Dehydroepiandrosterone Administration Counteracts Oxidative Imbalance and Advanced Glycation End Product Formation in Type 2 Diabetic Patients

  1. Enrico Brignardello, MD1,
  2. Cristina Runzo, MD2,
  3. Manuela Aragno, PHD3,
  4. Maria Graziella Catalano, MD4,
  5. Maurizio Cassader, PHD2,
  6. Paolo Cavallo Perin, MD2 and
  7. Giuseppe Boccuzzi, MD14
  1. 1Oncological Endocrinology Unit, San Giovanni Battista Hospital, Turin, Italy
  2. 2Department of Internal Medicine, University of Turin, Turin, Italy
  3. 3Department of Experimental Medicine and Oncology, University of Turin, Turin, Italy
  4. 4Department of Clinical Pathophysiology, University of Turin, Turin, Italy
  1. Address correspondence and reprint requests to Prof. Giuseppe Boccuzzi, Dipartimento di Fisiopatologia Clinica, Via Genova, 3-10126 Torino, Italy. E-mail: giuseppe.boccuzzi{at}


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)-α/TNF-α 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 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-α/TNF-α 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-α/TNF-α 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.


  • Published ahead of print at on 17 August 2007. DOI: 10.2337/dc07-1110.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted August 9, 2007.
    • Received June 22, 2007.
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  1. Diabetes Care vol. 30 no. 11 2922-2927
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