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.
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.
Stirban
Alin
A
Heart and Diabetes Center NRW, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.
Negrean
Monica
M
Stratmann
Bernd
B
Gawlowski
Thomas
T
Horstmann
Tina
T
Götting
Christian
C
Kleesiek
Knut
K
Mueller-Roesel
Michaela
M
Koschinsky
Theodor
T
Uribarri
Jaime
J
Vlassara
Helen
H
Tschoepe
Diethelm
D
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
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D019010:Vascular Cell Adhesion Molecule-1; D013831:Thiamine; C013835:benphothiamine