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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that vitamin E may be an important preventative factor in the development and progression of atherosclerosis. In order to more clearly define the role of vitamin E in atherosclerosis, we measured vitamin E, conjugated diens, and lipid flurochromes, as well as cholesterol, triglycerides and phospholipid in arterial and venous tissue of 83 patients. Serum cholesterol and triglyceride levels were significantly higher (P < 0.05) in patients with aortic occlusive (AIOD) and aneurysmal (AAA) disease than in control organ donors (OD). Tissue cholesterol concentrations were significantly elevated in AAA tissue when compared to OD and tissue from patients with peripheral occlusive disease (POD). Tissue from patients with AIOD contained greater concentrations of phospholipid (PL) than were measured in patients with POD and in OD. Vitamin E concentrations were highest in POD tissue and approximately 3.0, 2.0, and 1.6 fold greater than OD, AIOD and AAA tissue respectively. Diene conjugates and lipid flurochromes, measures of early and intermediate products of lipid peroxidation, were markedly elevated in all diseased arterial tissue compared to controls. There were no significant differences in tissue or serum lipid levels between saphenous vein (SVBG) and diseased vein grafts (DVG). However, conjugated diene concentrations were elevated in DVG compared to SVBG. Vitamin E levels were significantly elevated in diseased arterial and venous tissue (AIOD, AAA, POD, DVG) removed from patients with diabetes (P = 0.013) and hypertension (P = 0.049) compared to those without these risk factors. Diabetes was the only risk factor associated with significantly increased (P = 0.005) levels of vitamin E when only data from atherosclerotic arterial tissue (AAA, POD, AIOD) were analyzed. These preliminary data provide additional evidence of altered vitamin E metabolism and free radical processes in the tissues of patients with various manifestations of atherosclerosis.
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PMID:Vitamin E levels in human atherosclerotic plaque: the influence of risk factors. 890 54

Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders.
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PMID:Neuroprotection by the metabolic antioxidant alpha-lipoic acid. 895 63

1. Since oxygen free radicals are directly involved in a variety of pathologies such as atherosclerosis, diabetes mellitus, inflammation and/or when a deficit of defences of the organism against radicals occurs, we developed a suitable and simple method to determine both the erythrocyte sensitivity to an oxidative stress and plasma antioxidant protective capacity. 2. This test is based on the introduction at 37 degrees C of a radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), within an erythrocyte suspension leading to a membrane alteration and ultimately to haemolysis. The latter can be quantified by determining the lacticodeshydrogenase activity released in the medium. The erythrocyte sensitivity to haemolysis and the volume of plasma inhibiting 50% of the haemolysis were determined. 3. Intra-assay CVs were 1.9% for erythrocyte sensitivity to oxidative stress and 3.4% for inhibitory 50% plasma volume. Inter-assay CVs for both erythrocyte sensitivity and inhibitory 50% plasma volume were 4%. 4. The reliability of this method was assessed and applied to test the protective effect of vitamin E, a well known antioxidant agent, in six healthy volunteers. Two weeks after daily administration of 500 mg of vitamin E, the mean plasma vitamin E concentration increased by 41% from 10.7 +/- 2.0 mg l-1 before treatment (P < 0.05). As the vitamin E concentration increased, the mean inhibitory 50% plasma volume and the percentage of haemolysed erythrocytes decreased respectively by 29% from 3.35 +/- 0.5 microliter (P < 0.05) and 18% from 71.5 +/- 3.8% (P < 0.05). No significative variation of these parameters was observed in six adult men without vitamin E supplementation. 5. Thus, this global and simple test permits an antioxidant status evaluation of a patient. It can be applied to various pathologies and allows the potency of new antioxidant molecules to be evaluated.
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PMID:A method for simultaneous determination of plasma and erythrocyte antioxidant status. Evaluation of the antioxidant activity of vitamin E in healthy volunteers. 897 29

The study was designed to evaluate whether the antioxidant nutrients selenium, vitamin A, and vitamin E are associated with alterations of blood viscosity in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). We assessed selenium concentrations in plasma and red blood cells (RBC), glutathione peroxidase activity in RBC, vitamin A and vitamin E, and the viscosity of whole blood and plasma in 20 patients with IDDM and 20 sex, age and body mass index-matched healthy controls. While selenium was not altered in plasma in IDDM, it was markedly decreased in RBC of IDDM (1.24 +/- 0.32 vs 0.92 +/- 0.38 mumol l-1, p = 0.006) correlating negatively with the elastic and viscous component of whole blood viscosity. Plasma viscosity increased with stage of retinopathy. Mean glutathione peroxidase activity in RBC was reduced in IDDM (5.78 +/- 0.77 vs 5.13 +/- 1.03 U gHb-1, p = 0.029). In IDDM with normal renal function (creatinine < or = 97.2 mumol l-1, no albuminuria) vitamin A was significantly reduced (1.26 +/- 0.62 vs 1.89 +/- 0.56 mumol l-1, p = 0.005). Vitamin A levels increased with impaired renal function. They strongly correlated with plasma creatinine (r = 0.86, p < 0.001) and plasma viscosity (r = 0.71, p = 0.001). However, in vitro experiments with different vitamin A plasma concentrations indicated that this particular correlation may not represent a causal one. No changes in vitamin E were found in IDDM. We conclude that reduced selenium concentrations in RBC contribute to impaired haemorheology in IDDM patients. Plasma viscosity was not affected by the plasma concentrations of vitamins A and E.
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PMID:Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus. 897 86

Experimental work from our laboratory has confirmed the protective power of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, the diabetic cataract too has been partially prevented. The protection slightly increased, when vanadium was administered in combination with vitamin E. This investigation has introduced a combination of Na3VO4 plus the lazaroid U-83836E, a liposoluble antioxidant much more efficacious than tocopherol, in order to improve the insufficient protection when vitamin E was used. Male Wistar rats, rendered diabetic with STZ, were treated for 12 weeks with Na3VO4 in drinking water, U-83836E carried by the food, or both. The most significant metabolic parameters (food and fluid intake, diuresis and excreted feces) were studied monthly by means of metabolic cages. Body weight, glycemia, glycosuria and proteinuria were also recorded. At week 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled. Circulation glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG) and fluorescent peroxides were evaluated at the end of the experiment. After the first month of treatment U-83836E improved significantly the protective effect of vanadate alone on polydipsia and polyuria, but more efficiently on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was observed also on HbA1c, NAG and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered per os, in a non invasive manner.
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PMID:[Protective effect on nephropathy and on cataract in the streptozotocin-diabetic rat of the vanadium-lazaroid combination]. 899 28

Glycosylation (glycation) of proteins is a major complication of hyperglycemia in diabetes. This study has examined the effect of hydrogen peroxide (H2O2) and tertiary-butylhydroperoxide (TBH) and vitamin E (E) on glycation of hemoglobin (GHb). The RBC (15%) in phosphate-buffered saline were treated with 5-50 mM glucose (G) with and without H2O2 or TBH at 37 degrees C for 1-3 d. Glycation of hemoglobin was assessed by GHb formation using Glyc-affinity columns. There was an increase in the GHb formation with increasing G concentrations. GHb formation increased significantly in the presence of H2O2 at all G concentrations. The increase in GHb was blocked when RBC were pretreated with E. E also inhibited formation of malondialdehyde (MDA), an end product of lipid peroxidation, as assessed by the thiobarbituric acid reactivity. Similar increase in the GHb formation was observed when TBH was used instead of H2O2 to induce oxidant stress to the RBC. To examine any role of MDA per se in increased glycation, RBC were treated ex vivo with and without exogenous standard MDA. GHb formation was significantly higher with G-MDA in contrast to G alone. Thus, increased oxygen radicals activity can initiate per-oxidation of lipids and MDA accumulation, which in turn, can stimulate glycation of proteins in diabetes. E can block the glycation of proteins by inhibiting MDA formation.
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PMID:The effect of oxygen radicals metabolites and vitamin E on glycosylation of proteins. 901 22

N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage.
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PMID:Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. 902 79

Because d-alpha-tocopherol (vitamin E) has been shown to decrease diacylglycerol (DAG) levels and prevent the activation of protein kinase C (PKC), which is associated with retinal and renal dysfunctions in diabetes, the study presented here characterized the effect of d-alpha-tocopherol treatment to prevent glomerular hyperfiltration and increased albuminuria as well as PKC activities in streptozotocin (STZ)-induced diabetic rats. Two weeks after the induction of diabetes, total DAG content and PKC activity in glomeruli were significantly increased in diabetic rats by 106.4 +/- 16.8% and 66.4 +/- 8.4%, respectively, compared with control rats. Intraperitoneal injection of d-alpha-tocopherol (40 mg/kg of body weight) every other day prevented the increases in total DAG content and PKC activity in glomeruli of diabetic rats. Glomerular filtration rate (GFR) and filtration fraction (FF) were significantly elevated to 4.98 +/- 0.34 mL/min and 0.36 +/- 0.05, respectively, in diabetic rats, compared with 2.90 +/- 0.14 mL/min and 0.25 +/- 0.02, respectively, in control rats. These hemodynamic abnormalities in diabetic rats were normalized to 2.98 +/- 0.09 mL/min and 0.24 +/- 0.01, respectively, by d-alpha-tocopherol. Albuminuria in 10-wk diabetic rats was significantly increased to 9.1 +/- 2.2 mg/day compared with 1.2 +/- 0.3 mg/day in control rats, whereas d-alpha-tocopherol treatment improved albumin excretion rate to 2.4 +/- 0.6 mg/day in diabetic rats. To clarify the mechanism of d-alpha-tocopherol's effect on DAG-PKC pathway, the activity and protein levels of DAG kinase alpha and gamma, which metabolize DAG to phosphatidic acid, were examined. Treatment with d-alpha-tocopherol increased DAG kinase activity in the glomeruli of both control and diabetic rats, by 22.6 +/- 3.6% and 28.5 +/- 2.3% respectively, although no differences were observed in the basal DAG kinase activity between control and diabetic rats. Because immunoblotting studies did not exhibit any difference in the protein levels of DAG kinase alpha and gamma, the effect of d-alpha-tocopherol is probably modulating the enzyme kinetics of DAG kinase. These findings suggest that the increases in DAG-PKC pathway play an important role for the development of glomerular hyperfiltration and increased albuminuria in diabetes and that d-alpha-tocopherol treatment could be preventing early changes of diabetic renal dysfunctions by normalizing the increases in DAG and PKC levels in glomerular cells.
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PMID:Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol. 907 11

To evaluate the role of both oxidation and inflammation in atherosclerosis, we compared LDL oxidizability, in vivo lipid and cholesterol oxidation, and basal and lipopolysaccharide (LPS)-stimulated production of various cytokines in normolipidemic patients with diabetes mellitus (DM: n = 11), cigarettes smokers (n = 14). In addition, the effects of vitamin E (600 I.U./day for 4 weeks) on these parameters were evaluated. Initial LDL oxidation characteristics before and after vitamin E were identical in the 3 groups. Plasma thiobarbituric acid reactive substances were higher in DM and smokers versus controls (0.77 +/- 0.22, 0.74 +/- 0.14 versus 0.62 +/- 0.10 mumol malondialdehyde equivalents/l, respectively; P versus controls < 0.05) and normalized after vitamin E supplementation. Total plasma oxysterols were higher in smokers versus controls (354 +/- 104 versus 265 +/- 66 nmol/l, P < 0.05) and unaffected by vitamin E. The basal and LPS-stimulated levels of interleukin-1 beta and tumour necrosis factor alpha (TNF alpha) and the basal level of interleukin-1-receptor antagonist (IL-1RA) were identical for the 3 groups. LPS-stimulated IL-1RA was higher in DM versus controls (10.7 +/- 2.0 versus 8.1 +/- 1.7 pmol/l, P < 0.05). After vitamin E, TNF alpha dropped in controls and smokers, and IL-1RA in smokers only. Results suggest increased in vivo oxidative stress and inflammation in DM and smoking, which is partly overcome by vitamin E.
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PMID:Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and cigarette smoking: effects of vitamin E treatment. 910 58

An association between excess oxygen radical activity and disturbed embryogenesis in diabetic pregnancy has been suggested. In the present study, the protective capacity of vitamin E with different treatment regimens was investigated in early and late pregnancy of streptozotocin-induced diabetic rats. Daily gavaging of 0.2 g/kg or 0.8 g/kg of vitamin E exerted moderate protective effects. In contrast, treatment with a diet enriched with 2% (wt/wt) of vitamin E, yielding an approximate daily dosage of 2 g/kg of vitamin E, clearly restored both embryonic and fetal morphology. High-performance liquid chromatography measurement showed that maternal diabetes decreased embryonic content of vitamin E. When pregnant diabetic animals were supplemented with vitamin E, increased concentrations of the vitamin were found in maternal, embryonic, and fetal tissues. Thus, despite marked accumulation of vitamin E in maternal tissues, the compound apparently reached the conceptus. Thiobarbituric acid reactive substances (TBARS) were estimated as a measure of lipid peroxidation, and no changes were observed in maternal tissue, embryonic tissue, placenta, and fetal brain in the untreated diabetic group. In contrast, a fivefold increase of TBARS was found in fetal liver, a rise that was reduced with vitamin E treatment of the diabetic pregnant rats and completely normalized with 2% vitamin E in the diet. Congenital malformations caused by experimental diabetes can be prevented by antioxidants in vivo. These findings further corroborate the notion that an imbalance in the metabolism of free oxygen radicals is involved in the embryonic maldevelopment of diabetic pregnancy, and suggest a direction for prophylactic treatment in the future.
Diabetes 1997 Jun
PMID:Vitamin E decreases the occurrence of malformations in the offspring of diabetic rats. 916 79


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