Polymorphism of catalase gene promoter in Romanian patients with diabetic kidney disease and type 1 diabetes.

Hyperglycaemia leads to ROS (Reactive oxygen species) generation, affecting the cells that cannot decrease glucose uptake such as: glomerular epithelial cells, mesangial cells and proximal tubule cells. ROS excess seems to activate important pathogenic pathways of development of diabetic nephropathy. The decrease of CAT activity, one of the most important antioxidant enzymes, following to some genetic defects, may be a risk factor for diabetic nephropathy. The purpose of this study is to investigate the association of 21A/T (rs7943316) polymorphism of CAT gene with advanced diabetic nephropathy in patients with type 1 diabetes in Romania. There have been studied 238 patients with T1D (type 1 diabetes), divided into the group with diabetic nephropathy (DN) (106 patients) and the group without renal affectation (132 patients). The genotyping has been made by using PCR-RFLP technique. The analysis of association has been made by using DeFinetti programme. The value considered significant has been p < 0.05. There has been a deviation from Hardy-Weinberg equilibrium in the group with diabetic nephropathy (p = 0.019), the equilibrium being preserved by the control group (p = 0.771). T allele does not confer a risk for advanced diabetic nephropathy (ORT = 0.757, 95% C.I. = 0.405-1.414; P = 0.381), the result being statistically insignificant even taking into consideration the risk allele A (ORA = 0.793, 95% C.I. = 0.465-1.350; P = 0.392). The results remain concordant too after applying the Cochran -Armitage test. Our data do not suggest an effect of 21A/T (rs7943316) polymorphism in the susceptibility for diabetic nephropathy in Romanian patients with type 1 diabetes. Further studies are necessary in order to demonstrate or exclude the role of CAT gene in diabetic nephropathy in patients with type 1 diabetes.

The effect of magnesium deficit on serum immunoglobulin concentrations in type 1 diabetes mellitus.

The aim of this study was to evaluate the correlation between changes in the concentration of serum magnesium and serum immunoglobulin concentrations in type 1 diabetes mellitus. In this study were included 110 patients with type 1 diabetes mellitus (64 men and 46 women) with ages ranging from 19 to 54 years (mean age 41.6+/-6.8 years). The mean duration of the disease was 8.7+/-7.5 years. Thirty-six healthy subjects served as a control group. The serum magnesium concentrations were evaluated by VITROS 750 XRC, Johnson & Johnson kit, (Ortho Clinical Diagnostics). Total serum IgA, IgG and IgM were determined by laser nephelometry (MININEPH The Binding Site kit). Values are means (x) + standard deviations (SD). Serum magnesium concentrations confirmed the magnesium deficit in patients with type 1 diabetes mellitus (1.8+/-0.11 mg/dL, range 1.73-2.47 mg/dL vs 2.2+/-0.2 mg/dL, range 1.6-2.4 mg/dL). In patients with type 1 diabetes mellitus, IgA levels are mildly elevated (4.03+/-0.51 g/L vs 3.43+/-0.48 g/L; p<0.05), while IgG levels are decreased (7.38+/-0.76 g/L vs 9.92+/-1.32 g/L; p<0.001) and IgM levels are almost constantly normal (1.18+/-0.16 g/L vs 1.22+/-0.15 g/L; p>0.05). Therefore, magnesium deficit has profound immunosuppressive capabilities in patients with type 1 diabetes mellitus by significantly reducing the number of IgG synthesizing cells and serum IgG concentrations.

Glimepiride-induced prevention of diabetes and autoimmune events in the BB rat: revised.

The purpose of this study was to determine whether Glimepiride, an oral sulfonylurea drug, prevents the onset of diabetes in diabetic prone BB rats. S750181, a sulfonylurea drug that has minimal in vivo glucose metabolic effects, was also tested. In addition, the shortest period of sulfonylurea treatment required for prevention was determined. Eighty rats were studied for all treatment periods with 40 receiving a daily oral gavage dosage of glimepiride and 40 receiving a daily oral gavage dosage of vehicle solution. Diabetes onset was monitored by glycosuria and blood glucose levels. In study I, with a treatment period of 35-142 days of age, Glimepiride-treated rats showed a 32% incidence of diabetes, whereas control rats had a diabetes incidence of 55% (p < 0.04). In study II, with a treatment period of 60-140 days of age, Glimepiride-treated rats showed a 29% incidence of diabetes compared to 54% in controls (p < 0.03). Further, comparing the time of diabetes onset between the Glimepiride and control groups showed that Glimepiride delays diabetes onset (p < 0.02). In study III, with a treatment period of 60-100 days of age, Glimepiride-treated rats showed a 17% overall diabetes incidence at 170 days, whereas the controls were 43% (p < 0.01). In study IV, with a treatment period of 60-140 days of age, S750181-treated rats showed a 38% diabetes incidence and the control group showed a 43% diabetes incidence. There was no significant delaying or prevention effect observed in the S750181 group. To determine if Glimepiride affected autoimmune events, the severity of islet inflammation was examined. In study I, islet histology from total and nondiabetic animals indicated that Glimepiride-treated rats had a lower severity of islet inflammation than that of the control rats (p = 0.023). These studies show that a) Glimepiride has diabetes preventive effects, b) shorter treatment periods of only 40 days can be effective and c) Glimepiride decreases the severity of islet inflammation.