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

• Published in: Diabetes care Vol. 29; no. 9; pp. 2064 - 2071
• Main Authors: Stirban, Alin, Negrean, Monica, Stratmann, Bernd, Gawlowski, Thomas, Horstmann, Tina, Götting, Christian, Kleesiek, Knut, Mueller-Roesel, Michaela, Koschinsky, Theodor, Uribarri, Jaime, Vlassara, Helen, Tschoepe, Diethelm
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2006
• Subjects: ACE inhibitors; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - therapeutic use; Age; Biological and medical sciences; Biomarkers - blood; Blood Glucose - analysis; Blood pressure; Cardiovascular disease; Cell adhesion & migration; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic neuropathy; Diabetic retinopathy; Diet therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Food; Glycation End Products, Advanced - administration & dosage; Health aspects; Humans; Hyperglycemia - blood; Hyperglycemia - drug therapy; Hyperglycemia - physiopathology; Hypertriglyceridemia - blood; Hypertriglyceridemia - drug therapy; Hypertriglyceridemia - physiopathology; Hypotheses; Laser-Doppler Flowmetry - methods; Meals; Medical sciences; Medical treatment; Microcirculation - drug effects; Middle Aged; Oxidative Stress - drug effects; Risk factors; Sample size; Thiamine - administration & dosage; Thiamine - analogs & derivatives; Thiamine - therapeutic use; Type 2 diabetes; Vascular Cell Adhesion Molecule-1 - blood; Vascular Diseases - blood; Vascular Diseases - drug therapy; Vascular Diseases - physiopathology; Vitamin B1; Vitamins; Germany; Endocrinopathy; Type 2 diabetes; Human; Oxidative stress; Postprandial; Metabolic diseases; B-Vitamins; Benfotiamine; Glycation; Prevention; Microcirculation; Blood vessel; Endothelial dysfunction; Degradation product
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc06-0531

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.