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Old 12-13-2007, 10:17 AM
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Default Alpha Lipoic Acid and Endothelial Function

Objective: Impaired glucose tolerance (IGT) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a very early step in the development of atherosclerosis.

The aim of the present study was to examine ED in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent.

Patients and methods: The study subjects included 42 IGT patients and 26 healthy individuals (control group). The IGT patients were randomly divided into two groups, 21 in each group (the alpha-lipoic acid group and the placebo group).

In the alpha-lipoic acid group, 300 mg of alpha-lipoic acid was administrated before an oral glucose tolerance test (OGTT); in the placebo group, 250 ml of 0.9% sodium chloride was administrated before the OGTT. In addition, 250 ml of 0.9% sodium chloride was also administrated to the control subjects before the OGTT (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load.

High-resolution ultrasound was used to measure flow-mediated endothelium-dependent arterial dilation (FMD) and glyceryltrinitrate (GTN)-induced endothelium-independent arterial dilation.

Results: In the fasting state, and at 60 and 120 min, FMD in both the placebo and alpha-lipoic acid groups was significantly lower than in the controls (P <0> 0.05). In the placebo group, FMD decreased significantly at 60 min after glucose loading (P < 0.01) and increased markedly from 60 to 120 min (P < 0.01).

The alpha-lipoic acid-treated patients showed FMD values intermediate between the control subjects and the IGT patients treated with placebo, at both 60 and 120 min, and the differences were significant (P < 0.01). In multiple regression analysis, FMD was significantly correlated to fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL-C), lipoprotein (a) [Lp(a)], C-reactive protein (CRP), thiobarbituric acid reactive substances (TBARS) and age in IGT patients at baseline (P < 0.01).

Spearman's analysis showed a significant negative correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group) (P < 0.01). There was also a significant correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated with alpha-lipoic acid (P < 0.05), although the power of association decreased.

Conclusion: In subjects with IGT, FMD was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen-derived free radicals. The ED observed after a glucose challenge is related to the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.
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