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

Oxygen free radicals produced during normal aerobic metabolism have been implicated in several pathophysiological mammalian processes. The importance of free radical-mediated fatty acid oxidation has received much attention. The generation of active oxygen species may lead to lipid peroxidation and formation of reactive products, which may be involved in severe damage of cell molecules and structures. Free radical metabolism in pregnancy and in diabetes mellitus is still unclear. To add new insights to the question, changes in lipid peroxidation products and activities of three antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) in maternal red blood cells haemolysates were evaluated in pregnant women with insulin-dependent diabetes mellitus (IDDM-PW) and in healthy pregnant women (HPW). Healthy non-pregnant women were the control group for IDDM-PW and HPW, respectively. Pregnancy provoked an increase of lipoperoxidation products and an high SOD activity since early pregnancy, while CAT and GPX activities did not change during gestation. IDDM-PW showed higher content of lipoperoxidation breakdown products and lower SOD activity at each trimester, if compared with HPW; moreover, a slight increase of CAT and SOD activity is reported during late diabetic pregnancy. IDDM-PW were in very good metabolic control at time of sampling. The variations reported suggest an easier membrane lipoperoxidability and, consequently, an easier membrane damage during diabetic gestation.
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PMID:Lipid peroxidation products and antioxidant enzymes in red blood cells during normal and diabetic pregnancy. 811 55

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

In our present work we attempt to clarify the pro-, antioxidant status (redox status) of blood and the red blood cell (RBC) filtration changes in type 1 (insulin dependent diabetes mellitus = IDDM) diabetic patients, broadening our biochemical knowledge about the mechanism of disease. Further on we try to apply our observations in therapy. Our studies on enzymes and the pro- and antioxidant status in type 1 diabetes are closely related to earlier works. Our studies on antioxidants have been extended deeper on redox conditions for example on the reduced and oxidized glutathione (GSH and GSSG) and glutathione reductase activity. The properties and changes of antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) as well as lipid peroxidation (LP) have been studied earlier without selecting the different type of human diabetics. At the same time the red blood cell filtration characteristics are compared also with normal values. The results of our studies confirmed the earlier findings that human diabetes is accompanied by a strong oxidative predominance (oxidative stress) in blood.
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PMID:Pro-, antioxidant and filtration changes in the blood of type 1 diabetic patients. 970 3

This study showed that citiolone (CIT), a free radical scavenger, significantly increased superoxide dismutase (P < 0.001 vs. untreated NOD, NMMA-treated, and silica-treated animals), catalase (P < 0.01 vs. untreated NOD), and glutathione peroxidase (P < 0.001 vs. untreated NOD and C57BL6/J) values. Silica treatment was capable of counteracting the plasma antioxidant capacity (TRAP) decrease observed in untreated NOD mice, although it did not block the blood glucose rise and insulitis progression in type 1 diabetes significantly. Conversely, early silica administration was able to deplete macrophages (as demonstrated by immunocytochemistry) and to block the rise in blood glucose levels and insulitis progression significantly. Silica-treated animals in this study showed the highest TRAP levels, demonstrating that depletion of macrophages also was able to improve the antioxidant status. This study suggested that macrophages are essential for type 1 diabetes development and showed that they also are involved when the antioxidant status is affected. The reported findings are significant in view of previous studies indicating that oxygen and/or nitrogen free radicals contribute to the islet beta-cell destruction in type 1 diabetes animal models.
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PMID:Macrophages and antioxidant status in the NOD mouse pancreas. 982 94

To evaluate oxidative stress in type I diabetes mellitus, two antioxidant enzymes in erythrocytes, copper-zinc superoxide dismutase (SOD EC 1.15.1.1.) and seleno-dependent glutathione peroxidase (GSH-Px; EC 1.11.19), and two indexes of peroxidation in plasma, thiobarbituric acid reactive substances (TBARS) and organic hydroperoxides (OHP), were measured in 118 patients with insulin-dependent diabetes mellitus (IDDM), classified in accordance with the presence or absence of vascular complications and the degree of metabolic control established by the HbA1c level. Ninety healthy subjects made up the control group. According to our results, plasmatic TBARS and OHP concentrations are significantly higher in diabetics than in controls, and these differences are accentuated in diabetic people with vascular disorders. The GSH-Px activity was significantly reduced in diabetic patients with poor and medium metabolic control in relation to the control group, regardless of the existence or absence of vascular disorders. No differences in SOD activity between diabetic and control groups were found. A significant positive correlation between TBARS and HPO (r=0.683, p<0.001) was found in both the control and diabetic groups. Among the lipid parameters studied, there were only significantly positive correlations between TBARS and total cholesterol; TBARS and triglycerides; OHP and total cholesterol and OHP and triglycerides. Positive correlations between TBARS and HbA1c and between OHP and and HbA1c, and negative correlations between GSH-Px and HbA1c and between SOD and HbA1c were also found. The multiple regression analysis shows that TBARS and HPO correlate negatively with GSH-Px. There was no significant correlation with SOD.
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PMID:Lipid peroxidation and antioxidant enzyme activities in patients with type 1 diabetes mellitus. 1035 23

Pancreatic beta cells are sensitive to reactive oxygen species and this may play an important role in type 1 diabetes and during transplantation. Beta cells contain low levels of enzyme systems that protect against reactive oxygen species. The weakest link in their protection system is a deficiency in the ability to detoxify hydrogen peroxide by the enzymes glutathione peroxidase and catalase. We hypothesize that the deficit in the ability to dispose of reactive oxygen species is responsible for the unusual sensitivity of beta cells and that increasing protection will result in more resistant beta cells. To test these hypotheses we have produced transgenic mice with increased beta cell levels of catalase. Seven lines of catalase transgenic mice were produced using the insulin promoter to direct pancreatic beta cell specific expression. Catalase activity in islets from these mice was increased by as much as 50-fold. Northern blot analysis of several tissues indicated that overexpression was specific to the pancreatic islet. Catalase overexpression had no detrimental effects on islet function. To test whether increased catalase activity could protect the transgenic islets we exposed them to hydrogen peroxide, streptozocin, and interleukin-1beta. Fifty-fold overexpression of catalase produced marked protection of islet insulin secretion against hydrogen peroxide and significantly reduced the diabetogenic effect of streptozocin in vivo. However, catalase overexpression did not provide protection against interleukin-1beta toxicity and did not alter the effects of syngeneic and allogenic transplantation on islet insulin content. Our results indicate that in the pancreatic beta cell overexpression of catalase is protective against some beta cell toxins and is compatible with normal function.
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PMID:Overexpression of catalase provides partial protection to transgenic mouse beta cells. 1051 87

Oxidative stress plays a major role in the development of chronic complications of diabetes. The aim of our study was to evaluate the selected components of the antioxidative system in well metabolically controlled diabetic patients. We also decided to assess the correlation between these parameters and duration of disease and the presence of it's late complications. The study was entered by 30 patients with type 1 diabetes (18 female and 12 male, aged 30.2 + 10.8 years with mean duration of disease 8.37 + 6.56 years, HbA1c 6.8 + 1.6%). 24 healthy, sex- and age-matched volunteers served as controls. We assessed the following parameters: reduced glutathione in erythrocyte lysate (colorimetric method by Bioxytech GSH-400), serum glutathione peroxidase (enzymatic immunological method by Bioxytech pl. GPx-EIA) and plasma superoxide dismutase activity (colorimetric method based on cytochrome c reduction). In comparison with controls, we found significantly higher reduced glutathione level (11.20 + 0.79 vs 3.92 + 0.62 mumol/l, p < 0.001) and markedly lower dismutase activity (27.49 + 1.32 vs 39.73 + 4.45 U/ml, p < 0.001). The levels of glutathione peroxidase did not differ significantly from values obtained in healthy subjects. We did not observe any correlation between the analysed parameters and duration of diabetes, HbA1c or presence of chronic complications of disease. The obtained results might indicate that antioxidative systems in the state of good metabolic control of diabetes have adaptive properties.
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PMID:[Evaluation of selected components in antioxidant systems of blood in patients with diabetes]. 1139 14

Oxidative stress (OS) plays an important role in the pathogenesis of Type 1 diabetes mellitus (DM). The aim of the study was to compare OS parameters in diabetic children and their first-degree relatives. Fifty diabetic children from the West Bohemian Region were examined as well as their 32 siblings (12 Boys and 20 girls) and 65 of their parents during a period of 6 months. Thirty healthy sex- and age-matched children studied before planned surgeries were normal controls for children, 40 healthy adult volunteers were controls for parents. OS parameters were evaluated in all participants of the study (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; plasma antioxidant capacity, AOC; reduced glutathione, GSH; and malondialdehyde, MDA) and also Type 1 DM-associated antibodies (ICA and GADA). The results in diabetic children showed significantly lower GSHPx and AOC and increased MDA when compared with healthy children. Similar findings were found in their siblings but without statistical significance. It is consequently evident that decreased antioxidative protection and simultaneous free radical (FR) overproduction occur in diabetic children and that there is a similar, but not significant, tendency in their siblings. The findings warrant reducing OS in diabetic children and postponing disease onset in susceptible relatives.
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PMID:Parameters of oxidative stress in children with Type 1 diabetes mellitus and their relatives. 1250 49

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.
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PMID:Circulating biomarkers of oxidative stress in complicated pregnancies. 1259 16

Increased flux of glucose through the polyol pathway may cause generation of excess reactive oxygen species (ROS), leading to tissue damage. Abnormalities in expression of enzymes that protect against oxidant damage may accentuate the oxidative injury. The expression of catalase (CAT), CuZn superoxide-dismutase (CuZnSOD), glutathione peroxidase (GPX), and Mn superoxide-dismutase (MnSOD) mRNA was quantified in peripheral blood mononuclear cells-obtained from 26 patients with type 1 diabetes and nephropathy, 15 with no microvascular complications after 20 years' duration of diabetes, and 10 normal healthy control subjects-that were exposed in vitro to hyperglycemia (HG) (31 mmol/l D-glucose). Under HG, there was a twofold increase in the expression of CAT, CuZnSOD, and GPX mRNA in the patients without complications and the control subjects versus patients with nephropathy (P < 0.0001), and MnSOD did not change in any of the groups. The aldose reductase inhibitor zopolrestat partially restored the levels of CAT, CuZnSOD, and GPX mRNA in the patients with nephropathy (P < 0.05). There was a highly significant correlation between increased aldose reductase (ALR2) expression, CAT, CuZnSOD, and GPX mRNA levels under HG conditions and polymorphisms of ALR2 in the patients with nephropathy (P < 0.00001). In conclusion, these results suggest that high glucose flux through aldose reductase inhibits the expression of antioxidant enzymes.
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PMID:The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy. 1260 29


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