Higher blood pressure in normoalbuminuric type 1 diabetic patients with a familial history of type 2 diabetes

Background: To adress whether type 1 diabetic patients with type 2 diabetic first degree relatives are different from others in terms of cardiovascular risk factors, insulin resistance and daily insulin dosage

Effect of oxidative stress on glutathione pathway in red blood cells from patients with insulin-dependent diabetes mellitus

Recently, increased oxidative stress and impaired antioxidant defense have been suggested as a contributory factor for initiation and progression of complications in diabetes. Although glutathione (GSH) and the enzymes included by glutathione redox cycle have an important role for protection of cells against free radical-mediated damage, they may be susceptible to oxidation themselves. We examined the susceptibility of the GSH pathway to oxidation and inactivation in subjects with well-controlled and poorly controlled insulin-dependent diabetes mellitus (IDDM) versus controls and the effect of glycemic control on this susceptibility. Red blood cells (RBCs) were isolated, RBC level of GSH, activity of glutathione peroxidase (G-Px), and glutathione reductase (G-Red) were measured at the baseline and after a 2-hour incubation with hydrogen peroxide. Significant decreases were observed in the GSH level and in the activity of GSH peroxidase and GSH reductase in all the groups after the incubation with hydrogen peroxide. Maximum decrease was observed in the poorly controlled diabetic group for all parameters. This result indicates that the GSH pathway is susceptible to oxidation; and this susceptibility increases in poorly controlled diabetics. Therefore, insufficient antioxidant defense by the GSH pathway may be one of the factors responsible for development of complications in patients with IDDM. Copyright 2002, Elsevier Science (USA). All rights reserved

Susceptibility of glutatione and glutathione-related antioxidant activity to hydrogen peroxide in patients with type 2 diabetes: effect of glycemic control

Objectives: The aim of the present study was to examine the susceptibility of glutathione (GSH) and glutathione related antioxidant enzymes to oxidation in type 2 diabetic patients with and without glycemic control

O-6-methylguanine DNA methyltransferase activity in diabetic patients

In the present study, we evaluated O-6-methylguanine-DNA methyltransferase (MGMT) activity in diabetic patients. The study was performed on 27 patients with Type 1 diabetes, and 42 with Type 2 diabetes. Patients with complications were excluded from the study. 36 non-diabetic volunteers, non-smokers who do not consume alcoholic beverage, were chosen from the medical staff as control subjects. MGMT activity was measured by the transfer of radiolabeled methyl groups from a prepared methylguanine-DNA substrate to the enzyme fraction of leukocyte extract. Leukocyte MGMT activity was significantly reduced in both Type 1 and Type 2 diabetes patients as compared with control subjects (P < 0.001). The present study demonstrates decreased MGMT activity in leukocytes from patients with Type 1 and Type 2 diabetes. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved

Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes

The first aim of the present study was to examine the relationship between reduced glutathione (GSH) level, a powerful cellular antioxidant, and oxidative damage to DNA; and secondly, to see the effect of glycemic control on oxidative DNA damage in type 2 diabetics. We determined GSH level and, using the comet assay, formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites which indicates oxidised guanine in freshly isolated blood from age-matched type 2 diabetics and controls. We found significant differences between men and women in the control group for both GSH and Fpg-sensitive sites. Therefore, we compared the controls and type 2 diabetics separately in men and women. GSH level of whole blood was found to be lower, Fpg-sensitive sites in leukocytes was found to be higher in the both type 2 diabetic men and women, as compared with their respective controls. When the diabetic group was divided into two groups as well-controlled diabetics and poorly-controlled diabetics with respect to glycosylated haemoglobine levels, it was found that Fpg-sensitive sites was significantly higher in the poorly-controlled diabetics than in the well-controlled diabetics in both the men and women. GSH level was lower in the poorly-controlled diabetics but not significantly. Fpg-sensitive sites were found to be moderately correlated with both glycosylated haemoglobine and GSH, and weakly correlated with glucose. Data indicate that decreased GSH level may be a contributory factor for enhanced oxidative DNA damage in type 2 diabetics; and chronic hyperglycemia derived from poorly-controlled diabetic conditions may induce oxidative DNA damage in these patients. (C) 2002 Elsevier Science B.V. All rights reserved

Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment

OBJECTIVE - Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in beta-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease

DNA damage and antioxidant defense in peripheral leukocytes of patients with type I diabetes mellitus

We determined relationship among DNA damage, nitric oxide (NO) and antioxidant defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G-Px) activity of the leukocytes were measured by spectrophotometric kits. Serum glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients, as expected. Differences in measured parameters between controls and patients were assessed in men and women separately. There was no significant difference between patient and control groups in neither men nor women for nitrite level. Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px activities of the leukocytes were found to be decreased in both men and women of patient group as compared to their respective controls. Significant correlations were determined between strand breakage and HbA(1c) (r 0.37, P < 0.05); Fpg-sensitive sites and HbA(1c) (r = 0.59, P < 0.01); Fpg-sensitive sites and glucose (r = 0.45, P < 0.02); Fpg-sensitive sites and SOD (r = -0.48, P < 0.02); HbA(1c), and SOD (r = -0.50, P < 0.02). In conclusion, impaired antioxidant defense in leukocytes of patients with Type I DM may be one of the responsible mechanisms for increased DNA damage in those patients. (C) 2003 Elsevier Science B.V. All rights reserved