title: Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product 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. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-alpha/TNF-alpha receptor system activity in patients with type 2 diabetes.
  
  
  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 control subjects. 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 control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (+38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (-50%). Moreover, the TNF-alpha/TNF-alpha receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs.
  
  
  CONCLUSIONS
  Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-alpha/TNF-alpha receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.
authors: Oncological Endocrinology Unit, San Giovanni Battista Hospital, Turin, Italy.
authors: Enrico
authors: E
authors: Brignardello
authors: Cristina
authors: C
authors: Runzo
authors: Manuela
authors: M
authors: Aragno
authors: Maria Graziella
authors: MG
authors: Catalano
authors: Maurizio
authors: M
authors: Cassader
authors: Paolo Cavallo
authors: PC
authors: Perin
authors: Giuseppe
authors: G
authors: Boccuzzi
mesh_terms: D003687:Dehydroepiandrosterone / Q000097:blood / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010919:Placebos; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values
chemical_list: D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D005978:Glutathione; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D010919:Placebos; D017382:Reactive Oxygen Species