ascorbic-acid and Diabetes--Gestational

Growing evidence suggests that vitamin C supplementation may be an effective adjunct therapy in the management of people with diabetes. This paper critically reviews the current evidence on effects of vitamin C supplementation and its potential mechanisms in diabetes management. Evidence from meta-analyses of randomized controlled trials (RCTs) show favourable effects of vitamin C on glycaemic control and blood pressure that may be clinically meaningful, and mixed effects on blood lipids and endothelial function. However, evidence is mostly of low evidence certainty. Emerging evidence is promising for effects of vitamin C supplementation on some diabetes complications, particularly diabetic foot ulcers. However, there is a notable lack of robust and well-designed studies exploring effects of vitamin C as a single compound supplement on diabetes prevention and patient-important outcomes (i.e. prevention and amelioration of diabetes complications). RCTs are also required to investigate potential preventative or ameliorative effects of vitamin C on gestational diabetes outcomes. Oral vitamin C doses of 500-1000 mg per day are potentially effective, safe, and affordable for many individuals with diabetes. However, personalisation of supplementation regimens that consider factors such as vitamin C status, disease status, current glycaemic control, vitamin C intake, redox status, and genotype is important to optimize vitamin C's therapeutic effects safely. Finally, given a high prevalence of vitamin C deficiency in patients with complications, it is recommended that plasma vitamin C concentration be measured and monitored in the clinic setting.

Topics: Ascorbic Acid; Diabetes, Gestational; Diabetic Foot; Dietary Supplements; Female; Humans; Pregnancy; Vitamins

Gestational Diabetes Mellitus (GDM) is a significant health concern in pregnant women and their offspring. Although Vitamin C is known to play a role in maintaining normal physiological processes, its relationship with GDM has not been fully elucidated.. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, analyzing data from 15 studies selected from PubMed, Embase, Web of Science, and the Cochrane Library up to May 16, 2023. These studies were selected based on inclusion criteria such as study design, outcome of interest, exposure factor, and data extractability. Quality assessment was performed using the Newcastle-Ottawa Scale. We assessed the heterogeneity between studies and conducted a sensitivity analysis.. Data from 10,131 subjects, including 1304 diagnosed GDM cases, were analyzed. The meta-analysis showed that women in the low Vitamin C exposure group had higher odds of developing GDM (odds ratio 2.72, 95% CI:1.24-4.19). There was a greater likelihood of increased GDM risk with lower Vitamin C exposure (standardized mean difference: -0.71, 95% CI [-1.07 -0.36]). Subgroup analysis revealed that both internal and external Vitamin C exposure, along with exposure during the second or third trimester of pregnancy, was associated with higher GDM incidence rates under low Vitamin C exposure. Sensitivity analysis confirmed the robustness of the results, and no significant publication bias was detected.. Low Vitamin C exposure during pregnancy may increase the risk of GDM. Given these findings, it could be beneficial for pregnant women to increase their intake of Vitamin C-rich foods and to ensure adequate blood Vitamin C levels as a preventive measure against GDM.

Topics: Ascorbic Acid; Diabetes, Gestational; Female; Humans; Nutritional Status; Pregnancy; Pregnancy Trimester, Third; Vitamins

To examine the effect of antioxidant administration on the oxidative parameters in both blood and placental tissue and its relation to fetal outcome in women with GDM.. Two-hundred pregnant women with gestational diabetes mellitus (GDM) were randomized into 2 groups, Group1 received 1 gram L-ascorbic acid per day and Group2 received placebo.. The use of antioxidants significantly lower the needed insulin dose for blood sugar control (25.6 ± 20.3 versus 40.5 ± 23.7, respectively). In placental tissue homogenates, glutathione (GSH) was 49.6 ± 5.9 versus 62.34 ± 4.99, malondialdahyde (MDA) was 165.7 ± 9.2 versus 264.15 ± 12, superoxide dismutase (SOD) was 0.3 ± 0.3 versus 0.054 ± 0.16 while catalase (CAT) was 14.06 ± 2.4 versus 15.52 ± 3.97 and glutathione peroxidase (GPx) was 14 ± 4.1 versus 26.3 ± 4.26 in antioxidant group compared to the control group (p < 0.001). In maternal blood, GSH was 1.5 ± 0.3 versus 0.74 ± 0.088, CAT was 380.7 ± 11 versus 325.44 ± 21.8, GPx was 52.3 ± 8.7 versus 75.82 ± 6.84 and SOD was 188 ± 15.3 versus 98.56 ± 11.05 in antioxidant group compared to control group (p < 0.001). In neonatal blood, the level of MDA and SOD showed a statistically significant difference between antioxidants and control groups (4 ± 0.7 versus 6.6 7 ±0.66 and1 8 8 ± 15.3 versus 98.5 ± 11.05, respectively) (p < 0.001). The neonatal blood sugar after 1 and 2 hours of delivery was more stable in antioxidant group (56.7 ± 10.9 versus 39.7 ± 11.1 and 58.5 ± 10.8 versus 41.7 ± 13.1, respectively) (p <0.05). The neonates NICU admission was lower in antioxidant group (5 versus 11) (p <0.05).. The use of antioxidants markedly reverses the oxidative stresses in women with GDM with marked improvement on neonatal outcome.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Glucose; Diabetes, Gestational; Female; Fetus; Humans; Infant, Newborn; Neonatal Screening; Oxidative Stress; Placenta; Pregnancy; Pregnancy Outcome; Superoxide Dismutase; Ultrasonography, Prenatal; Young Adult

Topics: Administration, Oral; Adult; Ascorbic Acid; Blood Glucose; Brachial Artery; Diabetes Mellitus; Diabetes, Gestational; Double-Blind Method; Endothelium, Vascular; Female; Humans; Obesity; Postpartum Period; Vasodilation

Findings on the role of diet in non-alcoholic fatty liver disease (NAFLD) pathogenesis are inconsistent. There are few studies on the dietary habits of pregnant women with NAFLD. Our primary aim was to compare the dietary intakes of pregnant women with and without NAFLD.. This case-control study recruited 60 women (26-34 weeks' gestation) with recently diagnosed gestational diabetes (GDM) before any treatment was implemented. At recruitment, all participants underwent B-mode hepatic ultrasound. We included 30 women with sonographic NAFLD (cases) and 30 women without NAFLD (controls) matched for age, skin color, and pre-pregnancy body mass index. We assessed participants' dietary intakes in the last six months using a validated food frequency questionnaire. Mann-Whitney´s test was used to compare differences in median macro and micronutrient intakes between cases and controls.. Total median daily energy (1965.1 × 1949.2 calories) and lipid (25.1% × 28.3%) intakes were similar in women with and without NAFLD and fell within recommended ranges. Participants with NAFLD reported significantly higher median daily intakes of carbohydrates (59.4% × 53.1% p = 0.003), and significantly lower protein (15.6% × 17.0% p = 0.005), fiber (10.7 × 13.3 g/day p = 0.010), and vitamin C (151.8 × 192.6 mg/day p = 0.008) intakes than those without NAFLD.. Pregnant women with NAFLD ingest more carbohydrates and less protein, fiber, and vitamin C than those without NAFLD. Our findings contribute to understanding the role of diet in the development of NAFLD in pregnant women.

Topics: Ascorbic Acid; Case-Control Studies; Diabetes, Gestational; Eating; Female; Humans; Non-alcoholic Fatty Liver Disease; Pregnancy; Pregnant Women; Vitamins

Oxidative stress has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Vitamin C as natural antioxidant may help to increase the body's antioxidant capacity. The study is aimed to determine whether vitamin C intake during pregnancy is associated with lower risk of GDM.. Women with singleton pregnancy and without any history of diabetes were drawn from the ongoing Tongji Maternal and Child Health Cohort (TMCHC). Oral glucose tolerance tests (OGTT) were conducted during weeks 24-28 of gestation to screen for GDM. A validated food frequency questionnaire (FFQ) was used to assess dietary intake during mid pregnancy. Use of multivitamins and specific supplements of vitamin C was assessed by questionnaires. Odds ratios (ORs) of GDM risk were calculated by logistic regression models, adjusted for potential confounders.. 344 (11.4%) of the 3009 women were diagnosed with GDM. Dietary vitamin C intake was inversely associated with the risk of GDM. Women with above adequate dietary vitamin C intake (more than 200 mg/day) experienced lower odds of GDM (OR 0.68, 95% CI: 0.49-0.95) than those with adequate intake (115-200 mg/day). There was no association between the total consumption of vitamin C and the risk of GDM (OR 1.04, 95% CI: 0.71-1.53).. This data suggests that higher dietary consumption of vitamin C during pregnancy is independently associated with lower odds of GDM. Above 200 mg/day of dietary vitamin C intake may help reduce the odds of GDM. However, no such association between total vitamin C intake and the risk of GDM was found. Hence, sufficient vegetables and fruits rich in vitamin C should be recommended to protect pregnant women from developing gestational diabetes.

Topics: Adult; Ascorbic Acid; China; Cohort Studies; Diabetes, Gestational; Diet; Female; Humans; Longitudinal Studies; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Risk Assessment; Vitamins

This study aimed to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) and oxidative stress biomarkers in pregnant women with gestational diabetes mellitus (GDM), in order to demonstrate the involvement of oxidative stress in this condition, which presents pathophysiology still undetermined.. δ-ALA-D activity, lipid peroxidation estimated as the levels of thiobarbituric acid reactive substances (TBARS), protein (P-SH) and non-protein thiol (NP-SH) content, catalase (CAT) activity and concentration of vitamin C (VIT C) in samples of pregnant women with GDM (n = 48) and in healthy pregnant women (n = 30), who constituted the control group.. The δ-ALA-D activity was significantly lower in pregnant women with GDM compared to controls, as well as levels of thiols, VIT C and CAT activity. Lipid peroxidation was higher in GDM group.. The results suggest that the main factor for the increase in oxidative stress and reduced δ-ALA-D activity in diabetic pregnant women is gestational hyperglycemic environment, which changed the redox balance and interfered on mechanism of the δ-ALA-D activity in relation to normoglycemic pregnant women.

Topics: Adult; Ascorbic Acid; Biomarkers; Case-Control Studies; Catalase; Diabetes, Gestational; Erythrocytes; Female; Humans; Oxidative Stress; Porphobilinogen Synthase; Pregnancy; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances

Preeclampsia and gestational diabetes mellitus (GDM) are the most common clinical conditions in pregnancy that could result in adverse in utero environments. Fetal exposure to poor environments may raise the long-term risk of postnatal disorders, while epigenetic modifications could be involved. Recent research has implicated involvement of 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine, via oxidation by ten-eleven translocation (TET) enzymes, in DNA methylation-related plasticity. Here, we show that the TET2 expression and 5hmC abundance are significantly altered in the umbilical veins of GDM and preeclampsia. Genome-wide profiling of 5hmC revealed its specific reduction on intragenic regions from both GDM and preeclampsia compared to healthy controls. Gene Ontology analysis using loci bearing unique GDM- and preeclampsia-specific loss-of-5hmC indicated its impact on several critical biological pathways. Interestingly, the substantial alteration of 5hmC on several transposons and repetitive elements led to their differential expression. The alteration of TET expression, 5hmC levels and 5hmC-mediated transposon activity was further confirmed using established hypoxia cell culture model, which could be rescued by vitamin C, a known activator of TET proteins. Together, these results suggest that adverse pregnancy environments could influence 5hmC-mediated epigenetic profile and contribute to abnormal development of fetal vascular systems that may lead to postnatal diseases.

Topics: 5-Methylcytosine; Adult; Ascorbic Acid; Diabetes, Gestational; Dioxygenases; DNA Methylation; DNA Transposable Elements; DNA-Binding Proteins; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Humans; Pre-Eclampsia; Pregnancy; Proto-Oncogene Proteins

The aim of this work was to determine whether placental endoplasmic reticulum (ER) stress may contribute to the pathophysiology of gestational diabetes mellitus (GDM) and to test the efficacy of chemical chaperones and antioxidant vitamins in ameliorating that stress in a trophoblast-like cell line in vitro.. Placental samples were obtained from women suffering from GDM and from normoglycaemic controls and were frozen immediately. Women with GDM had 2 h serum glucose levels > 9.0 mmol/l following a 75 g oral glucose tolerance test and were treated with diet and insulin when necessary. Western blotting was used to assess markers of ER stress. To test the effects of hyperglycaemia on the generation of ER stress, a new trophoblast-like cell line, BeWo-NG, was generated by culturing in a physiological glucose concentration of 5.5 mmol/l (over 20 passages) before challenging with 10 or 20 mmol/l glucose.. All GDM patients were well-controlled (HbA1c 5.86 ± 0.55% or 40.64 ± 5.85 mmol/mol, n = 11). Low-grade ER stress was observed in the placental samples, with dilation of ER cisternae and increased phosphorylation of eukaryotic initiation factor 2 subunit α. Challenge of BeWo-NG with high glucose activated the same pathways, but this was as a result of acidosis of the culture medium rather than the glucose concentration per se. Addition of chemical chaperones 4-phenylbutyrate and tauroursodeoxycholic acid and vitamins C and E ameliorated the ER stress.. This is the first report of placental ER stress in GDM patients. Chemical chaperones and antioxidant vitamins represent potential therapeutic interventions for GDM.

Topics: Acidosis; Adult; Antioxidants; Ascorbic Acid; Blood Glucose; Blotting, Western; Cell Line; Diabetes, Gestational; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Female; Glucose; Humans; Phenylbutyrates; Phosphorylation; Placenta; Pregnancy; Taurochenodeoxycholic Acid; Unfolded Protein Response; Vitamin E

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Case-Control Studies; Diabetes, Gestational; Female; Free Radicals; Humans; Pregnancy; Sulfhydryl Compounds; Tocopherols; Uric Acid; Vitamin E; Young Adult

Fetuses from mothers with gestational diabetes are at increased risk of developing neonatal macrosomia and oxidative stress. We investigated the modulation of antioxidant status and circulating lipids in gestational diabetic mothers and their macrosomic babies and in healthy age-matched pregnant women and their newborns. The serum antioxidant status was assessed by employing anti-radical resistance kit (KRL; Kirial International SA, Couternon, France) and determining levels of vitamin A, C, and E and the activity of superoxide dismutase (SOD). Circulating serum lipids were quantified, and lipid peroxidation was measured as the concentrations of serum thiobarbituric acid-reactive substances (TBARS). As compared with non-diabetic mothers, gestational diabetic women exhibited decreased levels of vitamin E and enhanced concentrations of vitamin C without any changes in vitamin A. Vitamin A and C levels did not change in macrosomic babies except vitamin E whose levels were lower in these infants than in the newborns of non-diabetic mothers. Gestational diabetes mellitus (GDM) and macrosomia were also associated with impaired SOD activities and enhanced TBARS levels. Globally, total serum antioxidant defense status in diabetic mothers and their macrosomic babies was diminished as compared with control subjects. Triglyceride and cholesterol concentrations did not differ significantly between gestational diabetic and control mothers; however, macrosomia was associated with enhanced plasma cholesterol and triglyceride levels. These results suggest that human GDM and macrosomia are associated with downregulation of antioxidant status, and macrosomic infants also exhibit altered lipid metabolism.

Topics: Adult; Antioxidants; Ascorbic Acid; Cholesterol; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Lipids; Pregnancy; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Triglycerides; Vitamin A; Vitamin E

In Germany, urine analysis with dip sticks are used for screening of gestational diabetes. Our goal was to find the cut-off levels of glucose dip sticks and evaluate the influence of ascorbic acid on the result.. We took urine samples of 152 pregnant patients between 01/2004 and 10/2004. The glucose content of the urine was analyzed using several dip sticks (Combur10 Roche, Multistix 8SG Bayer, Diabur5000 Roche and by the hexokinase method. The ascorbic acid concentration of the specimen was determined.. Glycosuria test dip sticks have a good sensitivity and specificity of the expected positive/negative-reaction compared with the hexokinase method but showed a significant reduction of the color reaction at high concentrations of ascorbic acid.. High ascorbic acid concentrations cause a reduction in the color reaction of urine dip sticks. False-negative test stick measurements can appear in patients with low glycosuria. The rate of glycosuria shows high individual differences and dependent on the concentration of vitamin C. We conclude that dip sticks are not useful in prenatal management.

Topics: Adolescent; Adult; Ascorbic Acid; Diabetes, Gestational; False Negative Reactions; Female; Germany; Glucose; Glucose Tolerance Test; Glycosuria; Humans; Middle Aged; Pregnancy; Prenatal Care

To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM).. Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period.. Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2).. Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Diabetes, Gestational; Female; Humans; Pregnancy; Risk Factors

Antioxidants, particularly vitamin C (ascorbic acid), have the capacity to influence glucose tolerance. Modification of diet could reduce the likelihood of developing gestational diabetes mellitus.. In a prospective cohort study of pregnant women, we studied the association of maternal plasma ascorbic acid concentrations, measured at an average of 13 weeks' gestation, with subsequent risk of gestational diabetes. Maternal plasma ascorbic acid concentrations were determined using automated enzymatic procedures. Dietary vitamin C intake during the periconceptional period and early pregnancy was ascertained using a semiquantitative food frequency questionnaire. We fitted generalized linear models to derive estimates of relative risks and 95% confidence intervals (CIs).. Approximately 4% (n = 33) of 755 women who completed pregnancy developed gestational diabetes mellitus. Plasma ascorbic acid concentrations were inversely associated with the risk of gestational diabetes (P for trend = 0.023). After adjusting for maternal age, race, prepregnancy adiposity, parity, family history of type 2 diabetes, and household income, women with plasma ascorbic acid <55.9 micromol/L (lowest quartile) experienced a 3.1-fold increased risk of gestational diabetes (95% CI = 1.0 - 9.7) compared with women whose concentrations were > or = 74.6 micromol/L (upper quartile). Women who consumed <70 mg vitamin C daily experienced a 1.8-fold increased risk of gestational diabetes compared with women who consumed higher amounts (95% CI = 0.8 - 4.4).. If confirmed, our results raise the possibility that current efforts to encourage populations to consume diets rich in antioxidants, including vitamin C, could reduce the occurrence of gestational diabetes mellitus.

Topics: Adult; Ascorbic Acid; Cohort Studies; Diabetes, Gestational; Female; Humans; Linear Models; Maternal Welfare; Pregnancy; Pregnancy Outcome; Prospective Studies; Risk Factors; Surveys and Questionnaires; Washington

Diabetes teratogenicity seems to be related to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We have studied the mechanism by which antioxidants, such as vitamins C and E, reduce diabetes-induced embryonic damage. We therefore compared the antioxidant capacity of 10.5-day-old rat embryos and their yolk sacs cultured for 28h in diabetic culture medium with or without vitamins C and E.. The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml beta hydroxy butyrate (BHOB) and 10 microg/ml of acetoacetate were added. Rat embryos were also cultured in a diabetic medium with 25 microg/ml of vitamin E and 50 microg/ml of vitamin C. Control embryos were cultured in normal rat serum with or without vitamins C and E.. Decreased activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in the "diabetic" embryos and their yolk sacs, and reduced concentrations of low molecular weight antioxidant (LMWA) were found. Under these conditions we also found a decrease in vitamin C and vitamin E concentrations in the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver of embryos cultured in diabetic medium in comparison to controls. Following the addition of vitamins C and E to the diabetic culture medium, SOD and CAT activity, the concentrations of LMWA, the levels of vitamin C and E and the expression of SOD mRNA in the embryos and yolk sacs returned to normal.. Diabetic metabolic factors seem to have a direct effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes, reducing embryonic endogenous antioxidant defense mechanism. This in turn may cause a depletion of the LMWA, such as vitamins C and E. The addition of these vitamins normalizes the embryonic antioxidant defense mechanism, reducing the damage caused by the diabetic environment.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Catalase; Cells, Cultured; Chromatography, High Pressure Liquid; Diabetes, Gestational; Electrophysiology; Embryo, Mammalian; Female; In Situ Hybridization; Liver; Myocardium; Organ Culture Techniques; Pregnancy; Rats; RNA, Messenger; Spinal Cord; Superoxide Dismutase; Time Factors; Vitamin E

Diabetes during pregnancy is a pathological state causing many metabolic disorders, not only in carbohydrate metabolism. The aim of the study was to estimate the changes of lipids metabolism and changes of L-ascorbic acid serum concentration in pregnancy complicated by diabetes. In tested groups values of lipids metabolism parameters were lower in diabetic group compared to control group. The lowest mean values of concentration of total cholesterol, LDL cholesterol and triglycerides were found in gestational diabetes group, while the lowest mean value of HDL cholesterol concentration was found in pregestational diabetic group. The L-ascorbic acid mean values correlated negatively with total cholesterol concentrations, LDL cholesterol and triglycerides levels.

Topics: Adult; Ascorbic Acid; Carbohydrate Metabolism; Diabetes, Gestational; Female; Humans; Lipid Metabolism; Pregnancy