Does benfotiamine reduce serum levels of advanced glycation end products and biochemical markers of vascular dysfunction in type 1 diabetes?

Background: Despite intensive efforts to improve glycemic control, diabetic patients are still at a markedly increased risk of microvascular complications associated with long-term hyperglycemia. Advanced glycation end prodcuts (AGEs) are thought to play a central role in the pathophysiology of these complications. Benfotiamine, a lipid soluble form of thiamine, has been recently shown to prevent formation of AGEs in diabetic rats. This effect is due an increased activity of the thiamine dependent enzyme transketolase. Our study will thus examine the biochemical effects of benfotiamine supplementation in type 1 diabetics. Study design: The study will be carried out as a parallel randomised double-blind placebo controlled prospective trial of 12 months du ration involving a total of 80 microalbuminuric type 1 diabetic patients (urinary albumin excretion > 15 ug/min overnight urine). The patients will be recruited over an 8-month period. 40 patients will be randomised (using random number generator on comp uter) to the active arm and 40 to the placebo arm. Patients in the active group will be given 450 mg benfotiamine per day (Benfogamma®, Wörwag Pharma GmbH, Stuttgart, Germany). Patients in the placebo group will be provided with placebo tablets matched for size, colour and taste. Neither the physician administering the tablets or the patient will be made aware of the content. Compliance in both groups will be measured by both tablet count and serum thiamine concentrations at each time point. Blood sa mpling/urine samples/clinical evaluations will be performed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months. This project has already been approved by the Regional Ethics Committee (East Noway 08 March 2004). We are awaiting approval by Statens Legemiddelverk.