Benfotiamine Prevents Macro- and Microvascular Endothelial Dysfunction and Oxidative Stress Following a Meal Rich in Advanced Glycation End Products in Individuals With Type 2 Diabetes

  1. Alin Stirban, MD1,
  2. Monica Negrean, MD1,
  3. Bernd Stratmann, PHD1,
  4. Thomas Gawlowski, MS1,
  5. Tina Horstmann1,
  6. Christian Götting, PHD1,
  7. Knut Kleesiek, MD1,
  8. Michaela Mueller-Roesel, MD1,
  9. Theodor Koschinsky, MD2,
  10. Jaime Uribarri, MD3,
  11. Helen Vlassara, MD3 and
  12. Diethelm Tschoepe, MD1
  1. 1Heart and Diabetes Center NRW, Bad Oeynhausen, Ruhr-University, Bochum, Germany
  2. 2German Diabetes Center, Heinrich-Heine University, Duesseldorf, Germany
  3. 3Division of Diabetes and Aging, Mount Sinai School of Medicine, New York, New York
  1. Address correspondence and reprint requests to Prof. Dr. Diethelm Tschoepe, Heart and Diabetes Center NRW, Georgstrasse 11, 32545 Bad Oeynhausen, Germany. E-mail: dtschoepe{at}


OBJECTIVE— Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now.

RESEARCH DESIGN AND METHODS— Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially.

RESULTS— The HAGE induced a maximum reactive hyperemia decrease of −60.0% after 2 h and a maximum FMD impairment of −35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine.

CONCLUSIONS— Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.


  • A.S. and M.N. contributed equally to this work.

    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. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted June 8, 2006.
    • Received March 9, 2006.
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