GLYCOSAMINOGLYCAN EXCRETION IN DIABETES-MELLITUS - RELATION WITH ATHEROSCLEROSIS AND GLOMERULOSCLEROSIS

The prevalence of nephropathy and atherosclerosis is elevated in diabetes. Both complications could result from a common alteration in the composition of extracellular matrix including some derangement in glycosaminoglycan metabolism. In order to gain further insight into the mechanism leading to athero and glomerulosclerosis in the course of diabetes, we measured serum cholesterol, microalbuminuria and three urinary markers of the extracellular matrix catabolism (total glycosaminoglycans, chondroitin sulfates, hydroxyproline) in 71 diabetic patients. Patients were stratified for known type of diabetes (Type I, n=43 - Type II, n=28) or for presence of the following risk factors: albuminuria >30 mg/d (subset 1, n=12); poor metabolic control (subset 2, n=21); diabetes duration >20 yr (subset 3, n=9) and cholesterolemia >6.15 mmol/l (subset 4, n=21). Normalized to creatininuria, glycosaminoglycan and chondroitin sulfate excretion rates were similar in all groups of diabetics. Strong correlations were observed between chondroitin sulfate excretion rates and cholesterolemia in patients of subsets 1 (r=0.71, p<0.02), and 4 (r=0.77, p<0.001). In this latter group, the proportion of urinary CSs (CSs/total GAGs) was also strongly correlated with cholesterolemia (r=0.79, p<0.001) and to a smaller extend with the diabetes duration (r=0.51, p<0.02). It is concluded that glomerulosclerosis and atherosclerosis development in diabetes could be accompanied by a modified pattern of glycosaminoglycan synthesis with increase of chondroitin sulfate synthesis.