ECE2019 Guided Posters Gestational and Type 1 Diabetes (11 abstracts)
1Almazov National Medical Research Centre, Saint-Petersburg, Russian Federation; 2St Petersburg Pavlov State Medical University, Saint Petersburg, Russian Federation; 3Almazov National Medical Research Centre, Saint Petersburg, Russian Federation; 4Saint Petersburg State Electrotechnical University, Saint Petersburg, Russian Federation.
Background: Understanding the mechanism whereby the intrauterine hyperglycemia in women with gestational diabetes mellitus (GDM) affects the offspring predisposition to metabolic and cardiovascular diseases may help prevent their intergenerational transmission. Our aim was to study the effect of the degree and duration of maternal hyperglycemia on the level of expression of genes associated with cardio-metabolic diseases in human umbilical vein endothelial cells (HUVECs) of newborns from women with GDM.
Materials and methods: HUVECs were isolated from 75 women with GDM and 28 women without GDM (control group). Women with GDM treated for GDM starting before 30-th week of gestation, were randomized to 2 groups per target glycaemic levels: GDM1 (tight glycaemic targets, fasting blood glucose <5.1 mmol/L and <7.0 mmol/L postprandial, N=34) and GDM2 (less tight glycaemic targets, <5.3 mmol/L and <7.8 mmol/L, respectively, N=29). Women with GDM who started treatment after 34-th week of gestation (N=11) were considered as late treatment group (GDM3). The level of ICAM1, VCAM1, ANGPTL4, ENG, TRIB1, MT-ND2, TFAM, PTGS1, MEST, PLAC8 and NR3C1 genes expression in HUVECs was determined by RT-PCR.
Results: The four groups did not differ by maternal age and pregestational body mass index. GDM groups (GDM1, GDM2 and GDM3) showed significantly reduced levels of ANGPTL4 gene expression compared to the control group (24.7±26.1, 26.1±40.1, 13.4±11.9 vs 91.6±100.5, respectively, P=0.009, 0.014 and 0.002), but no difference was observed among GDM groups. NR3C1 gene expression also tended to be lower in all GDM groups compared to controls (4.6±2.5, 4.6±1.7, 3.4±1.8 vs 6.0±1.3, respectively, P=0.093, 0.051 and 0.006) with no difference among GDM groups. TRIB1 gene expression was lower in GDM3 compared to GDM1, GDM2 and control group (9.0±4.9 vs 23.8±23.9, 28.5±27.2, 21.9±4.1, respectively, P=0.008, P=0.004 and P=0.001) with no difference among GDM1, GDM2 and control group. GDM1 group achieved lower levels of 1 hour postprandial glucose compared to GDM2 during the whole period of the study (6.0±0.4 vs 6.3±0.5 mmol/L, P=0.036).
Conclusion: The decrease in ANGPTL4 and NR3C1 genes expression level has been detected in HUVECs of newborns from women with GDM compared to control group. However their expression was not associated with the intensity of glycaemic control and the duration of maternal hyperglycemia. The duration of maternal hyperglycemia was associated with TRIB1 gene expression which was decreased only in the late treatment group.