The potential of gliclazide, a sulphonylurea to influence the oxidative processes within the pathogenesis of diabetic vascular disease.
The clinical studies have demonstrated that patients showed significant improvements in their oxidative status after 3 months treatment. This improvement in oxidative status which was associated with a reduction in platelet reactivity, remained constant for the rest of the study period. The effect was independent of glycaemic control. The demonstration of a benefit to clinical vascular disease has proved difficult to achieve in all studies of non-insulin dependent diabetes. This is due to the multifactorial nature of complications and the long duration of disease required before microvascular complications such as retinopathy became apparent. The Japanese Diabetic Retinopathy Program24 studied the progression of retinopathy over a 5 year period comparing Gliclazide with other sulphonylureas and with placebo. The study suggested that with equivalent metabolic control there was a trend towards a lower rate of deterioration of retinopathy and a significantly lower incidence of pre-proliferative retinopathy in the group receiving Gliclazide compared with patients receiving other sulphonylureas or placebo. There is little comparative evidence on the effect of specific sulphonylureas on large vessel disease. Although improvement in parameters of hyperglycaemia is associated with an improvement in morbidity from large vessel disease. In Type II diabetes atherosclerosis coexists in the majority of patients and often predates the clinical diagnosis of diabetes. The presence of atherosclerosis which often determines the ultimate fate of the patient, further increases the level of lipid peroxidation of oxidative stress, amplifying the effects of hyperglycaemia and potentiating vascular damage. In diabetes, therefore where increased glycation and oxidation are fundamental in the pathogenesis of diabetic vascular disease agents such as Gliclazide with anti-oxidant activities may have an enhanced therapeutic role.
Jennings
P E
PE
York Diabetes Centre, York District Hospital, United Kingdom.
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005907:Gliclazide / Q000494:pharmacology* / Q000627:therapeutic use*; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010974:Platelet Aggregation; D011499:Protein Processing, Post-Translational; D012709:Serum Albumin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood
D001786:Blood Glucose; D016166:Free Radical Scavengers; D005907:Gliclazide; D005905:Glyburide; D006442:Glycated Hemoglobin; D008054:Lipid Peroxides; D012709:Serum Albumin; D013482:Superoxide Dismutase