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      Administration of Ascorbic Acid and an Aldose Reductase Inhibitor (Tolrestat) in Diabetes: Effect on Urinary Albumin Excretion

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          The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA<sub>1c</sub>, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) 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 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did 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, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.

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          Urinary glycosaminoglycan excretion in NIDDM subjects: its relationship to albuminura.

          Nephropathy is a serious microvascular complication of diabetes mellitus which is preceded by a period of microalbuminura. Increased loss of proteoglycan (PG) from glomerular basement (GBM) has been postulated to alter glomerular charge selectivity which contributes to urinary loss of albumin. In this study we measured the excretion of urinary glycosaminoglycans (GAG), the degradation products of PG, in 82 non-insulin-dependent (NIDDM) (Type 2) diabetic and 34 non-diabetic subjects. We found that diabetic subjects had a significantly higher GAG urinary excretion rate compared to non-diabetic subjects (12.54 +/- 5.67 vs 8.80 +/- 3.99 micrograms glucuronic acid min-1, p = 0.0001). Categorizing for albuminuric status shows that the diabetic normo-, micro- and macroalbuminuric groups have a higher GAG excretion rate than non-diabetic subjects. Heparan sulphate (HS) GAG urinary excretion was measured in 25 samples from diabetic subjects and 18 non-diabetic subjects. Diabetic subjects excreted more HS GAG than controls both as a rate or as a percentage of total GAG (3.70 +/- 1.94 vs 2.38 +/- 1.48 micrograms glucosamine min-1, p = 0.02; 31.6% +/- 12.5 vs 23.1% +/- 10.4, p = 0.02). Categorizing for albuminuric status shows that micro- and macro-albuminuric groups have a significantly higher HS GAG excretion rate than non-diabetic subjects. We conclude that, as in IDDM, excretion of GAG and HS GAG is higher in NIDDM and may precede the development of microalbuminuria.
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            Cell-Associated Proteoglycans of Retinal Pericytes and Endothelial Cells: Modulation by Glucose and Ascorbic Acid


              Author and article information

              S. Karger AG
              November 1998
              02 November 1998
              : 80
              : 3
              : 277-284
              Departments of a Life Sciences in Nursing and b Medicine, University of Sydney, c Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia
              45187 Nephron 1998;80:277–284
              © 1998 S. Karger AG, Basel

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              Figures: 5, Tables: 4, References: 37, Pages: 8
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