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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of our study was to evaluate the effects of the administration of two dosages of vitamin C (Vit-C) (0.5 and 1g/day, vs. placebo) in elderly patients with type 2 diabetes mellitus on the intracellular levels of Vit-C and glutathione, and on the lipid peroxidation markers and vitamin E (Vit-E) content of low-density lipoprotein (LDL) and on LDL susceptibility to gamma radiolysis-induced peroxidation. Thirty-six patients were randomized into three groups. In patients on 0.5 g Vit-C/day versus the placebo group, a significant increase in cellular reduced glutathione level was observed (0.60+/-0.26 vs. 0.33+/-0.27). In patients on 1 g Vit-C/day versus placebo, a significant increase was also observed in cellular reduced glutathione (0.93+/-0.70 vs. 0.33+/-0.27), in Vit-C (5.66+/-2.00 vs. 2.72+/-1.88) and in vitamin E content of LDL (1.98+/-0.38 vs. 1.48+/-0.40). No change was observed in either group in basal levels of lipid peroxidation markers and in the susceptibility of LDL to peroxidation provoked by gamma-radiolysis. In conclusion, Vit-C has a dose-dependent effect on the cellular contents of antioxidants and on vitamin E content of LDL in elderly patients with type 2 DM. These changes are not sufficient to decrease the LDL susceptibility to peroxidation.
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PMID:Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes. 1807 12

Advanced glycation endproducts (AGEs) are unavoidable byproducts of various metabolic pathways. They are formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, and aging. In recent years, more compounds that prevent the formation of AGEs or degrade the existing AGEs have been produced and patented. They include: 1) aminoguanidine, 2) drugs used in the treatment of type 2 diabetes such as metformin and pioglitazone (patented), 3) angiotensin receptor blockers and angiotensin converting enzyme inhibitors, 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, 7) amino group capping agents such as aspirin, 8) enzymes that cause deglycation of Amadori products, the Amadoriases, 9) compounds that mostly break alpha-dicarbonyl cross-links such as phenacylthiazolium bromide and its stable derivative ALT-711 (Alagebrium), and 10) derivatives of aryl ureido and aryl carboxaminido phenoxy isobutyric acids (patented). While some of these anti-AGE compounds are being used in clinical practice (such as metformin, pioglitazone, pentoxyfylline and aspirin) or tested in clinical trials (such as aminoguanidine and ALT-711), most of them are commonly used as experimental tools to investigate the role of AGEs in different disease conditions.
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PMID:Methylglyoxal and advanced glycation endproducts: new therapeutic horizons? 1822 Nov 7

Diet and nutrition have substantial impact on reducing the incidence of diabetes mellitus, where oxidative stress is an important etiopathological factor. The combined protective role of low dose of naringin (15 mg kg(-1)) and vitamin C (25 mg kg(-1)) and high dose of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) on streptozotocin (STZ)-induced toxicity was studied in male Wistar rats. To induce type II diabetes mellitus, rats were injected with STZ intraperitoneally at a dose of 45 mg kg(-1) body weight. STZ-induced diabetic rats showed significant increase in blood glucose, water intake, food intake and glycated hemoglobin and significant decrease in plasma insulin, total hemoglobin, body weight and liver glycogen. Diabetic rats also showed significant decrease in the activity of hexokinase and significant increase in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in liver and kidney. The levels of plasma thiobarbituric acid reactive substances, lipid hydroperoxides and vitamin E were elevated while the level of reduced glutathione was decreased in diabetic rats. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid were increased in plasma, liver and kidney of diabetic rats. Oral administration of high doses of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) to diabetic rats for a period of 21 days normalized all the above-mentioned biochemical parameters. The effect exerted by naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) was similar to the effect exerted by insulin (6 units kg(-1)). Thus, our study shows the antihyperglycemic and antioxidant effects of naringin and vitamin C in STZ-induced type II diabetes mellitus in rats.
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PMID:Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. 1834 97

The hypotheses were: HISS-dependent insulin resistance (HDIR) accounts for insulin resistance that occurs with aging; HDIR is the initiating metabolic defect that leads progressively to type 2 diabetes and the metabolic syndrome; a synergistic antioxidant cocktail in chow confers protection against HDIR, subsequent symptoms of diabetes, and the metabolic syndrome. Male Sprague Dawley rats were tested at 9, 26, and 52 weeks to determine their dynamic response to insulin, the HISS (hepatic insulin sensitizing substance)-dependent component of insulin action, and the HISS-independent (direct) insulin action using a dynamic insulin sensitivity test. In young rats, the HISS component accounted for 52.3+/-2.1% of the response to a bolus of insulin (50mU/kg) which decreased to 29.8+/-3.4% at 6 months and 17.0+/-2.7% at 12 months. HISS action correlated negatively with whole body adiposity and all regional fat depots (r(2) = 0.67-0.87). The antioxidants (vitamin C, vitamin E, and S-adenosylmethionine) conferred protection of HISS action, fat mass at all sites, blood pressure, postprandial insulin and glucose. Data are consistent with the hypotheses. Early detection and therapy directed towards treatment of HDIR offers a novel therapeutic target.
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PMID:HISS-dependent insulin resistance (HDIR) in aged rats is associated with adiposity, progresses to syndrome X, and is attenuated by a unique antioxidant cocktail. 1853 70

Type 2 diabetes mellitus, the most prevalent and serious metabolic disease worldwide, is believed to result from the interaction between genetical and lifestyle factors. In genetically predisposed people, the combination of a hypercaloric ingestion and reduced physical activity is responsible for the appearance of insulin resistance. This state can be overcomed, until a certain point, with increments of insulin secretion (hyperinsulinemia). However, an insufficient compensation leads to a state of glucose intolerance, which can evolve to diabetes, according to actual knowledge. The noxious effects of the hyperglycemia, allied with the possible increase of free fatty acids, are mediated by highly reactive molecules, oxygen and nitrogen free radicals species (ROS and RNS). Recent data suggests that these reactive species are signalling molecules and are involved in the regulation of the cellular function, being its increased production or reduced elimination a cause of oxidative stress. Indeed, those free radicals act directly through oxidative damage on macromolecules (proteins, lipids, DNA) or indirectly, activating single transduction pathways sensible to stress mechanisms. In this review, we will consider the pathways recognized as the more significant in stress mechanisms, namely: NF-kB, JNK/SAPK, p38 MAPK, PKC, AGE/RAGE, hexosamines and poliol. These signalling cascades are believed to be responsible for the insulin resistance and reduced insulin secretion, therefore the use of innocuous antioxidant substances such as vitamin C, E and the a-lipoic acid, is seen as a possible step for type 2 diabetic complications management. We will also discuss acetylsalicylic acid potentialities in the above-mentioned pathologies.
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PMID:[Oxidative stress and its effects on insulin resistance and pancreatic beta-cells dysfunction: relationship with type 2 diabetes mellitus complications]. 1867 21

The apolipoprotein E (APOE) epsilon2 allele is reported to be associated with greater risk of renal impairment in type 2 diabetes. Relationships among APOE polymorphisms, renal impairment, and biochemical parameters were explored. A prospective study of 405 consenting Chinese type 2 diabetic patients [mean age +/- standard deviation (SD): 59.2 +/- 10.3 years] without advanced complications at entry was conducted. APOE genotyping and measurement of plasma biomarkers of oxidative stress and antioxidants were performed at entry. HbA1C, plasma glucose, lipids, creatinine, urine albumin/creatinine, and blood pressure were measured at entry and at up to 4 years of follow-up. APOE allelic frequencies were in Hardy-Weinberg equilibrium. Odds ratios of albuminuria at entry and/or during follow-up for different APOE groups were not significantly different. The non-epsilon2 (epsilon3/3, epsilon3/4, epsilon4/4) group had significantly greater plasma ascorbate (51.6 +/- 20.1 mumol/L) than the epsilon2 (epsilon2/2, epsilon2/3) group (44.5 +/- 16.2 mumol/L, P = 0.021), but higher plasma ascorbate levels did not seem to decrease the risk of renal impairment in the non-epsilon2 group. Baseline plasma lipid-standardized alpha-tocopherol levels were least in epsilon2 subjects with persistent albuminuria (3.6 +/- 1.1 mumol/mmol of total cholesterol plus triglycerides, P = 0.008) compared with epsilon2 subjects who had no albuminuria at entry or during follow-up (4.5 +/- 0.8 mumol/mmol of total cholesterol plus triglycerides). The APOE epsilon2 allele does not seem to be associated with increased risk of renal impairment in Chinese type 2 diabetic patients. Plasma lipid-standardized alpha-tocopherol may play a role in determining risk of renal dysfunction in type 2 diabetes.
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PMID:Type 2 diabetes mellitus and its renal complications in relation to apolipoprotein E gene polymorphism. 1877 43

Growing evidence indicates that insulin resistance and oxidative stress are involved in the pathogenesis of essential hypertension. In insulin-resistant states, like obesity and type 2 diabetes, altered glucose metabolism may lead to increased formation of methylglyoxal and other ketoaldehydes. Animal studies have shown that increased levels of endogenous aldehydes may lead to hypertension and oxidative stress. In animal models, the administration of vitamin C, vitamin B6 or alpha-lipoic acid reduced tissue levels of aldehydes, prevented oxidative stress, and lowered blood pressure. The purpose of this review article is to critically evaluate the available evidence for the role of dietary supplements in hypertension treatment.
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PMID:Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. 1885 66

The role of nutritional supplementation is of increasing interest with regard to ocular disease. Randomised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration, and formulations are now being developed for use by people with diabetes and diabetic retinopathy. The aim of this review was to synthesise the evidence for use of nutritional supplementation in type 2 diabetes. MEDLINE and EMBASE databases were searched using a systematic approach. Only double-masked randomised controlled trials were selected. A total of 50 trials were identified as suitable for inclusion. The potential role of alpha-lipoic acid, chromium, folic acid, isoflavones, magnesium, Pycnogenol, selenium, vitamin C, vitamin E, and zinc in the treatment of type 2 diabetes is discussed. The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors. Chromium was the most studied supplement, accounting for 16 of the 50 trials. A majority of the trials found a positive effect of chromium on fasting plasma glucose. Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures, but only when combined with soy proteins. Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1) or more.
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PMID:Nutritional supplementation for type 2 diabetes: a systematic review. 1907 53

Vitamin E has been studied extensively in the prevention of atherosclerosis. Cross-sectional population studies as well as randomized controlled intervention trials have demonstrated conflicting results. A recent meta-analysis of these trials has emphasized the ineffectiveness of vitamin E in atherosclerosis prevention, with a possibility of harm at higher dosages. However, vitamin E has several isomers, with the alpha form being available via dietary supplements and the gamma form being available via dietary foodstuffs. The gamma form of vitamin E demonstrates several superior properties (such as trapping reactive nitrogen species and detoxifying nitrogen dioxide) compared with alpha vitamin E. All clinical trials have used the alpha isomer, with little concern that this isomer of vitamin E may actually suppress the gamma isomer of vitamin E. We undertook a dose-response study in volunteers with type 2 diabetes mellitus to include all the dosages of alpha vitamin E that have been used in cardiovascular prevention trials to determine the effect of alpha vitamin E on gamma vitamin E. We also assessed the effect of alpha vitamin E on several traditional markers of atherosclerotic risk. We added vitamin C to the vitamin E because several clinical trials included this vitamin to enhance the antioxidant effects of alpha vitamin E. Volunteers received, in randomized order for a 2-week period, one of the following vitamin dosage arms: (1) no vitamins, (2) low-dose supplemental vitamins E plus C, (3) medium-dose supplemental vitamins E plus C, and (4) high-dose supplemental vitamins E plus C. Blood levels of both alpha and gamma vitamin E were measured as well as surrogate markers of oxidative stress, hypercoagulation, and inflammation during a high-fat atherogenic meal (to increase the ambient oxidative stress level during the study). The results demonstrate that alpha vitamin E levels increased in proportion to the dose administered. However, at every dose of alpha vitamin E, gamma vitamin E concentration was significantly suppressed. No beneficial changes in surrogate markers of atherosclerosis were observed, consistent with the negative results of prospective clinical trials using alpha vitamin E. Our results suggest that all prospective cardiovascular clinical trials that used vitamin E supplementation actually suppressed the beneficial antioxidant gamma isomer of vitamin E. No beneficial effects on several potential cardiovascular risk factors were observed, even when the vitamin E was supplemented with vitamin C. If a standardized preparation of gamma vitamin E (without the alpha isomer) becomes available, the effects of gamma vitamin E on atherosclerotic risk will warrant additional studies.
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PMID:The response of gamma vitamin E to varying dosages of alpha vitamin E plus vitamin C. 1930 66

Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.
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PMID:Antioxidants prevent health-promoting effects of physical exercise in humans. 1943


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