Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes

doi:10.1016/j.clinbiochem.2003.12.005

Clinical Biochemistry

Volume 37, Issue 4, April 2004, Pages 293-298

https://doi.org/10.1016/j.clinbiochem.2003.12.005 Get rights and content

Abstract

Objectives: To evaluate oxidative and antioxidative status in pregnant diabetic women between 26 and 32 weeks of gestation.

Design and Methods: Free and total malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and vitamins A and E were determined in plasma and erythrocytes of 54 pregnant women. Among these, 27 were diabetics with either gestational diabetes mellitus (GDM), sub-group I, or previous insulin-dependent diabetes mellitus (type 1 diabetes), sub-group II. The other 27 patients were controls. Fasting plasma glucose and HbA_1c levels were determined in all women.

Results: HbA_1c levels, plasma-, and erythrocyte-free MDA levels were significantly higher in all diabetic women and in both sub-groups than in controls. Plasma vitamin E and erythrocyte vitamin A levels were significantly lower in all diabetic women than in controls. Moreover, GPX and SOD activities were significantly reduced in all diabetic women, GPX in both sub-groups and SOD only in type 1 diabetes.

Conclusions: The increased oxidative stress we demonstrated in pregnant women with previous type 1 diabetes or with GDM should be monitored by strictly controlling blood glucose during pregnancy with stringent recommendations and perhaps antioxidant supplementation.

Introduction

Diabetes during gestation is associated with an increased risk of fetal and maternal complications [1]. However, the mechanisms by which diabetes leads to greater fetal abnormalities and maternal vascular complications such as preeclampsia have not been well established. The clinical manifestations of diabetes in pregnancy have been attributed to fetal hyperglycemia, hyperlipidemia, hyperinsulinemia, or placental endothelial dysfunction [2]. The involvement of oxidative stress was recently suggested [3], [4], [5].

Oxidative stress may be increased in diabetes owing to a hyperproduction of reactive oxygen species (ROS) such as O₂⁻, OH, and H₂O₂, or a deficiency in the antioxidant defense system. The increased production of ROS has been attributed to protein glycation [6], [7] and glucose auto-oxidation in a hyperglycemic environment [8]. Impaired radical scavenger function has been linked to the decreased activity of enzymatic and non-enzymatic scavengers. In particular, the action of superoxide dismutase (SOD), which catalyzes the dismutation of O₂⁻ into H₂O_2, has been found to be decreased in the erythrocytes of diabetic rats [9] and diabetic humans [10]. Similarly, a reduction in the action of glutathione peroxidase (GPX) and catalase (CAT), enzymes involved in the detoxification of H₂O₂, has been observed in chronic diabetes [11]. Among the non-enzymatic scavengers, vitamin E, the main intra-cellular antioxidant, has been found to be decreased in diabetic patients [12]. Moreover, experimental studies have found evidence for free oxygen radical activity in the embryos of diabetic rats. This activity is thought to be the cause of the teratogenicity of diabetic pregnancy [13], [14], [15]. Furthermore, it has been demonstrated that antioxidative therapy blocks diabetes-induced embryonic dysmorphogenesis in vivo and in vitro [16], although the mechanism for this protection remains to be elucidated. On the other hand, it is known that good perinatal outcomes can be achieved in diabetic pregnancies only by normalizing glucose values [17], [18], [19].

The aim of the study was to evaluate oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes and to compare them to those of control pregnant women without diabetes, matched for age, BMI, and gestational age at the same period of gestation.

Section snippets

Patients

Overall, 54 women with singleton pregnancy between 26 and 32 weeks of gestation were registered as new patients in the Department of Obstetrics and Gynecology in Bordeaux University Hospital between January and December 2000. In 27 women, pregnancy was complicated by diabetes diagnosed either during gestation (gestational diabetes mellitus, GDM) or before (insulin-dependent diabetes mellitus, type 1 diabetes). The other 27 pregnant women had a negative 100-g oral glucose tolerance test (OGTT)

Results

The main characteristics of the population are presented in Table 1. Fasting plasma glucose levels were similar in diabetic pregnant women, whatever the type of diabetes, and in corresponding controls. Glycemic metabolic control is reflected by HbA_1c percentage. While the mean of HbA_1c of the controls was in the normal range of 4.92 ± 0.08%, women with GDM at diagnosis and enrolment before dietary advice had a higher HbA_1c mean (5.54 ± 0.07%) than their respective controls (P < 0.001). Women

Discussion

This study comparing oxidative stress and antioxidant status in pregnant women with diabetes and in healthy pregnant women at the same period of gestation (26–32 weeks) showed a significantly higher content of lipoperoxidation breakdown products and a decrease in antioxidant defense systems both in the plasma and RBC of all diabetic women. Moreover, concerning the sub-groups of diabetes, oxidative stress was present in type 1 diabetes and also in GDM but to a lesser degree.

For the women with

References (48)

L. Baker et al.
Diabetic embryopathy: a selective review of recent trends
J. Diabets Complicat.
(1993)
D. Carone et al.
Lipid peroxidation products and antioxidant enzymes in red blood cells during normal and diabetic pregnancy
Eur. J. Obstet. Gynecol. Reprod. Biol.
(1993)
H. Nasrat et al.
Determinants of pregnancy outcome in patients with gestational diabetes
Int. J. Gynaecol. Obstet.
(1996)
M.W. Carpenter et al.
Criteria for screening tests for gestational diabetes
Am. J. Obstet. Gynecol.
(1982)
J.M.C. Gutteridge
The use of standard of malondialdehyde
Ann. Biochem.
(1975)
E. Peuchant et al.
Lipoperoxidation in plasma and red blood cells of patients undergoing haemodialysis: vitamins A, E and iron status
Free Radic. Biol. Med.
(1994)
P.M. Catalano et al.
Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus
Am. J. Obstet. Gynecol.
(1999)
E. Sivan et al.
Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and biochemical analysis
Am. J. Obstet. Gynecol.
(1996)
D.C. Kuhn et al.
Alterations in transfer and lipid distribution of arachidonic acid in placentas of diabetic pregnancies
Diabetes
(1990)
H. Forsberg et al.
Altered levels of scavenging enzymes in embryos subjected to a diabetic environment
Free Radic. Res.
(1996)

D.R. Coustan et al.

Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia, operative delivery, and birth trauma

Am. J. Obstet. Gynecol

(1984)

P. Gillery et al.

Glycation of proteins as a source of superoxide

Diabetes Metab.

(1988)

J.W. Baynes

Role of oxidative stress in development of complication in diabetes

Diabetes

(1991)

J.V. Hunt et al.

Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose

Diabetes

(1990)

D. Loven et al.

Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozotocin-induced diabetes

Diabetes

(1986)

E. Peuchant et al.

Short-term insulin therapy and normoglycemia: effects on erythrocyte lipid peroxidation in NIDDM patients

Diabetes Care

(1997)

S.A. Wohaieb et al.

Alterations in free radical tissue-defense mechanism in streptozotocin-induced diabetes in rats. Effects of insulin treatment

Diabetes

(1987)

M.G. Vandewoude et al.

Vitamin E status in normocholesterolemic and hypercholesterolemic diabetic patients

Acta Diabetol. Lat.

(1987)

R.A. Trocino et al.

Significance of glutathione depletion and oxidative stress in early embryogenesis in glucose-induced rat embryo culture

Diabetes

(1995)

X. Yang et al.

Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose

Am. J. Physiol.

(1997)

U.J. Eriksson et al.

Diabetes and embryonic malformations. Role of substrate-induced free-oxygen radical production for dysmorphogenesis in cultured rat embryos

Diabetes

(1993)

U.J. Eriksson et al.

Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring

Diabetes

(1996)

B. Rosenn et al.

Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus

Obstet. Gynecol.

(1994)

M.F. Greene et al.

First-trimester hemoglobin A₁ and risk for major malformation and spontaneous abortion in diabetic pregnancy

Teratology

(1989)

Cited by (136)

Altered sperm fate in the reproductive tract milieu due to oxidative stress leads to sub-fertility in type 1 diabetes females: A Drosophila-based study
2023, Life Sciences
Citation Excerpt :
The increased MDA and PC content point to the insufficiency of this antioxidant machinery in mitigating the oxidative stress in Df[dilp1–5] females. These findings are congruent with the increased oxidative stress in T1D females [19,20,63,64]. Increased levels of ROS, lipid peroxidation and protein carbonylation in Df[dilp1–5] females in the present study also match the earlier reports in T1D patients [18,20,65–67] and T1D rat models [68].
Female sub-fertility, a prominent complication due to Type 1 diabetes (T1D), is generally attributed to disturbances in menstrual cycles and/or ovarian defects/disorders. T1D women, however, are high in oxidative stress, although the impact of the same on their reproduction and associated events remains unknown. Therefore, we assessed the repercussions of elevated oxidative stress on the sperm fate (storage/utilization) in the reproductive tract milieu of T1D females and their fertility using the Drosophila T1D model (Df[dilp1–5]), which lacks insulin-like peptides and displays reduced female fertility.
We mated Df[dilp1–5] females to normal males and thereafter examined sperm storage and/or utilization in conjunction with oxidative stress parameters in mated Df[dilp1–5] females at different time points. Also, the impact of antioxidant (Amla or Vitamin C) supplementation on the above oxidative stress parameters in Df[dilp1–5] females and the consequences on their sperm and fertility levels were examined.
Df[dilp1–5] females showed elevated oxidative stress parameters and a few of their reproductive tract proteins are oxidatively modified. Also, these females stored significantly fewer sperm and also did not utilize sperm as efficiently as their controls. Surprisingly, amelioration of the oxidative stress in Df[dilp1–5] females' milieu through antioxidant (Amla or vitamin C) supplementation enhanced sperm storage and improved fertility.
Hyperglycemia coupled with elevated oxidative stress within the female reproductive tract environment affects the sperm fate, thereby reducing female fertility in T1D. In addition, these findings suggest that antioxidant supplementation may substantially aid in the mitigation of sub-fertility in T1D females.
Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases
2022, Journal of Ethnopharmacology
Tinospora cordifolia (Willd.) Miers (Menispermaceae) is a Mediterranean herb, used in Ayurvedic, Siddha, Unani, and folk medicines. The herb is also used in conventional medicine to treat oxidative stress-related diseases and conditions, including inflammation, pain, diarrhea, asthma, respiratory infections, cancer, diabetes, and gastrointestinal disorders.
The taxonomy, botanical classification, geographical distribution, and ethnobotanical uses of T. cordifolia, as well as the phytochemical compounds found in the herb, the toxicology of and pharmacological and clinical studies on the effects of T. cordifolia are all covered in this study.
To gather information on T. cordifolia, we used a variety of scientific databases, including Scopus, Google Scholar, PubMed, and Science Direct. The information discussed focuses on biologically active compounds found in T. cordifolia, and common applications and pharmacological activity of the herb, as well as toxicological and clinical studies on its properties.
The findings of this study reveal a connection between the use of T. cordifolia in conventional medicine and its antioxidant, anti-inflammatory, antihypertensive, antidiabetic, anticancer, immunomodulatory, and other biological effects. The entire plant, stem, leaves, root, and extracts of T. cordifolia have been shown to have a variety of biological activities, including antioxidant, antimicrobial, antiviral, antiparasitic, antidiabetic, anticancer, anti-inflammatory, analgesic and antipyretic, hepatoprotective, and cardioprotective impact. Toxicological testing demonstrated that this plant may have medicinal applications. T. cordifolia contains a variety of biologically active compounds from various chemical classes, including alkaloids, terpenoids, sitosterols, flavonoids, and phenolic acids. Based on the reports researched for this review, we believe that chemicals in T. cordifolia may activate Nrf2, which leads to the overexpression of antioxidant enzymes such as CAT, GPx, GST, and GR, and thereby induces the adaptive response to oxidative stress. T. cordifolia is also able to reduce NF-κB signalling by inhibiting PI3K/Akt, activating AMPK and sirtuins, and downregulating PI3K/Akt.
Our findings indicate that the pharmacological properties displayed by T. cordifolia back up its conventional uses. Antimicrobial, antiviral, antioxidant, anticancer, anti-inflammatory, antimutagenic, antidiabetic, nephroprotective, gastroprotective, hepatoprotective, and cardioprotective activities were all demonstrated in T. cordifolia stem extracts. To validate pharmacodynamic targets, further research is needed to evaluate the molecular mechanisms of the known compounds against gastrointestinal diseases, inflammatory processes, and microbial infections, as immunostimulants, and in chemotherapy. The T. cordifolia safety profile was confirmed in a toxicological analysis, which prompted pharmacokinetic assessment testing to confirm its bioavailability.
Association between early oxidative DNA damage and iron status in women with gestational diabetes mellitus
2021, Reproductive Toxicology
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.
Telomere erosion as a placental clock: From placental pathologies to adverse pregnancy outcomes
2020, Placenta
The placenta provides nutritional and gas exchange between fetus and mother. Early in pregnancy, placental trophoblasts proliferate rapidly and invade aggressively. As pregnancy progresses, placental cells begin to age. Indeed, pregnancy itself has a tightly regulated duration, determined in large part by placental lifespan. Late in pregnancy, placental cells reach a senescent apoptotic state, activated by a number of intrinsic and extrinsic factors, including oxidative stress (OS), and DNA damage. Pregnancy complications, stillbirths and neonatal deaths have been related to OS and abnormal placental aging. Telomeres, the protective nucleoprotein structures at the ends of linear chromosomes, shorten both from cell replication and from exposure to OS. When telomeres become critically short they trigger cell cycle arrest and eventually cell death. Telomere attrition thus provide an intrinsic mechanism to explain tissue senescence and aging. Mounting evidence suggests that senescence of placental and fetal membrane cells results from telomere attrition. We review the studies that have addressed the role of telomere length (TL) in placentas from normal and complicated pregnancies, including pre-eclampsia, intrauterine growth restriction, gestational diabetes, and stillbirth. To date studies have uncovered associations between TL and a number of obstetrical complications. Future research is needed to determine whether these associations are causative, i.e. whether these clinical conditions result from telomere dysfunction, and whether particular features of telomeres, e.g. mean or shortest length, etc. could serve as clinically useful biomarkers of placental health.
Lipid peroxidation mediated the association of urinary 1-bromopropane metabolites with plasma glucose and the risk of diabetes: A cross-sectional study of urban adults in China
2020, Journal of Hazardous Materials
Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose–response relationship between BPMA and FPG levels with a β of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels.
Impaired Expression of Humanin during Adrenocortical Carcinoma
2024, International Journal of Molecular Sciences

View all citing articles on Scopus

View full text

Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes

Abstract

Introduction

Section snippets

Patients

Results

Discussion

J. Diabets Complicat.

Eur. J. Obstet. Gynecol. Reprod. Biol.

Int. J. Gynaecol. Obstet.

Am. J. Obstet. Gynecol.

Ann. Biochem.

Free Radic. Biol. Med.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Alterations in transfer and lipid distribution of arachidonic acid in placentas of diabetic pregnancies

Diabetes

Altered levels of scavenging enzymes in embryos subjected to a diabetic environment

Free Radic. Res.

Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia, operative delivery, and birth trauma

Am. J. Obstet. Gynecol

Glycation of proteins as a source of superoxide

Diabetes Metab.

Role of oxidative stress in development of complication in diabetes

Diabetes

Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose

Diabetes

Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozotocin-induced diabetes

Diabetes

Short-term insulin therapy and normoglycemia: effects on erythrocyte lipid peroxidation in NIDDM patients

Diabetes Care

Alterations in free radical tissue-defense mechanism in streptozotocin-induced diabetes in rats. Effects of insulin treatment

Diabetes

Vitamin E status in normocholesterolemic and hypercholesterolemic diabetic patients

Acta Diabetol. Lat.

Significance of glutathione depletion and oxidative stress in early embryogenesis in glucose-induced rat embryo culture

Diabetes

Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose

Am. J. Physiol.

Diabetes and embryonic malformations. Role of substrate-induced free-oxygen radical production for dysmorphogenesis in cultured rat embryos

Diabetes

Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring

Diabetes

Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus

Obstet. Gynecol.

First-trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy

Teratology

First-trimester hemoglobin A₁ and risk for major malformation and spontaneous abortion in diabetic pregnancy