RT-PCR. Women with GDM kept electronic nutrition and glycemic control diaries with the help of a specially developed mobile application and sent data to the doctor. According to the personal diaries automatic calculations of integral indicators characterizing self-control of glycaemia (mean fasting and postprandial glycaemia) and food intake (amount of carbohydrates, proteins, fat and kalories) were accomplished. Statistical analysis included Kruskal-Wallace test, Mann-Whitney test and Spearman correlations.

Results: The level of NR3C1 gene expression was significantly lower in GDM1 and GDM2 group compared to controls (2.3±0.8, 2.4±1.2, and 3.1±1.2, respectively, P=0.005), with no difference between GDM1 and GDM2. Age and pregestational BMI did not differ among the three groups. Some negative correlations have been observed between the level of NR3C1 gene expression and the following parameters: fasting plasma glucose (PG) level (r=-0.331, P=0.004) and 2 h PG in OGTT (r=−0.253, P=0.033), fasting blood glucose (BG) (r=−0.397, P=0.003), and postprandial BG (r=−0.276, P=0.046) measured by participants during the study.

Conclusion: NR3C1 gene expression was down regulated in HUVECs of newborns from GDM mothers and was associated with fasting and postprandial levels of BG during GDM treatment. However, it was not associated with prespecified glycemic targets.