DISTURBED HANDLING OF ASCORBIC-ACID IN DIABETIC-PATIENTS WITH AND WITHOUT MICROANGIOPATHY DURING HIGH-DOSE ASCORBATE SUPPLEMENTATION

Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a co-factor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p < 0.01, vs 82.9 +/- 30.9-mu-mol/l, p < 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p < 0.01, vs 0.38 +/- 0.14, p < 0.001). At three weeks, ascorbate concentrations rose in all groups (p < 0.0001) and was maintained in control subjects (151.5 +/- 56.3-mu-mol/l), but fell in both diabetic groups by six weeks (p < 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p < 0.0001) but rose again in the diabetic groups by six weeks (p < 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p < 0.05). No significant changes were observed in fructosamine concentrations in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.