Investigation of the relationship between iron levels and oxidative DNA damage in pregnant women with gestational diabetes mellitus and impaired glucose tolerance

Gestational diabetes mellitus (GDM) is a clinical disorder characterized by high glucose levels occurring for the first time during pregnancy; the most common metabolic complication of pregnancy. On the other hand, iron deficiency anemia is common in pregnant women. Although iron is an essential trace element for growth and development, iron supplementation in non-anemic pregnant women induces iatrogenic iron excess. Iron excess is thought to cause oxidative stress and GDM. In this study, we evaluated oxidative DNA damage as a sensitive indicator of cumulative oxidative stress in urine and blood samples taken at 11-14 weeks and 24-28 weeks of gestation in pregnant women with GDM and normal glucose tolerance. We also aimed to examine the relationship between the levels of DNA damage products and iron status. Our study was designed as a prospective study between March 2016 and August 2018. The study groups were composed of 117 volunteers, GDM (33) and control group (84) with normal glucose tolerance. The first urine samples at morning were taken in 11-14. weeks from the pregnant women who participated in the study and at the 24-28. weeks when they had visited for routine 75 g. glucose screening and diagnostic test (OGTT). Demographic data and oral iron supplements status of the pregnant women were recorded who applied to the Department of Obstetrics and Gynecology, Pregnant Polyclinic. Urinary creatinine and fasting blood glucose (FBG), HbA1c, ferritin, hemogram values were measured in venous blood samples taken for routine control. The diagnosis of GDM was made according to ADA 2017 criteria using OGTT results for 24-28 weeks. In the third month, 8-OH-dG levels of GDM group were significantly higher than the control group (p = 0.006). Although the 8-OH-dG levels in the sixth month of the GDM group were higher than the control group, no statistical significance was observed. At the third month, fasting blood glucose levels of the GDM group and at the 6th month, OGTT values at the 0., 1st, and 2nd hours were significantly higher than the control group values (p <. 001). Although the ferritin levels of the GDM group were found to be higher than the control group, there was no statistical significance. In our study, when the longitudinal changes in the parameters between the end of the first and second trimester were examined, although insignificant, the 8-OH-dG levels were decreased from 3-month-to-6-month in pregnants of both groups. In the control group ferritin, hemoglobin and HbA1c values were lower in the sixth month compared to the third month (p <0.001). There was no difference between the two pregnancy terms regarding other parameters investigated. When all of the pregnant women who participated in our study were ranked from low to high according to ferritin levels at the 3rd month, 8-OH-dG and R-cdA values of pregnant women over 50 percentile (Ferritin ≥ 13.0 ng / mL) were found to be significantly higher than the ones below 50 percentile (p = 0.034, p = 0.009). When only the control group pregnants were ranked according to ferritin levels from low to high in the third month, similarly, 8-OH-dG values were higher than the ones below 50 percentile (Ferritin ≥ 11.9 ng / mL) (p = 0.017). As the relationship between the parameters examined in our study; in both the GDM group and the control group, the 6th month R-cdA had a positive correlation with S-cdA at the 6th month (r = 0.549, p = 0.003 and r = 0.504, p <0.001, respectively). There was a significant positive correlation between the 3rd month R-cdA and 3rd month S-cdA and 8-OH-dG levels in the control group (r = 0.456, p <0.001 and r = 0.364, p = 0.001, respectively). In the control group, a positive correlation was found between the 3rd month ferritin levels and 3rd month S-cdA and 8-OH-dG levels (r = 0.279, p = 0.011 and r = 0.256, p = 0.019, respectively). In the GDM group, there was a positive correlation between 8-OH-dG levels at 6th month and ferritin and OGTT 1st hour glucose values at 6th month (r = 0.466, p = 0.014 and r = 0.452, p = 0.020, respectively). Our study is the first one to investigate oxidative DNA damage in the late and early stages of pregnancy and to correlate pregnant women with the status of body iron. The results of our study showed that pregnant women who were diagnosed with gestational diabetes with OGTT at the end of second trimester were more exposed to oxidative DNA damage in early pregnancy, compared to pregnant women with normal glucose tolerance; For the first time it was shown that, in the early period, in the pregnants with higher 8-OH-dG levels, measured with the reference tandem mass spectrometric method, the ratio of future GDM diagnosis was higher compared the lower ones according to the cut-off level. These results suggest that non-invasive urine DNA damage measurements to be performed in the early period in pregnant women may be useful in predicting the future GDM. According to the results of our study, it was found that oxidative DNA damage parameters were significantly lower in the group with lower levels of depot iron and a strong relationship between iron level and oxidative stress in pregnant women. We anticipate that, future studies with more pregnant women with gestational diabetes will help to clarify the relationship between oxidative stress and GDM-iron.