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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.
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PMID:Absence of increased susceptibility of LDL to oxidation in type 1 diabetics. 886 59

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

Increased free radical-mediated lipoprotein oxidation may contribute to the increased prevalence of atherosclerosis in non-insulin dependent diabetes. We have determined levels of malondialdehyde (MDA) and 7-ketocholesterol, a specific indicator of free radical-mediated oxidation of lipoprotein cholesterol, in serum in very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein (LDL) and high density lipoprotein fractions of serum separated by sequential flotation ultracentrifugation. Four groups of male subjects were studied: normal controls, diabetic patients with no evidence of microvascular complications or macrovascular disease, diabetic and non-diabetic patients with peripheral vascular disease (PVD). MDA was increased in vascular disease patients (diabetic 4.5 (3.7-5.8), non-diabetic 4.4 (3.2-5.7) mumol/l, median (2.5-97.5 percentiles)) than controls (3.6 (2.9-5.0) mumol/l) (P < 0.01), but was not increased in uncomplicated diabetic patients (3.8 (3.0-4.8) mumol/l). There were no significant differences in 7-ketocholesterol concentration in LDL, but calculated total 17-ketocholesterol was lower in non-diabetic vascular patients than controls (P < 0.01). Vitamin C concentration was reduced in diabetic and non-diabetic patients with vascular disease. No significant difference in concentration of vitamin E or A was found. In six normal subjects the concentration of MDA was low in lipoproteins separated by ultracentrifugation but high in the residue following lipoprotein fractionation (70-80% total serum MDA). In conclusion, the concentration of MDA by the thiobarbituric acid assay in untreated serum may not reflect free radical damage to lipoproteins. There was no evidence of increased lipoprotein oxidation using 7-ketocholesterol in NIDDM or PVD.
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PMID:7-ketocholesterol, a specific indicator of lipoprotein oxidation, and malondialdehyde in non-insulin dependent diabetes and peripheral vascular disease. 910 Oct 96

Recent studies have suggested that elevated cellular lipid peroxidation may play a role in the development of cellular dysfunction and other complications of diabetes. People with type 1 diabetes frequently encounter elevated levels of the ketone bodies acetoacetate (AA), beta-hydroxybutyrate (BHB), and acetone (ACE). This study was undertaken to test the hypothesis that ketosis might increase lipid peroxidation and lower glutathione (GSH) levels of red blood cells (RBCs) in diabetic patients. This study demonstrates that incubation of AA with normal RBCs in phosphate-buffered saline (37 degrees C for 24 h) resulted in marked GSH depletion, oxidized glutathione accumulation, hydroxyl radical generation, and increased membrane lipid peroxidation. Increases in oxygen radicals and lipid peroxidation and depletion of GSH in RBCs were not observed with BHB or ACE treatments. Similarly, there was a significant generation of superoxide ion radicals even in a cell-free buffer solution of AA, but not in that of BHB. The presence of BHB together with AA did not influence the capacity of AA to generate oxygen radicals in a cell-free solution or the increase in lipid peroxidation of RBCs incubated with AA. The antioxidants vitamin E and N-acetylcysteine (NAC) blocked increase in lipid peroxidation in AA-treated RBCs. To examine the effects of ketone bodies in vivo, studies were performed that showed a significant decrease in GSH and an increase in lipid peroxidation levels in RBCs of hyperketonemic diabetic patients, but not in normoketonemic type 1 diabetic patients, when compared with age-matched normal subjects. This study demonstrates that elevated levels of the ketone body AA can increase lipid peroxidation and lower GSH levels of RBCs in people with type 1 diabetes.
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PMID:Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients. 1048 Jun 18

Preceding the onset of type 1 diabetes mellitus, pancreatic islets are infiltrated by macrophages secreting interleukin-1beta (IL-1beta) which induces beta-cell apoptosis and exerts inhibitory actions on islet beta-cell insulin secretion. IL-1beta seems to act chiefly through induction of nitric oxide (NO) synthesis. Hence, IL-1beta and NO have been implicated as key effector molecules in type 1 diabetes mellitus. In this paper, the influence of endogenously produced and exogenously delivered NO on the regulation of cell proliferation, cell viability and discrete parts of the stimulus-secretion coupling in insulin-secreting RINm5F cells was investigated. Because vitamin E may delay diabetes onset in animal models, we also investigated whether tocopherols may protect beta-cells from the suppressive actions of IL-1 and NO in vitro. To this end, the impact of NO on insulin secretory responses to activation of phospholipase C (by carbamylcholine), protein kinase C (by phorbol ester), adenylyl cyclase (by forskolin), and Ca(2+) influx through voltage-activated Ca(2+) channels (by K(+)-induced depolarization) was monitored in culture after treatment with IL-1beta or by co-incubation with the NO donor spermine-NONOate. It was found that cell proliferation, viability, insulin production and the stimulation of insulin release evoked by carbamylcholine and phorbol ester were impeded by IL-1beta or spermine-NONOate, whereas the hormone output by the other secretagogues was not altered by NO. Pretreatment with gamma-tocopherol (but not alpha-tocopherol) afforded a partial protection against the inhibitory effects of NO, whereas specifically inhibiting inducible NO synthase with N-nitro-L-arginine completely reversed the IL-1beta effects. In contrast, inhibiting guanylyl cyclase with ODQ (1H-[1,2, 4]oxadiazolo[4,3-alpha]-quinoxaline-1-one) or blocking low voltage-activated Ca(2+) channels with NiCl(2) failed to influence the actions of NO. In conclusion, our data show that NO inhibits growth and insulin secretion in RINm5F cells, and that gamma-tocopherol may partially prevent this. The results suggest that phospholipase C or protein kinase C may be targeted by NO. In contrast, cGMP or low voltage-activated Ca(2+) channels appear not to mediate the toxicity of NO in these cells. These adverse effects of NO on the beta-cell, and the protection by gamma-tocopherol, may be of importance for the development of the impaired insulin secretion characterizing type 1 diabetes mellitus, and offer possibilities for intervention in this process.
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PMID:gamma-tocopherol partially protects insulin-secreting cells against functional inhibition by nitric oxide. 1103 27

This study evaluated several parameters related to mitochondrial function and oxidative stress in streptozotocin (STZ)-treated rats, a model of type 1 diabetes. For this purpose, the respiratory indexes (RCR and ADP/O ratio), mitochondrial transmembrane potential (DeltaPsim), repolarization lag phase, repolarization level, mitochondrial enzymatic activities, ATP and malondialdehyde (MDA) levels, reduced glutathione (GSH), vitamin E and cardiolipin contents were determined in rat brain mitochondria isolated after 4 and 9 weeks after STZ treatment. Brain mitochondria isolated from citrate (vehicle)-treated Wistar rats were used as control. We observed that STZ-induced diabetes did not substantially affect brain mitochondrial function. Instead, 4-week diabetic rats presented higher mitochondrial respiratory chain enzymatic activities, especially succinate-cytochrome C reductase activity, compared to 4-week control rats. In 9-week diabetic rats, only a significant decrease in cardiolipin content was observed; however, a significant increase in mitochondrial GSH content occurred. All other parameters analysed remained statistically unchanged. From these results, we conclude that STZ-induced diabetes did not promote brain mitochondrial dysfunction, suggesting that oxidative stress associated with type 1 diabetes is not directly related to mitochondrial dysfunction, but probably is related to extramitochondrial factor(s).
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PMID:Effect of streptozotocin-induced diabetes on rat brain mitochondria. 1496 73

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73

Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect.
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PMID:Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide. 1549 67

In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.
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PMID:Antioxidant status in alcohol-related diabetes mellitus in Beninese subjects. 1637 21

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.
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PMID:Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes. 1638 9


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