Alterations of glycosaminoglycan metabolism in the development of diabetic complications in relation to metabolic control

Abstract

Disturbed metabolism of glycosaminoglycans (GAGs) has been proposed to play an important role in the pathogenesis of late diabetic complications. The effect of diabetic complications and metabolic control on both total serum GAGs content and the serum activity of lysosomal glycosidases (N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase, beta-D-galactosidase, and alpha-D-mannosidase) contributing to GAGs degradation, was investigated in 48 patients with type 2 diabetes mellitus. The activity of beta-D-glucosidase and acid phosphatase, the lysosomal enzymes unrelated to GAGs metabolism, was determined for comparison. The elevated serum total GAG concentration in diabetic patients was strongly and positively influenced by poor metabolic compensation of diabetes and the presence of vascular complications. A similar tendency has been shown in regard to the activity of enzymes involved in GAG degradation, especially N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and beta-D-galactosidase. Furthermore, the total serum GAG concentrations, as well as the activity of lysosomal enzymes involved in the extracellular matrix degradation, closely followed metabolic compensation, regardless of diabetic vascular complications. Thus, we suggest that increased values of the investigated parameters may indicate the degree of endothelial cell dysfunction and may be useful to predict the development of diabetic vascular pathology.