title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Heart and Diabetes Center NRW, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.
authors.forename: Alin
authors.initials: A
authors.lastname: Stirban
authors.forename: Monica
authors.initials: M
authors.lastname: Negrean
authors.forename: Bernd
authors.initials: B
authors.lastname: Stratmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Gawlowski
authors.forename: Tina
authors.initials: T
authors.lastname: Horstmann
authors.forename: Christian
authors.initials: C
authors.lastname: Götting
authors.forename: Knut
authors.initials: K
authors.lastname: Kleesiek
authors.forename: Michaela
authors.initials: M
authors.lastname: Mueller-Roesel
authors.forename: Theodor
authors.initials: T
authors.lastname: Koschinsky
authors.forename: Jaime
authors.initials: J
authors.lastname: Uribarri
authors.forename: Helen
authors.initials: H
authors.lastname: Vlassara
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000008:administration & dosage*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D013831:Thiamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014652:Vascular Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D019010:Vascular Cell Adhesion Molecule-1; D013831:Thiamine; C013835:benphothiamine