The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance.

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 < 0.01). In the control group, FMD tended to decrease at 60 min after glucose loading and returned to the baseline levels at 120 min (P > 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.