Reticulocyte counts and haemoglobin glycosylation in diabetes.
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Biomedical subjects
Publications and source records attributed to P Dello Russo.
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Antithrombin III activity was moderately but significantly decreased in insulin dependent diabetics (p less than 0.005), while no difference has been found between the diabetic (n = 25) and control groups (n = 22) in antithrombin III plasma concentration. Moreover, antithrombin III activity was inversely correlated with glycosylated plasma proteins (r = 0.57; p less than 0.01). These data show that in diabetes there is a depressed biological activity of antithrombin III and suggest that this reflects nonenzymatic glycosylation of antithrombin III protein.
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The serum concentrations of different glycosaminoglycan fractions have been studied in diabetic subjects without evidence of vascular complications and compared with those of age-and sex-matched normal subjects. Electrophoretic analysis of the various glycosaminoglycan fractions showed an increase in hyalunoric acid and heparin, and a decrease in heparan sulfate, chondroitin-4-sulfate and chondroitin-6-sulfate. Furthermore, the levels of glycosylated haemoglobin A1 were positively correlated with those of hyaluronic acid (r = 0.96, p. less than 0.001) and heparin (r = 0.45, p less than 0.01) in the diabetic group. The present data suggest thah a) in diabetics there is a shift in the metabolism of glycosaminoglycans towards a decreased sulfated glycosaminoglycans/hyaluronic acid ratio; and b) long-lasting hyperglycemia is correlated with the disturbances in the metabolism of glycosaminoglycans.
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Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.
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The effects of metabolic control on both antithrombin III (AT III) activity and AT III plasma concentration in 20 insulin-treated diabetic subjects have been evaluated. Basal AT III activity was significantly lower in diabetic subjects versus healthy controls (P less than 0.001), whereas no difference was found in AT III concentration. A good correlation was found between AT III activity and AT III concentration (r = 0.81; P less than 0.001) in healthy controls, but this correlation was not significant in diabetic subjects (r = 0.12; P = NS). In those subjects a linear inverse correlation was found to exist between AT III activity and level of glycosylated proteins (r = -0.43; P less than 0.05). Diabetic subjects were also examined after 1 and 2 mo of restored metabolic control, obtained by human insulin (DNA-recombinant) therapy. Improved metabolic control was characterized by an increase of AT III activity (P less than 0.05), a decrease of mean daily blood glucose, and stable HbA1 and glycosylated proteins (P less than 0.05), while AT III concentration did not vary. On the other hand, a significant inverse correlation between AT III activity and glycosylated proteins was found during both the first and second months (r = -0.54 and r = -0.53, respectively; P less than 0.01). Moreover, no correlation between AT III activity and AT III concentration was found. These data suggest that impaired metabolic control may alter the biologic activity of AT III in diabetes, but not its plasma concentration.
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Human plasma albumin was incubated in 25 mM/l glucose at 37 degrees C for up to sevent days. Aliquots of this mixture were also incubated with alpha-tocopherol (Vitamin E) at 2 mg/dl, 4 mg/dl and 8 mg/dl, respectively. Vitamin E inhibited protein glycation and, furthermore, shows a dose-dependent effect. This report suggests the possibility of using Vitamin E, at therapeutic doses, to obtain the inhibition of non-enzymatic glycation.