8-hydroxy-2--deoxyguanosine and Diabetes--Gestational

The growing clinical and epidemiological significance of gestational diabetes mellitus results from its constantly increasing worldwide prevalence, obesity, and overall unhealthy lifestyle among women of childbearing age. Oxidative stress seems to be the most important predictor of gestational diabetes mellitus development. Disturbances in the cell caused by oxidative stress lead to different changes in biomolecules, including DNA. The nucleobase which is most susceptible to oxidative stress is guanine. Its damage results in two main modifications: 8-hydroxy-2'-deoxyguanosineor 8-oxo-7,8-dihydro-2'-deoxyguanosine. Their significant level can indicate pathological processes during pregnancy, like gestational diabetes mellitus and probably, type 2 diabetes mellitus after pregnancy. This review provides an overview of current knowledge on the use of 8-hydroxy-2'-deoxyguanosineand/or 8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker in gestational diabetes mellitus and allows us to understand the mechanism of 8-hydroxy-2'-deoxyguanosineand/or 8-oxo-7,8-dihydro-2'-deoxyguanosine generation during this disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Pregnancy; Pregnancy in Diabetics

Pregnancy complications including pre-eclampsia, gestational-diabetes mellitus, preterm birth and intrauterine growth restriction can cause acute and chronic health problems for the mother and lead to fetal loss or dysregulation of infant physiology. The human placenta is susceptible to oxidative stress and oxidative damage in early gestation contributes to the onset of these conditions later in pregnancy. Current methods of predicting pregnancy complications are limited and although a large number of factors are associated with disease progression, few biomarkers have been used to aid in disease diagnosis early in gestation. This review discusses the detection of oxidative stress markers in biological fluids and highlights the need for further studies to validate their use in the prediction or diagnosis of pregnancy disorders.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Deoxyguanosine; Diabetes, Gestational; Female; Fetal Growth Retardation; Glycation End Products, Advanced; Humans; Lipoproteins, LDL; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Protein Carbonylation; Tyrosine

This study aims to assess the relationship between oxidative DNA damage and iron status in women with gestational diabetes mellitus (GDM) compared to those with normal glucose tolerance in the first and the second trimesters of pregnancy. Maternal serum and urine samples were collected in the 11th-14th weeks and the 24th-28th weeks of gestation. In addition to oral glucose tolerance test in the second trimester, fasting blood glucose, HbA1c, ferritin and hemoglobin levels were measured in blood samples. Urinary levels of oxidative DNA damage products 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and 8,5'-cyclo-2'-deoxyadenosines (S-cdA, R-cdA) were determined using liquid chromatography-tandem mass spectrometry with isotope-dilution. In the first trimester, urinary 8-OH-dG levels were found higher in the GDM group (n = 33) than in the control group (n = 84) (p = 0.006). R-cdA and S-cdA levels were not significantly different between the two groups (p = 0.794 and p = 0.792 respectively). When the cases were stratified according to their first trimester ferritin levels, women with ≥50th centile (≥130 ng/mL) demonstrated higher levels of 8-OH-dG and R-cdA than those under <50th centile (p = 0.034, p = 0.009). In the GDM group, there was a positive correlation between the second trimester 8-OH-dG and ferritin and 1st-hour glucose levels (p = 0.014, p = 0.020). This is the first study where oxidative DNA damage is evaluated in both early and late periods of pregnancy. Our findings reveal an association between GDM and iron status and oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Blood Glucose; Chromatography, Liquid; Deoxyadenosines; Diabetes, Gestational; DNA Damage; Female; Humans; Iron; Oxidative Stress; Pregnancy; Pregnancy Trimester, First

Objective To compare the level of oxidative deoxyribonucleic acid (DNA) damage (genotoxicity) between the offspring of mothers with and without diabetes diagnosed during pregnancy and its association with maternal body mass index (BMI). Methods We measured 8-hydroxy-deoxyguanosine (8-OH-dG), a marker of DNA oxidative damage, in venous umbilical cord plasma from newborns of mothers with (n=34) and without (n=56) diabetes diagnoses obtained during pregnancy. Two markers of oxidative stress - namely, nitric oxide degradation products (NOx) and total glutathione (GSH) - were quantified in both mothers and newborns. The effects of BMI, glycated hemoglobin (HbA1c), age and delivery mode were also analyzed. Results Newborns of mothers with diabetes during pregnancy exhibited higher levels of 8-OH-dG than those of mothers without diabetes (P<0.001). The other markers of oxidative stress were also higher in both mothers with diabetes and their newborns, with the exception of NOx in the mothers. The association of diabetes with 8-OH-dG was independent of other analyzed factors. Conclusion The offspring of mothers with diabetes during pregnancy are born with increased genotoxicity than the offspring of mothers without diabetes. BMI and HbA1c display an independent association with 8-OH-dG, particularly in the offspring of mothers not diagnosed with diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Deoxyguanosine; Diabetes, Gestational; DNA Damage; Female; Humans; Infant, Newborn; Obesity; Oxidative Stress; Pregnancy; Young Adult

We investigated whether gestational diabetes mellitus (GDM) and gestational arterial hypertension (GH) are associated with increased oxidative stress and DNA damage. Study included 3 groups of pregnant women (GDM, GH and control). DNA damage biomarkers (micronuclei MNi, nucleoplasmic bridges NPBs and nuclear buds NBUDs) were assessed by cytokinesis-block micronucleus cytome assay. Oxidative stress levels were evaluated by analyzing malondialdehyde equivalents (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Genotoxic effect of methyldopa, drug used to treat GH, was evaluated in in vitro experiment. TBARS levels, MNi, NPBs and NBUDs frequencies were significantly increased in both GDM and GH group. Concentrations of 8-OHdG were significantly higher in GDM than in other groups. Since methyldopa did not affect MNi, NPBs and NBUDs frequencies, nor TBARS and 8-OHdG levels, we concluded that methyldopa has no genotoxic effect. Thus, even when hyperglycemia or hypertension are present only during pregnancy they induce oxidative stress, DNA damage and chromosomal aberrations.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Cytokinesis; Deoxyguanosine; Diabetes, Gestational; DNA Damage; Female; Humans; Hypertension, Pregnancy-Induced; Lymphocytes; Methyldopa; Micronuclei, Chromosome-Defective; Micronucleus Tests; Oxidative Stress; Pregnancy; Thiobarbituric Acid Reactive Substances; Young Adult

In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF).. We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced ty the concentration of specific biomarkers in AF.. 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively.. The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231-268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001).. We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Birth Weight; Chromatography, High Pressure Liquid; Chronic Disease; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes, Gestational; Erythropoietin; Female; Fetal Hypoxia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoassay; Infant, Newborn; Insulin; Male; Nitrosation; Oxidative Stress; Pilot Projects; Pregnancy; Pregnancy in Diabetics; Tandem Mass Spectrometry; Tyrosine; Young Adult

To examine the association of maternal early pregnancy oxidative stress with risk of gestational diabetes mellitus (GDM).. A pilot prospective, nested case-control study was conducted. Study participants were recruited before 20weeks gestation. Maternal urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of systemic oxidative DNA damage and repair, was measured using competitive immunoassays. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95%CI).. Elevations in early pregnancy urinary 8-OHdG concentrations were associated with increased GDM risk. After adjusting for confounders, the OR for extreme quartiles (≥8.01 vs. <4.23ng/mg creatinine) of 8-OHdG was 3.79 (95%CI 1.03-14.00). The risk for GDM was highest for overweight women with urine 8-OHdG concentrations ≥8.01ng/mg creatinine (OR=5.36, 95%CI 1.33-21.55) when compared with lean women who had 8-OHdG concentrations <8.01ng/mg creatinine.. Elevated urine 8-OHdG concentrations in early pregnancy appear to be associated with increased GDM risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Case-Control Studies; Confidence Intervals; Demography; Deoxyguanosine; Diabetes, Gestational; DNA Damage; Female; Humans; Odds Ratio; Oxidative Stress; Pilot Projects; Pregnancy; Risk Factors; Washington; Young Adult