DECREASED SIALIDASE ACTIVITY IN MONONUCLEAR LEUKOCYTES OF TYPE-1 DIABETIC SUBJECTS - RELATIONSHIP TO DIABETIC COMPLICATIONS AND GLYCEMIC CONTROL

Leucocyte surface sialic acid content influences surface charge, defor mability, and leucocyte-endothelial interaction. Abnormal leucocyte st ructure and function contributes both to microvascular damage and diab etic complications. The aim of this study was to investigate altered l eucocyte SA metabolism in diabetic subjects and measure lysosomal sial idase which regulates leucocyte surface sialylation. We examined 26 Ty pe 1 (insulin-dependent) diabetic subjects with retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched normal contro l subjects. Sialidase was assayed in freshly prepared sonicates of pur e mononuclear leucocytes (MNLs), using the fluorometric substrate 4-me thyl-umbelliferyl-N-acetylneuraminic acid. In the subjects with diabet es there was a significant negative correlation between MNL sialidase activity and both HbA(1c) (r(s) = 0.37, p = 0.007) and fructosamine (r (s) = -0.31, p 0.026). MNL sialidase activity was significantly decrea sed in diabetic subjects with clinical evidence of complications compa red to control subjects. HbA(1c) was significantly higher (p = 0.036) in diabetic patients with complications compared to those without. The observed decrease in MNL sialidase activity related to diabetic contr ol may be important in the pathogenesis of vascular damage. Diabetes-a ssociated changes in sialylation of functional cell surface glycoconju gates may have important clinical consequences.