thiobarbituric-acid and Diabetes-Mellitus--Type-2

Lipid peroxides and fluorescent serum proteins, possible markers of free radical activity, are increased in diabetic patients, particularly those with angiopathy. Captopril, an angiotensin converting enzyme (ACE) inhibitor, scavenges free radicals in vitro independently of ACE inhibition. This is probably due to the presence of a sulphydryl group which is not present in other ACE inhibitor drugs. We have compared the effects of captopril and enalapril on free radical activity in thirty-two diabetic subjects with hypertension (BP greater than 160/95 mmHg). After a three week run-in period on no antihypertensive therapy, patients were randomly allocated to receive captopril or enalapril, the dose titrated according to BP response. After three months, BP was well controlled in both groups and glycaemic control unchanged. Both drugs were associated with a reduction of fluorescent IgG (captopril:Baseline [BL] 0.564 vs. 12 weeks [w] 0.428, P less than 0.05, enalapril:BL 0.603 vs. 12w 0.422 P less than 0.05) and thiobarbituric acid reactive material (captopril:BL 2.35 nmol MDA vs. 12w 1.46 nmol, P less than 0.05, enalapril:BL 2.44 nmol vs. 12w 1.72 nmol, P less than 0.01). In contrast to in vitro studies, there was no significant difference between the drugs when used in therapeutic doses, questioning a hypothesised advantage of captopril over enalapril.

Topics: Adult; Aged; Blood Proteins; Captopril; Diabetes Mellitus, Type 2; Enalapril; Female; Free Radical Scavengers; Free Radicals; Humans; Hypertension; Lipid Peroxides; Male; Middle Aged; Thiobarbiturates

Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a-wave, b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.

Topics: Animals; Catalase; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Electroretinography; Glucose; Immunohistochemistry; Male; Melatonin; Rats; Rats, Wistar; Thiobarbiturates; Tumor Necrosis Factor-alpha

Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with increased lipid peroxidation (oxidative stress). This may contribute to the accelerated vascular disease associated with these conditions. It is not known whether the coexistence of elevated homocysteine levels will stimulate oxidative stress further than that caused by diabetes alone.. Plasma concentrations of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, were measured in patients with NIDDM who had previously had a methionine load test; some of the patients had hyperhomocysteinemia.. Plasma TBARS concentrations were elevated in diabetics with vascular disease. The additional presence of hyperhomocysteinemia was not associated with a further increase in plasma TBARS concentrations.. Lipid peroxidation is increased in patients with diabetes mellitus and macrovascular disease and is not further elevated by the coexistence of elevated homocysteine levels. It is possible that diabetes maximally stimulates oxidative stress and any further acceleration of vascular disease in patients who have coexistent hyperhomocysteinemia is mediated through mechanisms other than lipid peroxidation.

Topics: Adult; Analysis of Variance; Brain Ischemia; Carotid Artery Diseases; Case-Control Studies; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Free Radicals; Homocysteine; Humans; Hypoglycemic Agents; Insulin; Lipid Peroxidation; Male; Methionine; Middle Aged; Oxidative Stress; Peripheral Vascular Diseases; Sulfonylurea Compounds; Thiobarbiturates

Increased levels of lipid peroxides have been implicated in the pathogenesis of diabetic complications. A convenient and sensitive method for estimation of lipid peroxide concentration is the quantitative estimation of their metabolic end-product malonyldialdehyde (MDA) expressed in mumol/L using the thiobarbituric acid test. The mean fasting MDA value in the plasma of 26 Arab subjects with NIDDM was significantly higher than in healthy controls (14.3 +/- 8.3 vs 2.3 +/- 3.4, p less than 0.001). Within a group of nine diabetic patients with markedly elevated MDA values (greater than 20 mumol/L), eight subjects had retinal changes, four had evidence of coronary artery disease and three had manifest cerebrovascular disease. Macroproteinuria was documented in only three patients in this same group. The mean body mass index was 28.7 +/- 5.4 and the glycaemic control was unsatisfactory with a mean glycosylated hemoglobin of 10.1 +/- 1.5%. The MDA results in an Arabic population were similar to reports in Japanese and British patients and should prove useful as a laboratory test in assessing the severity of the diabetic state, as well as a complementary test in diagnosis and management.

Topics: Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Indicators and Reagents; Kuwait; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Reference Values; Regression Analysis; Thiobarbiturates