Effects of eparlestat on plasma levels of advanced glycation end products in patients with type 2 diabetes.

Advanced glycation end products (AGE) are produced by a nonenzymatic reaction between glucose and proteins in the plasma of diabetic patients. Recently, AGE have been reported to promote and accelerate diabetic complications and atherosclerosis. The activity of aldose reductase (AR) is increased in diabetic patients. AGE are reported also to be produced by increased levels of fructose through increased activity of AR in diabetes. Consequently, we administered eparlestat, one of AR inhibitors, to diabetic patients and investigated the plasma carboxymethyl-lysine (CML) concentration, one of the AGE, before and after the administration of eparlestat. Though plasma CML concentration did not show any significant changes in all patients after the administration of eparlestat in the present study (from 2.7 +/- 0.3 mU/mL to 2.5 +/- 0.2 mU/mL; 3 months, 2.9 +/- 0.3 mU/mL; 6 months), plasma CML concentration were significantly decreased 3 months after the administration of eparlestat in the patients whose CML concentration before the treatment was higher than 3 mU/mL (from 3.4 +/- 0.2 mU/mL to 2.6 +/- 0.2 mU/mL; 3 months, p = 0.017). Serum thrombomodulin and HbA1c levels did not show any significant changes. These results suggest that the administration of eparlestat may be beneficial in preventing diabetic complications by decreasing plasma CML in diabetic patients.