Summary. Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor 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 gmol/1, 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 ~tmol/1), 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.Key words: Ascorbic acid, dehydroascorbic acid, diabetes mellitus, free radical activity, oxidative stress.Reduced levels and altered metabolic turnover of ascorbic acid (AA, vitamin C) have been reportedin severaltissues in experimen tally induced diabetes [1-3] and in diabeticpatients [4]. There are reports that high dose vitamin C regimens are associated with reversal of early signs of retinopathy [5] and normalisation of capillary strength in diabetes mellitus [6]. In the elderly non-diabetic population AA is often deficient and may be correctable by supplementation [7] -this problem might be of particular significance in elderly diabetic patients who are reported to show more rapid progress of some diabetic complications [8].Ascorbic acid functions as an important component of cellular defence against oxygen toxicity and lipid peroxidation caused by free radical mechanisms [9,10]. During scavenging of free radicals it is converted to dehydroascorbic acid, DHA, in serum and in the mitochondrial fractions of various tissues [11]. It is also a co-factor in the biosynthesis and post-translational modification of collagen...

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Clinical significance of fever in the systemic lupus erythematosus patient receiving steroid therapy.Background. Active systemic lupus erythematosus (SLE) can cause fever. Steroids (glucocorticoids) suppress SLE fever; however, the extent to which steroid therapy affects SLE fever not previously been rigorously studied.Methods. Study A is a prospective study of recurrently active SLE patients (N = 92, 60 renal SLE and 32 nonrenal SLE) who recorded daily oral evening temperatures while participating in a longitudinal study of risk factors for SLE flare. Study B is a retrospective study of consecutive febrile SLE patients (N = 22) who received steroids initially because SLE was suspected. At final analysis 11 had SLE fever and 11 had infection fever.Results. In study A during a mean follow-up of 13.2 ± 8.1 months, 51 of the 92 patients experienced 73 SLE flares. In only one patient was SLE fever associated with SLE flare. In the other 50 patients who flared, there was no significant trend to develop fever prior to or at the onset of SLE flare. Prednisone, median dose 10 mg, was being received at 82% of the study visits at which an SLE flare was declared. In study B, prednisone 28 mg (range 20 to 40 mg) completely suppressed SLE fever, usually within 24 hours. In contrast, infection fever persisted despite prednisone 35 to 300 mg/day. Of those with infection fever, three developed fatal sepsis when high-dose steroid therapy was continued.Conclusion. In SLE patients receiving prednisone at maintenance doses or greater, SLE fever is rare. When fever does develop, it is usually due to infection. Continuing high steroid dose steroid therapy in those with infection fever may increase the risk of severe sepsis.Fever is believed to be a common manifestation of active systemic lupus erythematosus (SLE) fever.

Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.