Abstract

The molecular aetiology of disturbed embryogenesis and other unfavourable outcomes in offspring of diabetic mothers is not fully understood. Experimental studies have suggested an involvement of radical oxygen species (ROS) in the teratological process. To investigate if maternal diabetes in humans is capable of inducing alterations in vascular oxidative stress parameters and whether such changes are associated with disturbances in foetal development. Seventy patients with pre-gestational diabetes (PGDM) were chosen for the study: 29 (41.4%) belonged to class B according to White, 15 (21.4%) to class C, 8 (11.4%) to class D, 3 (4.3%) to class F, 3 to class R and 12 (17.1%) to class F/R. In 20 (28.6%) patients from this group an unfavourable outcome was noted. All patients were subjected to intensive insulin therapy. Glycaemia was estimated by daily self-monitoring, and diurnal glucose profiles and glycated haemoglobin (HbA1c) concentrations were measured monthly. Oxidative stress was evaluated as changed superoxide dismutase, catalase and glutathione peroxidase activities as well as of malondialdehyde (MDA) and peroxides concentrations in maternal erythrocytes and blood serum. Prior to conception, the mean glycaemia in the group that had a planned pregnancy was 6.6mmol/l and HBA1c was 9.35%. Throughout the course of pregnancy, these parameters were maintained at a level of 6.7 mmol/l and 7.85%, respectively. The activity of all antioxidative enzymes was lower before than during pregnancy, and so was the concentration of MDA. The MDA concentrations were higher in patients with elevated glycaemia and with an unfavourable outcome. The investigated ROS, the glycaemia level, as well as the concentration of HBA1c did not show any significant differences between pregnancies with and without vascular complications. Patients with a favourable perinatal outcome presented a higher activity of antioxidant enzymes, than those with unfavourable outcome, throughout the whole course of pregnancy. The appearance of unfavourable perinatal outcomes in relation to parameters of oxidative stress was assessed by logistic regression. Both SOD and GPX activities, as well as peroxides' concentration, showed significant correlations (p < 0.005) with foetal complications. However, after mean glucose levels in the studied group were included into these analyses, this relationship was only evident with SOD and GPX activity (p < 0.0016). Oxidative stress is one of several important factors contributing to unfavourable outcome of human diabetic pregnancy.

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