ascorbic-acid and Diabetic-Angiopathies

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Vascular endothelial dysfunction is an early pathophysiological precursor of cardiovascular disease. There is extensive evidence that hyperglycemia causes acute perturbations in endothelial function likely due to increases in oxidative damage. Interestingly, oscillating hyperglycemia may cause more damage than persistent hyperglycemia. Many, but not all, studies indicate that vascular endothelial dysfunction occurs early in the course of type 1 diabetes and is present even in adolescents. Ascorbic acid has been shown to diminish the acute effects of hyperglycemia on endothelial function in type 1 diabetes and in conjunction with euglycemia to restore endothelial function to normal values in adults with well-controlled diabetes. In vitro and in vivo animal evidence suggests potential benefit from two other small molecule antioxidants, nicotinamide and taurine. Early studies suggested that folate supplementation may improve endothelial function in adolescents with type 1 diabetes but this has not been confirmed by more recent studies. Epidemiological evidence suggests a possible role for vitamin D therapy although intervention studies in type 2 diabetes have yielded varying results and have not been done in type 1 diabetes. Further exploration of these and other compounds is clearly appropriate if we are to reduce cardiovascular risk in type 1 diabetes.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dietary Supplements; Disease Progression; Endothelium, Vascular; Folic Acid; Humans; Hyperglycemia; Oxidative Stress; Taurine; Vitamin D

Endothelial dysfunction due to hyperglycemia-induced oxidative damage is an important predictor of future cardiovascular risk in patients with type 1 diabetes mellitus (T1DM) and is present in adolescent T1DM. We hypothesized that combined treatment with the antioxidant vitamins C and E might improve endothelial function (EF) and other biochemical risk factors in adolescents with T1DM.. Open-label antioxidant supplementation was given for six weeks with endpoint measurements collected at baseline and study completion. Endpoints measured included EF and plasma measurements of biochemical endothelial risk.. Two males and 7 females were studied. Mean age was 12.9 ± 0.9 yrs; mean T1DM duration was 5.5 ± 2.5 yrs; mean BMI was 22.1 ± 3.8 kg/m(2); and mean hemoglobin A1c was 9.3 ± 1.1%. No differences were found for EF, high sensitivity CRP, total antioxidant capacity, adiponectin, or endothelial progenitor cells (EPCs) between before and after combined vitamin C and E therapy.. Our negative study results do not support previous findings of decreased oxidative damage, improved endothelial function, and increased vascular repair capacity with antioxidant therapy. Longer term studies may be needed to determine the effects, if any, of combined antioxidant therapy on EPCs, EF, and markers of micro- and macrovascular complications in T1DM.

Topics: Adolescent; Age Factors; Antioxidants; Ascorbic Acid; Biomarkers; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dietary Supplements; Drug Combinations; Endothelial Progenitor Cells; Endothelium, Vascular; Female; Humans; Inflammation Mediators; Male; Oxidative Stress; Treatment Outcome; Vasodilation; Vitamin E

Oxidative stress has been implicated in the pathogenesis of heart failure (HF). However, data on the association between antioxidant intakes and circulating levels and risk of incident HF in the older general population are limited. We have examined prospectively the associations between plasma vitamin C and E, dietary intakes of vitamin C and E, and incident HF.. Prospective study of 3919 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 11 years, in whom there were 263 cases with incident HF. Higher plasma vitamin C level was associated with significantly lower risk of incident HF in both men with and without previous myocardial infarction after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, and heart rate (hazards ratio [95% confidence interval], 0.81 [0.70, 0.93] and 0.75 [0.59, 0.97] for 1 SD increase in log vitamin C, respectively). Plasma vitamin E and dietary vitamin C intake showed no association with HF. High levels of dietary vitamin E intake (which correlated weakly with plasma vitamin E) were associated with increased risk of HF in men with no previous myocardial infarction even after adjustment (adjusted hazards ratio [95% confidence interval], 1.23 [1.06, 1.42] for 1 SD increase).. Higher plasma vitamin C is associated with a reduced risk of HF in older men with and without myocardial infarction. High intake of dietary vitamin E may be associated with increased HF risk. Primary intervention trials assessing the effect of vitamin C supplements on HF risk in the elderly are needed.

Topics: Aged; Ascorbic Acid; Diabetic Angiopathies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Assessment; Vitamin E

Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 microg Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Biomarkers; Cell Line; Chromium; Coordination Complexes; Cysteine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Dietary Supplements; Humans; Hypoglycemic Agents; Liver; Male; Monocytes; Organometallic Compounds; Oxidative Stress; Random Allocation; Rats; Rats, Zucker; Signal Transduction

To investigate the possibility of reversing endothelial dysfunction and inflammation by glucose normalization, antioxidants and insulin per se, in different subgroups of Type 1 diabetic patients.. Three subgroups of Type 1 diabetic patients were studied: patients within 1 month of diagnosis (subgroup 1); patients with approximately 5 years' disease duration and with glycated haemoglobin (HbA(1c)) 7.0% since diagnosis (subgroup 3). Participants underwent four procedures: 2-h hyperglycaemic clamp followed by: (A) 12 h near-normalization of blood glucose, with the addition of vitamin C during the last 6 h; (B) 12-h vitamin C and near-normalization of blood glucose for the last 6 h; (C) both vitamin C and near-normalization of blood glucose for 12 h; (D) hyperglycaemic-hyperinsulinaemic clamp for 12 h, with the addition of vitamin C during the last 6 h.. After 2 h of hyperglycaemia, markers of endothelial dysfunction, nitrotyrosine, 8-iso prostaglandin F2alpha, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, interleukin (IL)-6 and IL-18 were increased in all the subgroups. Levels were normalized, at all time points, by treatments A, B and C in the subgroups 1 and 2. In the third subgroup, levels were normalized only by the simultaneous normalization of blood glucose and vitamin C treatment. During treatment D, the levels were improved at 6 h in all the subgroups, but normalized at 12 h only after vitamin C in subgroups 1 and 2, but not in subgroup 3.. This study suggests that different subgroups of Type 1 diabetic patients react identically to acute hyperglycaemia and insulin, but differently to glucose normalization.

Topics: Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Male; Oxidative Stress; Young Adult

Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non-diabetic subjects.. Thirty-seven patients with DM + CAD, 17 patients with DM without CAD and 21 non-diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium-dependent dilation.. Baseline levels of IL-6 and TNF-alpha were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM-1, TNF-alpha and IL-6 in any of the groups.. Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.

Topics: Antioxidants; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Forearm; Humans; Hyperemia; Interleukin-6; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vasodilation

Alpha-tocopherol and ascorbic acid form a part of scavenger system influencing the level of oxidative stress in diabetes mellitus. The aim of this study was to evaluate serum concentrations of alpha-tocopherol and ascorbic acid in Type 1 and Type 2 diabetes mellitus and to compare them with the presence of vascular complications as well as with oxidative stress and endothelial dysfunction.. A total of 38 Type 1 and 62 Type 2 diabetic patients were subdivided into those with and without angiopathy. Serum alpha-tocopherol and ascorbic acid concentrations were estimated in all patients and in 38 healthy persons. Their results were compared with diabetes control, with oxidative stress measured by plasma malondialdehyde and with endothelial dysfunction estimated by serum N-acetyl-beta-glucosaminidase activity. In addition, the differences in biochemical variables were compared between patients with and without angiopathy.. Serum alpha-tocopherol related to the sum of cholesterol and triglyceride concentrations (AT/CHT ratio) was significantly lower in diabetic patients with macroangiopathy than in those without vascular changes (p<0.05). Serum ascorbic acid levels were significantly lower only in Type 2 diabetic patients with macroangiopathy as compared with healthy controls as well as with patients without vascular disease (p<0.01). Positive relationship was observed between serum alpha-tocopherol and cholesterol or triglyceride concentrations in both Type 1 and Type 2 diabetic patients. The presence of oxidative stress together with endothelial dysfunction measured by N-acetyl-beta-glucosaminidase activity was accompanied by lower AT/CHT ratio (p<0.005) in Type 2 diabetic patients.. Diabetic patients with proven angiopathy or with advanced oxidative stress and endothelial dysfunction have significantly lower AT/CHT ratio and ascorbic acid concentration in serum. Their low concentrations may participate at the increased level of oxidative stress in these individuals.

Topics: Acetylglucosamine; Adolescent; Adult; Antioxidants; Ascorbic Acid; Cholesterol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Lipids; Male; Malondialdehyde; Oxidative Stress; Serum Albumin; Triglycerides; Vitamin E

Accumulation of carbonyl derivatives of proteins (protein carbonyl) is taken as a biomarker of oxidative protein damage in aging and in various diseases. We detected protein carbonyls in situ in human diabetic arteriosclerotic tissues and characterized the formation of protein carbonyls. Protein carbonyls were identified in the thickened intima of arterial walls and co-localized with protein adducts formed by carbonyl amine chemistry between protein and carbonyl compounds derived from autoxidation of carbohydrates, lipids, and ascorbate, i.e. advanced glycation end products or glycoxidation products, such as carboxymethyllysine (CML) and pentosidine, and lipoxidation products, such as malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE). In vitro incubation of proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and pentosidine, and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and pentosidine, but not protein carbonyls. Schiff base inhibitors, (+/-)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylace tanilide and aminoguanidine, inhibited the production of protein carbonyls after incubation with ascorbate and arachidonate. The present study suggests that ascorbate and polyunsaturated fatty acids, but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases.

Topics: Arachidonic Acid; Arginine; Arteriosclerosis; Ascorbic Acid; Diabetic Angiopathies; Glucose; Glycation End Products, Advanced; Glycosylation; Humans; Lipid Peroxidation; Lipoproteins; Lysine; Malondialdehyde; Oxidation-Reduction; Oxidative Stress

Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes. We compared the radical-scavenging antioxidant activity of serum from 28 patients with insulin-dependent diabetes mellitus and 24 patients with non-insulin-dependent diabetes mellitus uncomplicated by vascular disease with age-matched non-diabetic control subjects. Patients with insulin-dependent diabetes had significantly reduced total antioxidant activity (320.2 +/- 11.3 vs. 427.5 +/- 19.2 mumol L-1; P < 0.001). This was attributable to lower urate (209.4 +/- 10.4 vs. 297.1 +/- 16.7 mumol L-1; P < 0.001) and vitamin C levels (63.6 +/- 6.0 vs. 87.5 +/- 4.9 mumol L-1; P < 0.01). Patients with non-insulin-dependent diabetes had lower total antioxidant activity than age-matched control subjects (433.8 +/- 25.4 vs. 473.9 +/- 30.2 mumol L-1; NS), reflecting lower urate (299.5 +/- 19.4 vs. 324.8 +/- 21.4 mumol L-1; NS) and vitamin C levels (38.6 +/- 5.7 vs. 58.5 +/- 5.3 mumol L-1; P < 0.05). Multiple regression analysis showed that urate, vitamin C and vitamin E were the major contributors to serum total antioxidant activity. These results show that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.

Topics: Adult; Antioxidants; Ascorbic Acid; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Free Radical Scavengers; Free Radicals; Humans; Male; Middle Aged; Sulfhydryl Compounds; Uric Acid; Vitamin E

To explore the hypothesis that a relationship exists between free radical activity and abnormalities in hemostasis in NIDDM.. The use of the total radical-trapping antioxidant parameter (TRAP) has very recently been proposed to explore the antioxidant property of a plasma and their mutual cooperation. In the present study, TRAP, vitamin E, vitamin C, vitamin A, uric acid, protein-bound SH (thiol) groups, fibrinogen, prothrombin fragments F1 + 2, and D-dimer have been evaluated in 46 NIDDM patients and 47 healthy matched control subjects.. In NIDDM patients, TRAP, vitamin A, SH groups, and uric acid were significantly reduced, whereas the level of vitamin E was significantly increased. Vitamin C was similar in the two groups. Fibrinogen, prothrombin fragment 1 + 2, and D-dimer were increased in diabetic patients. TRAP, but no single other antioxidant, had a strong inverse association with fibrinogen, prothrombin fragment 1 + 2, and D-dimer.. These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Prothrombin; Reference Values; Regression Analysis; Risk Factors; Thrombosis; Uric Acid; Vitamin A; Vitamin E

Diabetes is associated with increased oxidant stress. This may contribute to the development of diabetic macrovascular complications through increased oxidation of low-density lipoprotein (LDL), which is thought to be a crucial step in the development of atherosclerosis. The sulfonylurea gliclazide has been shown to have free radical-scavenging activity in vitro, but its effects on LDL oxidation, and these effects of other sulfonylureas, are unknown. To investigate this we studied the effects of in vitro supplementation with gliclazide 1 mumol/L on copper-induced oxidation of LDL isolated from 20 control subjects and 22 type II diabetic patients. The effects of 1 mumol/L vitamin C, a known water-soluble antioxidant, were studied simultaneously. The resistance to oxidation, expressed as the lag time between the addition of copper and commencement of oxidation, was significantly increased by both gliclazide and vitamin C, and the effect was similar for LDL from diabetic and control subjects. The baseline oxidation lag time was 63.4 +/- 2.1 minutes, and increased to 108 +/- 4.4 minutes with gliclazide and 88.7 +/- 5.6 minutes with vitamin C (P = .0001, baseline v either treatment). The increase in lag time with gliclazide of 70% +/- 3% was greater than the 30% +/- 5% increase with vitamin C (P < .0005). In a separate experiment, LDL isolated from eight control and 10 diabetic subjects was supplemented with 1 mumol/L gliclazide, glibenclamide, glipizide, and tolbutamide. For each LDL sample, all drugs were studied simultaneously and the oxidation lag time was compared against that of untreated LDL. Gliclazide increased the lag time from 53.7 +/- 2.4 minutes to 108.4 +/- 4.5 minutes (P = .0001). None of the other sulfonylureas had any effect on lag time. These findings demonstrate that gliclazide is an effective inhibitor of in vitro LDL oxidation, and in this respect, it is more potent on a molar basis than vitamin C. This antioxidant property of gliclazide was not shared by the other sulfonylureas studied.

Topics: Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Gliclazide; Glipizide; Glyburide; Humans; Hypoglycemic Agents; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Sulfonylurea Compounds; Tolbutamide

The relationship between serum ascorbic acid (AA) and diabetic macroangiopathy was studied. Fifty-six patients with noninsulin-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 atherosclerosis. 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 dehydroascorbic acid (DHAA) between patients and controls, nor were there any significant 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.

Topics: Adult; Aged; Albuminuria; Aorta; Apolipoprotein A-I; Apolipoproteins B; Arteriosclerosis; Ascorbic Acid; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Rheology; Thiobarbituric Acid Reactive Substances

Essential fatty acid metabolism is impaired by diabetes mellitus and gamma-linolenic acid rich treatments such as evening primrose oil correct deficits in nerve conduction and endoneurial blood flow in diabetic rats. Other mechanistically unrelated treatments, such as antioxidants and aldose reductase inhibitors have a similar effect and there may be positive interactions with multiple treatments. Our aim was to compare the efficacy of a novel essential fatty acid derivative, ascorbyl gamma-linolenic acid, with that of gamma-linolenic acid in correcting diabetic neurovascular deficits. Eight weeks of diabetes caused 20.4 and 48.2% reductions in sciatic motor conduction velocity and nutritive endoneurial blood flow, respectively. Treatment was given for the last 2 weeks with gamma-linolenic acid (100 mg.kg-1.day-1) either in pure form or as ascorbyl gamma-linolenic acid, an equivalent dose of ascorbate (21 mg.kg-1.day-1) or jointly with ascorbate and gamma-linolenic acid. Conduction velocity was corrected by 39.8, 87.4, 13.2 and 66.8% with gamma-linolenic acid, ascorbyl gamma-linolenic acid, ascorbate and gamma-linolenic acid plus ascorbate, respectively. Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4, 87.4, 13.2 and 65.7%. For the gamma-linolenic acid plus ascorbate combinatin, and especially for ascorbyl gamma-linolenic acid, the magnitude of correction for conduction velocity and blood flow was greater than expected for simple addition of ascorbate and gamma-linolenic acid, indicating a synergistic interaction. Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl gamma-linolenic acid may be a suitable candidate for clinical trials of diabetic neuropathy.

Topics: Animals; Ascorbic Acid; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Neuropathies; gamma-Linolenic Acid; Male; Motor Neurons; Neural Conduction; Rats; Rats, Sprague-Dawley; Sciatic Nerve

Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Erythrocytes; Humans; Insulin; Insulin Secretion; Vitamin E

To determine whether alteration in serum antioxidant status is related to the increased oxidative stress as a cause of diabetic angiopathy, we measured both the antioxidant activity (AOA) and total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in serum of children with insulin-dependent diabetes mellitus (IDDM). The AOA was measured as the ability to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, transferrin, and albumin as components of AOA; and ascorbic acid, uric acid, protein sulfhydryl, and alpha-tocopherol as components of TRAP. Serum AOA appeared to be decreased in the diabetics in relation to poor glycemic control, corresponding to the decrease in transferrin and albumin. Serum haptoglobin level was also decreased in the diabetics. Similarly, the directly measured TRAP value was decreased in the diabetic serum mainly due to the decreased contribution of unidentified chain-breaking antioxidants, despite the increase in ascorbic acid and alpha-tocopherol. The decrease in both types of antioxidant activity in the diabetic serum, as new findings, suggests that a defective serum antioxidant status contributes to the increased oxidative stress in IDDM.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Free Radical Scavengers; Free Radicals; Humans; Lipid Peroxidation; Male; Stress, Physiological; Uric Acid; Vitamin E

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 less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Ascorbic Acid; Blood Glucose; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Fructosamine; Hexosamines; Humans; Male; Reference Values

Plasma total ascorbate status measured by 2.4 dinitrophenyl hydrazine method showed that diabetics (N = 100) had significantly lower plasma total ascorbate compared with 45 age and sex matched non-diabetic controls; 0.34 +/- 0.16 mg/dl vs 0.68 +/- .06 mg/dl, P less than 0.001) regardless of presence or absence of retinopathy and irrespective of mode of treatment. The finding unique to this study was that plasma total ascorbate status in diabetics with retinopathy (0.19 +/- 0.07 mg/dl) was significantly lower than that of uncomplicated diabetics (0.49 +/- 0.06 mg/dl; P less than 0.001). Plasma Glucose had no correlation with plasma ascorbate levels and effect of duration of Diabetes Mellitus (DM) on ascorbate status in diabetics was ambiguous. Diabetics had abnormally fragile cutaneous capillaries detected by Hess test. The incidence of capillary fragility was more in patients with retinopathy. Hess test can be used as an easy and non-invasive test to assess plasma ascorbate status to detect microvascular involvement in DM. The experience of this study reflects that the two distinct microvascular lesions in diabetes, i.e. abnormal dermal capillary fragility and retinopathy may have a common link to ascorbic acid deficiency. An early switching on of the supplementation of ascorbic acid may retard the development of microvascular complications in diabetes.

Topics: Adult; Ascorbic Acid; Blood Glucose; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Retinopathy; Humans; Middle Aged

Recent evidence has suggested that diabetic microangiopathy is associated with increased free radical induced oxidative damage. Ascorbic acid (AA) is a free radical scavenger and using a specific HPLC method we have investigated its concentration and that of its oxidized metabolite dehydroascorbic acid (DHAA) in diabetic patients and matched normal controls. The findings have been related to the presence of microangiopathy and to glycaemic control. Ascorbic acid levels were significantly lower in diabetics (mean +/- SD 42.5 +/- 26.2 mumol/l) compared with controls (58 +/- 21 mumol/l p less than 0.02). Although there was no differences in DHAA levels between the groups the ratio DHAA/AA was increased in diabetics (0.72 +/- 0.8) compared with controls (0.4 +/- 0.2 p less than 0.05). There were no significant differences between insulin and non-insulin dependent patients in these measurements and there was no association with the presence of microangiopathy or poor glycaemic control. The plasma ratio DHAA/AA may be a reflection of increased oxidative stress and our results suggest that diabetics may be less able to prevent oxidative damage occurring due to their lower AA concentrations.

Topics: Ascorbic Acid; Dehydroascorbic Acid; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Fructosamine; Hexosamines; Humans; Middle Aged; Reference Values

Glucose in concentrations of 20 mg% (or greater) significantly inhibited 14C-labelled ascorbic acid (1.25 mg%) uptake in endothelial cells in the presence of insulin (1600 microU/ml). The absence of insulin also significantly reduced ascorbic acid uptake. Furthermore, this reduction could be exacerbated by glucose (40, 160 mg%) but not equimolar concentrations of fructose. Increased ascorbic acid concentrations (two-fold) in the absence of insulin (1) significantly enhanced uptake, and (2) reversed the inhibition of glucose. These findings support earlier reports that ascorbic acid uptake into the cell may be compromised by decreased insulin and/or increased extracellular glucose levels. Since previous animal studies have correlated experimental ascorbic acid deficiencies with atherogenic processes (presumably by altering glycosaminoglycan metabolism), the postulation that the "diabetic condition" (low insulin, hyperglycemia) accelerates the cellular changes leading to atherosclerosis by impairing ascorbic acid uptake into the vascular endothelium, may now be supported.

Topics: Animals; Ascorbic Acid; Cattle; Cells, Cultured; Diabetic Angiopathies; Endothelium; Glucose; Heart; Humans; Insulin; Myocardium

Topics: Ascorbic Acid; Aspirin; Calcium Dobesilate; Diabetic Angiopathies; Diabetic Retinopathy; Dipyridamole; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Pentoxifylline; Platelet Aggregation; Rutin; Thrombelastography; Vision, Ocular

Topics: Animals; Ascorbic Acid; Biological Transport; Carbohydrate Metabolism; Diabetic Angiopathies; Humans; Insulin; Nutritional Requirements

Topics: Aged; Ascorbic Acid; Diabetic Angiopathies; Female; Humans; Hyaluronic Acid; Leg Ulcer; Male; Middle Aged; Ointments; Rifampin; Vascular Diseases

Topics: Adipose Tissue; Alcohol Oxidoreductases; Animals; Aorta; Arteries; Ascorbic Acid; Carbon Dioxide; Carbon Isotopes; Chromatography, Paper; Decarboxylation; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Femoral Artery; Glucose; Glucuronates; Guinea Pigs; Humans; Male; Oxidoreductases; Rats; Rats, Inbred Strains; Species Specificity; Xylitol