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Effect of gliclazide on thromboxane B2, parameters of haemostasis, fluorescent IgG and lipid peroxides in non-insulin dependent diabetes mellitus.

Abnormalities of platelet aggregation, and increased levels of lipid peroxides and denatured proteins have been implicated in the pathogenesis of diabetic microangiopathy. Seventeen non-insulin dependent diabetics (mean age 65.7) on established sulphonylurea therapy were converted to an equivalent dose of gliclazide. They were studied at baseline and intervals to 36 weeks. Thromboxane B2 (TXB2) and beta thromboglobulin (beta TG) were measured by radioimmunoassay. Lipid peroxides were measured as total diene conjugates (DC) by scanning UV spectrophotometry and thiobarbituric acid reactivity (TBA) by absorbance at 532 nm. Oxidation products of proteins were represented by fluorescence/UV ratio of immunoglobulin G (*IgG) separated from serum by HPLC. Glycaemic control remained stable throughout the study. TXB2 fell from 734 +/- 233 ng/l at 0 weeks to 488 +/- 155 at 36 weeks, p less than 0.001 and beta TG from 120 +/- 70 ng/ml to 48 +/- 18 at 24 weeks, p less than 0.005. Lipid peroxides fell between 0 and 36 weeks; DC from 0.71 +/- 0.28 to 0.32 +/- 0.09, p less than 0.001 and TBA from 29.6 +/- 22.4 to 4.0 +/- 2.2, p less than 0.001. Fluorescent IgG ratio fell from 1.44 +/- 0.36 to 0.32 +/- 0.07, p less than 0.001. This data provides evidence for a specific action of gliclazide on thromboxane synthesis and platelet aggregation. This is independent of glycaemic control and may in part be mediated by the observed fall in lipid peroxides.

Aged↗

Vitamin C metabolites and microangiopathy in diabetes mellitus.

Recent evidence has suggested that diabetic microangiopathy is associated with increased free radical induced oxidative damage. Ascorbic acid (AA) is a free radical scavenger and using a specific HPLC method we have investigated its concentration and that of its oxidized metabolite dehydroascorbic acid (DHAA) in diabetic patients and matched normal controls. The findings have been related to the presence of microangiopathy and to glycaemic control. Ascorbic acid levels were significantly lower in diabetics (mean +/- SD 42.5 +/- 26.2 mumol/l) compared with controls (58 +/- 21 mumol/l p less than 0.02). Although there was no differences in DHAA levels between the groups the ratio DHAA/AA was increased in diabetics (0.72 +/- 0.8) compared with controls (0.4 +/- 0.2 p less than 0.05). There were no significant differences between insulin and non-insulin dependent patients in these measurements and there was no association with the presence of microangiopathy or poor glycaemic control. The plasma ratio DHAA/AA may be a reflection of increased oxidative stress and our results suggest that diabetics may be less able to prevent oxidative damage occurring due to their lower AA concentrations.

Ascorbic Acid↗

Human diabetic cataract: role of lipid peroxidation.

To test whether impaired glutathione redox status may be related to lens oxidative damage in humans, we measured glutathione (total and oxidised forms) and malondialdehyde, a lipid peroxidation product, in clear lenses and diabetic and non-diabetic cataracts. Diabetic cataracts were divided into 2 subgroups with either intact or abnormal haemo-ocular barrier as evaluated by preoperative iridography. Decreased total glutathione values were observed in cataractous (diabetic and non-diabetic) as compared to clear lenses (p < 0.001), whereas enhanced oxidised glutathione levels were found in diabetic caracts as compared to non-diabetic ones and clear lenses (p < 0.001). Malondialdehyde concentrations were significantly higher in all types of cataracts, especially myopic and diabetic ones, than in clear lenses (p < 0.001). Moreover, malondialdehyde levels in diabetic lenses were inversely correlated with total glutathione (r = 0.80; p < 0.001) and linearly correlated with oxidised glutathione values (r = 0.76; p < 0.001). Finally, glutathione redox status was found to be more seriously impaired in lenses from diabetic patients with abnormal than intact haemo-ocular barrier. These data suggest a contributory role of lipid peroxidation and glutathione oxidation and consumption in the pathogenesis of cataract, especially in diabetic lenses with haemo-ocular barrier abnormality.

Aged↗

UK Prospective Diabetes Study (UKPDS). XI: Biochemical risk factors in type 2 diabetic patients at diagnosis compared with age-matched normal subjects.

A total of 507, newly diagnosed, white Caucasian Type 2 diabetic patients entered into UK Prospective Diabetes Study, mean age 52 +/- 9 (SD) years have been compared with 195 age-matched normal subjects (fasting plasma glucose < 6 mmol l-1) who had no known first degree relatives with diabetes. Diabetic patients were more obese BMI(kg m-2) 30.1 +/- 6.2 vs 26.2 +/- 4.0, respectively, with female (F) diabetic patients more so than male (M). Fasting plasma glucose (mmol l-1) was 12.2 +/- 3.8 vs 5.0 +/- 0.6 in diabetic and normal subjects, and, haemoglobin A1c(%) 9.3 +/- 2.3 vs 5.4 +/- 0.4. Hyperinsulinaemia (mU l-1) was prevalent in both male and female diabetic patients, after adjustment for BMI (geometric mean 1SD interval, M 12.1 (11.8 to 12.4) vs 8.3(7.8 to 8.9) and F 13.3 (12.9 to 13.7) vs 7.4 (7.1 to 7.7). Plasma triglyceride (mmol l-1) was higher in diabetic patients, 1.8 (1.1 to 2.9) vs 1.1 (0.6 to 1.8). Total cholesterol (mmol-1) was slightly elevated in diabetic patients, with females in both populations higher than males, M 5.5 +/- 1.2 vs 5.2 +/- 0.9 and F 5.8 +/- 1.1 vs 5.5 +/- 1.1. HDL cholesterol (mmol l-1) was slightly lower in male and markedly lower in female diabetic patients than in normal subjects, M 1.00 +/- 0.26 vs 1.11 +/- 0.22 and F 1.12 +/- 0.27 vs 1.42 +/- 0.33. Urine albumin was raised in diabetic patients (mg l-1) 16.3 (5.2 to 50.9) vs 7.2 (3.2 to 16.5), as was urine N-acetylglucosaminidase (U l-1 6.4 (3.5 to 11.7) vs 2.9 (1.9 to 4.5) and plasma N-acetylglucosaminidase (U l-1) 11.5 +/- 3.2 vs 10.2 +/- 2.3. Normal subjects aged above 65 years, had slightly higher haemoglobin A1c, insulin, C-peptide, plasma and LDL cholesterol, triglyceride, plasma and urine N-acetylglucosaminidase and lower HDL cholesterol than younger subjects. The 2.5 and 97.5 percentiles for biochemical variables are presented for both populations aged 25-65 years.

Acetylglucosaminidase↗

Diabetes: 'tight control' in a comprehensive treatment plan.

Two out of every five older Americans have abnormal glucose homeostasis. Approximately 1 in 5 has diabetes mellitus, but one-half of these persons are undiagnosed. Treatment of diabetes in older adults is usually managed by primary care physicians. A regular exercise program is the cornerstone of management, even in frail patients. Diet, weight loss, and regular patient education are also important. Age should not limit attempts at tight glucose control in older patients who are cognitively intact and otherwise reasonable candidates. The key to successful management is to follow through with a treatment plan that deals with all of the factors that influence glucose metabolism.

Aftercare↗

Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus.

We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month, and 17 persons received placebo. Before and at the end of the treatment period cholesterol concentration, triglycerides, LDL cholesterol, HDL cholesterol, and plasma and erythrocyte magnesium were evaluated. Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol, and an increase of HDL cholesterol. These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus.

Administration, Oral↗

[Relation between retinopathy and glucose compensation in diabetic children and adolescents].

The fundus of the eye was examined in 302 children and adolescents with insulin dependent diabetes (mean age 14.2 years, SD 3.60, mean duration of diabetes 6.4 years, SD 3.83) by prolonged chromato-ophthalmoscopy and the finding was classified according to the authors' own extended classification of diabetic retinopathy. In 295 patients the authors assessed the mean value of glycosylated protein during the period of 3-6 months before assessment of the retina. When these values were compared with the retinal findings, a statistically highly significant relationship of retinopathy and the glucose compensation of diabetes was found (p < 0.001). The increase of the mean glycoprotein value during adolescence, as compared with the prepubertal period, was also statistically significant, while adolescents without retinopathy had lower mean glycoprotein values as compared with the group as a whole.

Adolescent↗