ADMINISTRATION OF ASCORBIC-ACID AND AN ALDOSE REDUCTASE INHIBITOR (TOLRESTAT) IN DIABETES - EFFECT ON URINARY ALBUMIN EXCRETION

The important role of ascorbic acid (AA) as an anti-oxidant is particu larly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treat ment with AA or an aldose reductase inhibitor, tolrestat, on AA metabo lism and urinary albumin excretion in diabetes. Blood and urine sample s were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subject s who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA(1 c), plasma lipids, urinary albumin, and total glycosaminoglycan excret ion were measured at all time points, and heparan sulphate (glycosamin oglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 dia betes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excre tion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but d id not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon's signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhi bition of aldose reductase did not normalize plasma AA or AER in human s. In fact, tolrestat reduced the plasma AA concentration, a phenomeno n which may be due to increased utilization of AA. Dietary supplementa tion of AA in diabetic subjects may have longterm benefits in attenuat ing the progression of diabetic complications.