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.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 Ϫ60.0% after 2 h and a maximum FMD impairment of Ϫ35.1% after 4 h, without affecting endotheliumindependent 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. Diabetes Care 29:2064 -2071, 2006E ndothelial dysfunction is an early marker of atherosclerosis and accompanies states showing a high cardiovascular risk, such as smoking (1), dyslipidemia (2), arterial hypertension (3), obesity (4), coronary artery disease (5), congestive heart failure (6), and type 1 (7) and type 2 (8) diabetes. Postprandial endothelial dysfunction has been proposed as the link between postprandial dysmetabolism and atherosclerosis (9) and occurs not only in patients with cardiovascular disease (10) or diabetes (11) but even in healthy subjects (12). Distinctive and cumulative (11) effects of hyperglycemia (13) and hypertriglyceridemia (14) on postprandial endothelial dysfunction have been shown. Since the postprandial state covers most of our daytime, interventions aimed at reducing postprandial endothelial dysfunction might play a decisive role in prevention of atherosclerosis. Several therapeutic approaches have been suggested for the treatment of postprandial endothelial dysfunction, including insulin, folic acid, tetrahydrobiopterin, vitamins C and E, and statins (11). These approaches aim at reducing postprandial oxidative stress (vitamins C and E, statins, and partly folic acid), postprandial hyperglycemia (insul...

Adiponectin Decreases Postprandially Following a Heat-Processed Meal in Individuals With Type 2 Diabetes

“…We have previously shown that benfotiamine prevents postprandial increase in oxidative stress, AGEs (20), and endothelial dysfunction. We suggest that similar mechanisms reduce postprandial adipocyte stress, thus preventing adiponectin decrease.…”

“…Advanced glycation end products (AGEs) (16) play a major role in the development of diabetes complications (17). We have shown that dietary AGEs acutely impair endothelial function (18,19), an effect counteracted by benfotiamine (20), a transketolase activator that blocks several hyperglycemiainduced pathways, including the formation of AGEs (21). AGEs might interact with adipocytes through AGE receptors (22) and induce cellular dysfunction via generation of reactive oxygen species (23), a pathway probably responsible for the AGE-induced downregulation of leptin secretion in vitro (24).…”

Impact of Diet Composition on Blood Glucose Regulation

“…Benfotiamine, a lipid-soluble allithiamine derivative that has better intestinal absorption and improved bioavailability than thiamine, has been shown to afford postprandial benefit on vascular function following meals rich in advanced glycation end-products in T2DM. Plasma glucose levels were lowered in the benfotiamine supplemented group but not significantly in the postprandial period after and AGE meal (Stirban et al, 2006), but the effects of benfiotamine on PPG were significant after a cooked meat meal (Stirban et al, 2007). The pharmacologic effects of niacin (nicotinic acid; vitamin B3) on cholesterol lowering were first reported in 1955 (Altschul et al, 1955).…”

Diabetic Nephropathy: Current and Novel Therapeutic Approaches to Prevent Its Development and Progression

“…In addition, pyridoxamine, an intermediate of vitamin B 6 , attenuated the progression of human diabetic nephropathy and concurrently reduced AGE and urinary TGF- (Williams, Bolton et al 2007). Furthermore, benfotiamine (liposoluble vitamin B1 derivative), decreases AGE accumulation, inflammation and improves vascular function in type 2 diabetic patients consuming diets high in AGE content (Stirban, Negrean et al 2006). To date there have been three clinical trials conducted which employed AGE-lowering therapies .…”