Summary
Lysosomal enzymes degrade membrane glycoconjugates, and increased circulating enzyme activity may be an important mechanism in the pathogenesis of diabetic microangiopathy. We have assayed a profile of seven lysosomal enzyme activities (nmol·h−1·ml−1) in platelet-free plasma from 54 Type 1 (insulin-dependent) diabetic subjects (median age 31 years) and 42 matched normal control subjects. A significant increase in median (interquartile range) enzyme activity was measured in diabetic compared to control subjects for β-d-glucuronidase, 121 (97.7–171) vs 88.8 (62.8–113), p <0.001; β-d-Nacetylglucosaminidase, 693 (568–799) vs 568 (462–686), p <0.001; α-d-mannosidase, 23.8 (16.7–28.9) vs 14.5 (10.1–20.0), p <0.001; and β-d-galactosidase, 6.94(6.11–9.99) vs 6.66(4.78–8.33), p <0.04. In contrast, α-l-fucosidase, α-d-galactosidase and β-d-mannosidase activities were similar in diabetic and control subjects. None of the enzyme activities differed significantly (p <0.05) between 24 diabetic patients with clinical complications and 30 complication-free diabetic patients with similar glycaemic control which does not support the hypothesis that enzyme increases in diabetes arise simply by leakage from damaged tissues. In the diabetic subjects HbA1, median (interquartile range) 9.10 (7.40–10.60), was significantly related to β-d-glucuronidase (r s = 0.56, p <0.001) and β-d-Nacetylglucosaminidase (r s = 0.55, p <0.001). We have therefore demonstrated in diabetic subjects an increase in certain lysosomal glycosidases, that correlates with glycaemic control. Such increased enzyme activities acting on endothelial and basement membrane substrates may reduce glycoconjugate content, modify charge density, and thereby influence membrane permeability, a hallmark of microangiopathy.
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Waters, P.J., Flynn, M.D., Corrall, R.J.M. et al. Increases in plasma lysosomal enzymes in Type 1 (insulin-dependent) diabetes mellitus: relationship to diabetic complications and glycaemic control. Diabetologia 35, 991–995 (1992). https://doi.org/10.1007/BF00401431
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DOI: https://doi.org/10.1007/BF00401431