Oxidative stress, diabetic patients

Diabetic nephropathy consequently results in chronic renal insufficiency and need for dialysis. End-stage renal failure is accompanied by increased oxidative stress and patients are at increased risk to develop cardiovascular disease. Oxidatively modified LDL was shown to be localized in kidneys (Exner et al. 1996) and a role for OxPL in kidney disease was suggested. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Collier et al. (1990) extended their studies relating to oxidative stress and diabetes by demonstrating that the levels of several free-radical scavengers (red cell superoxide dismutase, plasma thiols) were significantly reduced in 22 type 2 diabetic patients (mean age 53 years) in comparison with 15 control subjects (mean age 51 years). No significant diflFerences in red cell lysate thiols or... 

In a recent study, serum ascorbate concentrations were significantly reduced in a group of elderly diabetic patients (w = 40, mean age 69 years) in comparison with an age-matched group of non-diabetic controls ( = 22, mean age 71 years), and this reduction was more pronounced in those patients with microangiopathy (Sinclair et al., 1991). Diabetic patients were shown to have a high serum dehydroascorbate/ascorbate ratio indicative of increased oxidative stress. Ascorbate deficiency was partially corrected by vitamin C supplementation, 1 g daily by mouth, but the obvious disturbance in ascorbate metabolism in the diabetic patients was accentuated, since serum ascorbate concentrations fell (after the initial rise) despite continued vitamin C supplementation (Fig. 12.3). 

Hydroxy-10,12-octadecadienoic acid, which is formed by the reduction of 9-HPODE, was identified in the erythrocyte membrane phospholipid of diabetic patients [83]. It was suggested that this compound was formed as a result of glucose-induced oxidative stress in the reaction of hydroxyl radicals with linoleic acid. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

Ghiselli A, Laurenti O.deMattiaG, Maiani G, Ferro-Luzzi A (1992) Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients. Free Rad Biol Med 13 621-626... 

C20. Ceriello, A., Bortolotti, N., Motz,E., Lizzio, S., Catone, B., Assaloni, R., Tonutti, L., andTaboga, C., Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation A pleasant approach to the prevention of cardiovascular disease in diabetes. Eur. J. Clin. Invest. 31, 322-328 (2001). 

M8. Marra, G., Cotroneo, P., Pitocco, D., Manto, A., Di Leo, M. A., Ruotolo, V., Caputo, S., Giardina, B., Ghirlanda, G., and Santini, S. A., Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes A case for gender difference. Diabetes Care 25, 370-375 (2002). 

Monnier, L., E. Mas, C. Ginet, F. Michel, L. Villon, J.P. Cristol, and C. Colette. 2006. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295 1681-1687. 

Mortality secondary to cardiovascular disease is 10 to 30 times greater in dialysis patients than in the general population. In addition to traditional cardiac risk factors such as diabetes, hypertension, hyperlipidemia, tobacco use, and physical inactivity, patients with kidney disease have other unique risk factors. Among these are hyper-homocysteinemia, elevated levels of C-reactive protein, increased oxidant stress, and hemodynamic overload. Complications previously discussed such as anemia and metabolic disorders of CKD are also contributory. In particular, arterial vascular disease (i.e., atherosclerosis) and cardiomyopathy are the primary types of cardiovascular disorders present in the CKD population. These disorders lead to development of ischemic heart disease and its manifestations including myocardial infarction. As a predominant comorbidity, cardiovascular disorders and their sequela are the leading cause of death in the ESKD population. ... 

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