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

The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
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PMID:From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis. 1183 7

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
Diabetes Obes Metab 2002 Jan
PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

Vitamin E, an antioxidant, improves insulin sensitivity through the suppression of conventional PKC in vascular smooth muscle cells. It has been reported that vitamin E reduces platelet aggregation through the suppression of PKC alpha and beta (Diabetes 47 (1998) 1494). On the other hand, 1 alpha,25-dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may subsequently cause insulin resistance. Against this background, we examined the effect of vitamin E and 1,25D3 on PKC beta and PKC zeta/lambda activities in vitro and 10 nM insulin-induced glucose uptake in rat adipocytes. In vitro PKC beta activity of adipocytes was slightly decreased by the addition of 1 microM vitamin E, but not PKC zeta/lambda activity. In contrast, a 10-1000 nM 1,25D3 dose responsively activated PKC beta activity of adipocytes (ED 50%, 10 nM), but not PKC zeta/lambda activity. Pretreatment with 1 microM vitamin E for 60 min did not improve the insulin-induced glucose uptake. On the other hand, pretreatment with a 10-1000 nM 1,25D3 dose responsively suppressed insulin-induced glucose uptake. Moreover, 1,25D3 increased membrane-associated PKC beta immunoreactivity for 60 min, but no additional increase in membrane-associated PKC beta immunoreactivity during treatment with insulin was observed. These results suggest that 1,25D3 reduces insulin-induced glucose uptake via activation of PKC beta, but not vitamin E in rat adipocytes.
Diabetes Res Clin Pract 2002 Mar
PMID:Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. 1185 93

There is a clearly documented link between diabetic complications and lipid peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous antioxidants and increases generation of free radicals. The present study was carried out to compare the protective effects of melatonin and vitamin E against streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100 microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low density lipoprotein (LDL) levels were increased in STZ group while both melatonin and vitamin E injection caused a significant decrease in the levels of all these parameters. The lipid lowering effect of melatonin was greater than that of vitamin E. Melatonin caused a significant decrease in brain, liver and kidney tissue malondialdehyde (MDA) levels which were increased because of STZ-induced diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat tissues, but the effect of melatonin was more potent than that of vitamin E. Furthermore, treatment of diabetic rats with melatonin increased brain and kidney glutathione peroxidase (GSH-Px) activity to the levels below that of control rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain and kidney than melatonin whereas it was more potent than melatonin in liver. In summary, melatonin prevents many diabetic complications by reducing oxidative stress and protects organisms from oxidative damage and dyslipidemia. Considering the much lower molar concentration of melatonin compared with vitamin E, melatonin seems to be a more potent antioxidant, especially in the brain and kidney.
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PMID:Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. 1198 91

The aim of this study was to determine whether there are any disturbances of red/ox balance in the renal cortex of rats during the course of experimental diabetes. In the renal cortex of rats with streptozotocin-induced diabetes, the activity of superoxide dismutase (SOD) isoenzymes, glutathione peroxidase (GSH-Pox). glutathione S-transferase (GST) and glutathione reductase (GSH-RED) was measured in the 5th, 10th and 15th weeks of diabetes. Free radical cell damage was assessed on the basis of malonyldialdehyde (MDA) concentration. The influence of lipophilic antioxidant vitamin E on these analytes was also studied. An increase in MDA concentration in the 10th and 15th weeks of diabetes correlated significantly with plasma glucose concentration (r=0.47; p<0.001). Moreover, MDA concentration was influenced by time (+); p<0.001, diabetes (+); p<0.001, vitamin E (-) p<0.001 (ANOVA). Plasma creatinine concentration in rats was elevated by diabetes (p<0.001), whereas vitamin E decreased the concentration (p<0.05). Vitamin E lowered the activity of GSHPox (p<0.001) and GST (p<0.01) (ANOVA). Our results indicate that during experimental diabetes, disturbances of red/ox balance lead to disturbance in renal function manifested as increased creatinine blood concentration. We suggest that oral supplementation of vitamin E protects the renal cortex of rats during experimental diabetes.
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PMID:Evidence of oxidative stress in the renal cortex of diabetic rats: favourable effect of vitamin E. 1200 18

Oxidative stress plays an important role in the chronic complications of insulin-dependent diabetes mellitus (IDDM). Hyperketonemia, as well as hyperglycemia, is involved in the generation of oxygen-free radicals. We have studied the degree of oxidative stress in six patients before, during, and after correction of diabetic ketoacidosis (DKA) by determining the plasma ratios of C20 and C18 fatty acids to C16 fatty acids in the cholesteryl esters of the lipoproteins as well as in the plasma concentrations of the antioxidant vitamins A, C, and E. Lipid peroxidation was slightly increased prior to treatment. However, the C20/C16 ratio at 120 h was significantly decreased in comparison to the ratio at pretreatment (P<.025), at 6-8 h (P<.005), and at 24 h (P<.025). The C18/16 ratio at 120 h was also decreased in comparison to the ratio at 6-8 h (P<.025), indicating an increase in lipid peroxidation after correction of DKA. Vitamin A was below normal at pretreatment and was increased at 120 h (P<.05). Vitamin C was normal at pretreatment and decreased to low normal at 24 h (P<.005). Vitamin E was normal at pretreatment and decreased to below normal at 24 and 120 h, although the changes were not statistically significant. These data demonstrate that there is an increase in lipid peroxidation after the correction of DKA and therefore support the position that administering antioxidant vitamins during the treatment of DKA could be beneficial in minimizing oxidative stress and possibly both the acute and chronic complications of IDDM.
J Diabetes Complications
PMID:Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis. 1212 88

We investigated the pathophysiological significance in biomembranes of the redox dynamics of Vitamin E (alpha-tocopherol) which is lipophilic radical scavenger related to aging or pathologic status such as non-insulin-dependent diabetes mellitus or primary hyperlipidemia. Vitamin E eliminates lipid peroxyl radicals by the peroxidation chain reaction of the membrane lipid, and it becomes Vitamin E radical. Furthermore, the Vitamin E radical becomes Vitamin E quinone which is an oxidic metabolite of Vitamin E. Therefore, it was needed to determine the alpha-tocopherol and alpha-tocopherolquinone simultaneously to evaluate the antioxidative status of alpha-tocopherol in biomembranes exactly. For this purpose, we developed the assay method for the simultaneous determination of the two substances using HPLC system. Then we applied this method to basic and clinical research. 1) For the simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone, highly-sensitive measurement system by HPLC-multiple coulometric ECD was developed. This system is useful to estimate the redox dynamics of alpha-tocopherol in biomembranes. 2) The utilization rate of alpha-tocopherol in the erythrocyte membrane of 10- to 120-week-old rats was significantly increased, whereas alpha-tocopherol uptake in the erythrocyte membrane decreased age-dependently. Furthermore, a significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of the erythrocyte membrane were seen with age. 3) There was a strongly significant positive correlation between age and the utilization rate of alpha-tocopherol in the erythrocyte membrane of healthy volunteers aged between 23 and 103. 4) The alpha-tocopherol uptake in erythrocyte membrane was significantly lower in elderly non-insulin-dependent diabetes mellitus patients (average 68.1 years old) than in healthy subjects (average 71.8 years old). 5) The utilization rate of alpha-tocopherol in erythrocyte membrane and the alpha-tocopherol uptake in erythrocyte membrane were significant lower in elderly patients with primary hyperlipidemia (average 74.1 years old) compared to healthy subjects (average 71.2 years old). These findings suggest that the redox dynamics of alpha-tocopherol in biomembranes should be investigated with special regard to the onset, aggravation and complications of several diseases or aging as a result of oxidative stress. In addition redox dynamics were suggested to be useful to evaluate the grade of aging.
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PMID:[Relationship between aging and vitamin E]. 1240 40

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. Plasma LPO was influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasma LPO was the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.
Int J Exp Diabetes Res
PMID:Differential indicators of diabetes-induced oxidative stress in New Zealand White rabbits: role of dietary vitamin E supplementation. 1245 60

Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca(2+)-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca(2+)-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg x kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) x day(-1), orally) for 10 weeks. Ca(2+)-ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg x dl(-1)) in untreated-diabetic rats but decreased to 340+/-27 mg x dl(-1) in the vitamin E treated-diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca(2+)-ATPase activity was 0.483+/-0.008 U l(-1) in the control group and significantly increased to 0.754+/-0.010 U l(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca(2+)-ATPase activity (0.307+/-0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes.
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PMID:Effects of vitamin E on microsomal Ca(2+) -ATPase activity and calcium levels in streptozotocin-induced diabetic rat kidney. 1273 8

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes.
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PMID:Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats: protective role of vitamins C and E and selenium. 1290 28


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