title: Decreased sialidase activity in mononuclear leucocytes of type 1 diabetic subjects: relationship to diabetic complications and glycaemic control.
abstract: Leucocyte surface sialic acid content influences surface charge, deformability, and leucocyte-endothelial interaction. Abnormal leucocyte structure and function contributes both to microvascular damage and diabetic complications. The aim of this study was to investigate altered leucocyte SA metabolism in diabetic subjects and measure lysosomal sialidase which regulates leucocyte surface sialylation. We examined 26 Type 1 (insulin-dependent) diabetic subjects with retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched normal control subjects. Sialidase was assayed in freshly prepared sonicates of pure mononuclear leucocytes (MNLs), using the fluorometric substrate 4-methyl-umbelliferyl-N-acetylneuraminic acid. In the subjects with diabetes there was a significant negative correlation between MNL sialidase activity and both HbA1c (rs = 0.37, p = 0.007) and fructosamine (rs = -0.31, p = 0.026). MNL sialidase activity was significantly decreased in diabetic subjects with clinical evidence of complications compared to control subjects. HbA1c 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 control may be important in the pathogenesis of vascular damage. Diabetes-associated changes in sialylation of functional cell surface glycoconjugates may have important clinical consequences.
authors.affiliation: Department of Biochemistry, Bath University, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Waters
authors.forename: M D
authors.initials: MD
authors.lastname: Flynn
authors.forename: C A
authors.initials: CA
authors.lastname: Pennock
authors.forename: R J
authors.initials: RJ
authors.lastname: Corrall
authors.forename: R J
authors.initials: RJ
authors.lastname: Greenwood
authors.forename: R
authors.initials: R
authors.lastname: Eisenthal
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000201:enzymology*; D003925:Diabetic Angiopathies / Q000097:blood* / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000097:blood / Q000201:enzymology; D005260:Female; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D009439:Neuraminidase / Q000097:blood*; D012016:Reference Values; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D019270:Fructosamine; D006442:Glycated Hemoglobin; D006595:Hexosamines; D009439:Neuraminidase