Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spin-probe techniques has been used to study insulin-membranes interaction in erythrocytes by insulin dependent diabetes mellitus. The lipid peroxidation has been initiated by FeSO4-ascorbate. It was found the insulin defend the lipids in control by peroxidation, but no effect in insulin dependent diabetes mellitus erythrocytes. The mechanisms of the insulin-influence on the lipids peroxidation are discussed.
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PMID:[Effect of insulin on lipid peroxidation in the erythrocyte membranes of patients with insulin dependent diabetes mellitus]. 929 26

In diabetic nephropathy and hypertension, a major cause of mortality is from cardiovascular disease. Since low levels of antioxidants such as vitamin C have been associated with such complications, we have examined the uptake mechanisms for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM) patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive patients (HT) using mass assays of uptake and measuring AA using high-performance liquid chromatography. Precautions were taken to prevent oxidation of AA and to take into account the instability of DHA in buffers. DHA uptake was the major mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/- 2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1) h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON group (p < 0.001). There were no significant differences in the Km or passive membrane permeability for DHA or the AA uptake. DHA uptake showed a negative correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings suggest that impaired DHA uptake may be one component of the phenotype expressed by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially in the presence of hyperglycaemia, leads to impaired regeneration of AA and depletion of anti-oxidant defences, exposing such individuals to increased risk of cardiovascular disease.
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PMID:Uptake mechanisms for ascorbate and dehydroascorbate in lymphoblasts from diabetic nephropathy and hypertensive patients. 956 48

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20). We measured the total radical-trapping antioxidant parameter (TRAP), single antioxidants (sulfhydryl groups, uric acid, vitamin C, alpha-tocopherol, coenzyme Q10), malondialdehyde, oxidized low density lipoprotein (LDL) antibodies, lipid profile [cholesterol, triglyceride, lipoprotein (a)], homocysteine, and hemoglobin (Hb)A(1C). TRAP levels were elevated in the GSD Ia group (p <.01) and correlated with elevated uric acid levels (r = 0.72, p =.001). None of the other plasma antioxidants correlated with TRAP levels. DMI patients showed decreased sulfhydryl groups (p <.01) and a reduced ubiquinol-10 fraction (p <.01). Malondialdehyde (p <.001) and oxidized LDL autoantibodies (p <.05) were increased in the diabetic group. In FH patients, parameters of oxidative stress and TRAP did not differ from controls. We conclude that in GSD Ia an increased antioxidative defense in plasma may protect against lipid peroxidation and thus against premature atherosclerosis. Furthermore, we demonstrated that in DMI increased oxidative mechanisms are already present in childhood.
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PMID:Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia. 1208 88

Non Insulin Dependent Diabetes Mellitus is responsible for 60% cases of retinopathy in the population and is one of the common cause of blindness. Oxidative stress as measured by the levels of malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GPx) and vitamin C was measured in 50 normal controls, 40 diabetics without complications, 22 diabetics with proliferative and 20 with nonproliferative retinopathy respectively. Our finding suggests that lipid peroxidation increases (P < 0.001) with the increase in severity and duration of diabetes. Antioxidants SOD and vitamin C decrease with the progression of the disease, however GPx tends to increase in the later part of the disease.
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PMID:Lipid peroxidation and antioxidant status in patients with diabetic retinopathy. 1617 Sep 87

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

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.
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PMID:Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers. 1706 52

Familial aggregation has been shown for type 1 diabetes (T1D) although the nature of the factors (environment and/or genetics) responsible remains unclear. Familial clustering of diabetic nephropathy as well as of increased cardiovascular morbidity and early mortality has also been observed. This review describes the nearly 20 years history of our investigation in parallel with contemporary literature. The story is presented from the early years' strong focus on possible markers of T1D nephropathy (urinary albumin, urinary enzymes, erythrocyte Na/Li countertransport, and erythrocyte Na/H exchange) to the last clinical investigations to determine relevant biological markers of familial predisposition to T1D. Our studies of case-families recruited unaffected first-degree relatives of sporadic T1D cases and population-based controls. Unlike multiple-case families, these families are those less likely to carry a strong genetic predisposition. Participants were both interviewed and provided biological material for a detailed functional characterisation of their biochemical phenotype. These studies have initially excluded that the erythrocyte Na/H exchange could be a marker of diabetic nephropathy. On the contrary, NHE activity was significantly higher in T1D family members independently of the presence of renal disease. Basic science knowledge of NHE and its functional implications have also been reviewed. Unexpectedly, we found evidence of increased oxidative stress in nondiabetic normotensive relatives of T1D patients, apart from soluble markers of autoimmunity and despite seemingly intact antioxidant defences. Markers of oxidation were associated with markers of inflammation and we concluded that the familial increase in NHE activity could be ascribed to the direct stimulatory effect of oxidative stress. Relatives showed also immunological hallmarks and cardiovascular abnormalities that were related to indices of oxidative stress and metabolic syndrome. Other peculiarities emerged from measuring the erythrocytes redox system that exports electrons across the cell membrane to external oxidants as a function of cytoplasmic electron donor concentration. This electron transfer might reflect the functional state of membrane proton pumps that modulate intracellular redox levels. The transport system contributed to oxidation in T1D families, whereas in healthy people it protected from oxidation. Furthermore, dietary intake of vitamin C and sporting activities modulated erythrocyte electron transfer efficiency. The contribution of environmental factors was investigated using the European Prospective Investigation of Cancer and Nutrition questionnaires that provided evidence of common unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. However, lifestyle of T1D relatives was indistinguishable from those of controls, except for the higher daily intake of niacin and the lower physical activity levels. No difference in smoking or alcohol consumption emerged among families and controls. The oxidative stress is a non-specific though certain component of pathogenesis at numerous diseases states of aerobic organisms. Although molecular genetic analysis has produced significant progress in T1D phenotype, much remains to be learned about the molecular sequence of events leading from a generic familial pro-oxidant background to a sporadic form of T1D (where oxidative damage targets the insulin-secreting cells).
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PMID:Building a bridge between clinical and basic research: the phenotypic elements of familial predisposition to type 1 diabetes. 1734 47

The objective of this study was to examine the effect of maternal dietary intake during lactation on allergic sensitization at the age of 5 in children carrying HLA-DQB1-conferred susceptibility to type 1 diabetes. We analyzed data for 652 consecutively born children with complete information on maternal diet and allergen-specific immunoglobulin E (IgE) measurements who are participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition and allergy study. Analysis was performed using logistic regression. In models that included the significant uncorrelated dietary variables, maternal intake of butters and saturated fatty acids was associated with increased risk, while margarine was associated with a decreased risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarine and low-fat spreads were associated with decreased risk of sensitization to birch allergen. On the other hand, intake of potatoes decreased the risk, while vitamin C and eggs increased the risk, of cat allergic sensitization. Maternal intake of butters and saturated fatty acids during lactation may increase the risk, while margarines may decrease the risk, of sensitization to wheat allergen in the offspring. Maternal intake of potatoes, milks, and margarines may decrease the risk of sensitization to birch allergen. On the other hand, intake of potatoes may decrease the risk, while vitamin C and eggs may increase the risk, of cat allergic sensitization. These effects may persist regardless of maternal or parental allergic status.
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PMID:Maternal diet during lactation and allergic sensitization in the offspring at age of 5. 2122 76

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia-reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.
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PMID:Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. 2289 Dec 14

Vascular endothelial dysfunction, accelerated thickening of arterial intima, and changes in ventricular functions contribute to increased cardiovascular morbidity in type 1 diabetes mellitus (T1DM). This study aimed to investigate the functional-structural changes in the arteries and myocardium together with affection of highly sensitive C-reactive protein (hsCRP), circulating endothelial cells (CECs), and vitamin C levels in children with T1DM. Also, to test the association with early atherosclerotic changes. The study included 30 children with a diagnosis of T1DM and 30 healthy subjects matched by sex, age, and body mass index. Serum lipids, HbA1c, hsCRP, vitamin C, and CECs were detected. Corrected QT interval (QTc), cardiac dimensions, and left ventricular (LV) functions were assessed using conventional echocardiography. Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid intima-media thickness (IMT). The QTc interval was significantly higher in the diabetic patients than in the control subjects (P < 0.001). The findings showed LV diastolic dysfunction as reflected by significantly lower early peak flow velocity, decreased E/A ratio, increased early filling deceleration time (DcT), and prolonged isovolumic relaxation time (IVRT) (P < 0.001 for each). The children with diabetes had a significantly lower FMD response, increased IMT, lower vitamin C level, higher hsCRP, and higher CEC compared with the control subjects (P < 0.001 for each). A positive correlation between CEC and HbA1c was found (P = 0.004). An alteration in myocardial function and endothelial dysfunction may begin early with the association of early atherosclerotic changes. These changes are accelerated when glycemic control is poor. The authors recommend early and close observation of children with diabetes for any alterations in cardiac and vascular endothelial function. Vitamin C supplementation may reduce the risk of complications.
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PMID:Subclinical vascular endothelial dysfunctions and myocardial changes with type 1 diabetes mellitus in children and adolescents. 2459 24


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