Plasma ascorbate concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitus

Stanková, L; Riddle, Matthew C.; Larned, Joshua; Burry, Kenneth A.; Menashe, D.; Hart, Jean; Bigley, Robert H.

doi:10.1016/0026-0495(84)90197-5

Cited by 105 publications

(51 citation statements)

References 20 publications

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“…The lack of a significant difference in DHA concentrations between control subjects and diabetic patients is in accord with previous studies [32,33], but contrary to earlier reports of elevated DHA in Indian diabetic patients [4,34]. This discrepancy is unlikely to be due to differences in type or severity of diabetes since DHA concentrations (without ascorbic acid supplementation) are not related to treatment, duration of illness or blood glucose concentrations [4].…”

Section: Discussionsupporting

confidence: 87%

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

et al. 1991

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Summary. Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1+19.3 vs 55.6 _+ 20.0, p < 0.01, vs 82.9 _+ 30.9 gmol/1, p < 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87+0.46 vs 0.61 + 0.26, p < 0.01, vs 0.38 + 0.14, p < 0.001). At three weeks, ascorbate concentrations rose in all groups (p < 0.0001) and was maintained in control subjects (151.5 + 56.3 ~tmol/1), but fell in both diabetic groups by six weeks (p<0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p < 0.0001) but rose again in the diabetic groups by six weeks (p < 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p < 0.05). No significant changes were observed in fructosamine concentrations in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.Key words: Ascorbic acid, dehydroascorbic acid, diabetes mellitus, free radical activity, oxidative stress.Reduced levels and altered metabolic turnover of ascorbic acid (AA, vitamin C) have been reportedin severaltissues in experimen tally induced diabetes [1-3] and in diabeticpatients [4]. There are reports that high dose vitamin C regimens are associated with reversal of early signs of retinopathy [5] and normalisation of capillary strength in diabetes mellitus [6]. In the elderly non-diabetic population AA is often deficient and may be correctable by supplementation [7] -this problem might be of particular significance in elderly diabetic patients who are reported to show more rapid progress of some diabetic complications [8].Ascorbic acid functions as an important component of cellular defence against oxygen toxicity and lipid peroxidation caused by free radical mechanisms [9,10]. During scavenging of free radicals it is converted to dehydroascorbic acid, DHA, in serum and in the mitochondrial fractions of various tissues [11]. It is also a co-factor in the biosynthesis and post-translational modification of collagen...

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Section: Discussionsupporting

confidence: 87%

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

et al. 1991

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“…Numerous reports have found decreased levels of AA in diabetics (21)(22)(23)(24)(25), and similar results were obtained in the present study. Also, numerous cases showing reduced AA concentration inside the cells of diabetics with a high blood glucose level have been reported (22,(26)(27)(28)(29)(30).…”

Section: Resultssupporting

confidence: 92%

“…Also, numerous cases showing reduced AA concentration inside the cells of diabetics with a high blood glucose level have been reported (22,(26)(27)(28)(29)(30). DHAA, the oxidized form of AA, is quickly taken up by the cell (31,32), and is instantly reduced to AA, inside the cell.…”

Section: Resultsmentioning

confidence: 99%

Decrease of Serum Ascorbic Acid Concentrations in Patients with Diabetic Macroangiopathy.

Nagano

Kurokawa

Ebara

et al. 1996

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe relationship between serum ascorbic acid (AA) and diabetic macroangiopathy was studied. Fifty-six patients with non insulin-dependent diabetes mellitus were examined, together with 20 healthy controls matched for age against the diabetes patients. Aortic pulse wave velocity (PWV) was taken as an index of the severity of ather osclerosis. The level of serum AA in diabetic patients was significantly lower than that of the controls. Among the diabetic groups, those with elevated PWV levels by age demonstrated a significant drop in AA. No significant differences were seen in the level of serum dehydroascrobic acid (DHAA) between patients and controls, nor were there any signifi cant differences among patient groups. The concentration of serum AA was inversely related to the risk factors of atherosclerosis, such as body mass index, Apo B/Apo A-I ratio, thiobarbituric acid-reactive substances (TBARS), and microalbumin in urine. It was inferred from these findings that the depletion of serum AA was apparent in diabetics with advanced atherosclerosis.

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“…Moreover, bioavailability of AA also depends on amounts of transporting proteins and their binding affinity (85) which is impaired in chronic conditions such as diabetes. It is known that cellular uptake of AA is orchestrated by blood levels of both glucose and insulin (86,87). Therefore, the presence of hyperglycemia in diabetic subjects could increase the urinary loss of this vitamin and subsequently results in lower levels of AA in diabetics (88).…”

Section: Discussionmentioning

confidence: 99%

Influence of Ascorbic Acid Supplementation on Type 2 Diabetes Mellitus in Observational and Randomized Controlled Trials; A Systematic Review with Meta-Analysis

et al. 2015

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-Purpose.There are controversial data regarding the beneficial effects of ascorbic acid (AA) supplementation in type 2 diabetes mellitus (T2DM). In this systematic review, we aimed to criticize the current relevant data from both observational and randomized controlled trials (RCTs). Methods. All observational and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics, published before January 2013, were included. To obtain all related studies Google Scholar, PubMed, Scopus, IranMedex, and Magiran web databases were searched. Exclusion criteria were animal studies, and studies conducted in Type 1 DM, children or pregnant women. Main outcome measures were fasting blood sugar (FBS), and glycated hemoglobin (HbA1c). According to degree of heterogeneity, fixed or random effect models were employed. Meta-analyses were done using Stats Direct software, version 3.0.97. The quality of included articles and publication bias were also assessed. Results. We selected 38 articles; 26 observational studies and 12 RCTs. Due to severe methodological heterogeneity in all observational studies and some of RCTs, we could pool data from only 5 RCTs in a meta-analysis. Single intake of AA versus placebo showed a significant effect on FBS; with the standardized mean difference (SMD): -20.59, 95% confidence intervals (95% CI): -40.77 to -0.4 (p= 0.04), but non-significant effect on HbA1c; SMD: -0.46, 95% CI: -1.75 to 0.84 (p= 0.4). Effect of other antioxidants with/without AA supplementation on FBSwere nonsignificant; SMD: -4.26 (p= 0.8), and SMD: -12.04 (p= 0.3), respectively. Also, their effect on HbA1c was non-significant; SMD: 0.53 (p= 0.11), and SMD: 0.28 (p= 0.34), respectively. Conclusions. Our study supports the positive effect of AA in reduction of FBS in diabetics, however, due to insufficient evidence ragarding long term safety of AA supplementation and limited number of RCTs, the long term use of this vitamin for its anti-diabetic properties cannot be strongly recommended.

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Plasma ascorbate concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitus

Cited by 105 publications

References 20 publications

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

Decrease of Serum Ascorbic Acid Concentrations in Patients with Diabetic Macroangiopathy.

Influence of Ascorbic Acid Supplementation on Type 2 Diabetes Mellitus in Observational and Randomized Controlled Trials; A Systematic Review with Meta-Analysis

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