Dehydroepiandrosterone administration counteracts oxidative imbalance and AGE formation in type 2 diabetic patients

Abstract

Objective: Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several “in vivo” and “in vitro” models. The study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration and TNFα/TNFα receptor system activity in patients with type 2 diabetes.

Research Design and Methods: Twenty patients were enrolled in the study and randomly assigned to the DHEA (n = 10) or placebo (n = 10) group. Twenty healthy sex- and age-matched subjects with normal glucose levels served as controls. DHEA was given as a single daily dose of 50 mg, for 12 weeks.

Results: Oxidative stress parameters were significantly higher in diabetic patients versus controls. Pentosidine levels, as well as sTNF-RI and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of ROS and HNE dropped by 53% and 47% respectively, whereas the non-enzymatic antioxidants GSH and Vitamin E increased (+ 38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMC). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (- 50%). Moreover, the TNFα/TNFα receptor system was shown to be less activated after DHEA treatment, both in plasma and in PBMC.

Conclusions: Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycaemia, down-regulates the TNFα/TNFα receptors system and prevents AGE formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.