Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study

Oxidative stress plays a central role in the pathogenesis and progression o f late microangiopathic complications (diabetic nephropathy) in diabetes me llitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha -lipoic acid reduce oxidative stress and urinary alb umin excretion. In this prospective, open and non-randomized study, the eff ect of alpha -lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma t hrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months. Forty-nine patients (34 wit h Type 1 diabetes, 15 with Type 2 diabetes) had no antioxidant treatment an d served as a control group. Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were treated with 600 mg alpha -lipoic acid per d ay. Only patients with an urinary albumin concentration < 200 mg/l were inc luded into the study. After LS months of follow up, the plasma thrombomodul in level increased from 35.9 <plus/minus> 9.5 to 39.7 +/- 9.9 ng/ml (P < 0. 05) in the control group. In the <alpha>-lipoic acid treated group the plas ma thrombomodulin level decreased from 37.5 +/- 16.2 to 30.9 +/- 14.5 ng/ml (P < 0.01). The UAC increased in patients without <alpha>-lipoic acid trea tment from 21.2 +/- 29.5 to 36.9 +/- 60.6 ng/l (P < 0.05), but was unchange d with <alpha>-lipoic acid. It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alp ha -lipoic acid treated group is due to antioxidative effects of alpha -lip oic acid: and if so that oxidative stress plays a central role in the patho genesis of diabetic nephropathy. Furthermore, progression of the disease mi ght be inhibited by antioxidant drugs. A placebo-controlled study is needed . (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.