Effect van de toediening van foliumzuur op de endotheelfunctie bij type II diabetes mellitus
01 / 2002 - 01 / 2006
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. The atherogenic effects of hyperhomocysteinemia may be preceded by endothelial dysfunction. There is no gold standard for measuring endothelial dysfunction. Measurement of vWF in plasma is an accepted method. New markers of endothelial dysfunction are the adhesion molecules (sVCAM-1, ICAM-1 and E-selectin). Significant relationships have been shown of soluble CAMs with atherosclerosis and cardiovascular events, and increasing evidence supports the role of soluble CAMs as molecular markers of atherosclerosis. Microalbuminuria is a strong predictor of cardiovascular morbidity and mortality. The pathophysiological basis of the association of microalbuminuria and cardiovascular disease is unclear, but endothelial dysfunction may be the missing link. Microalbuminuria and hyperhomocysteinemia are both associated with an increase of the vWF concentration, and sVCAM-1 levels are associated with the development of microalbuminuria. Studies addressing the association of hyperhomocysteinemia and microalbuminuria are not entirely consistent, but suggest that increased homocysteine levels are associated with an increased prevalence of microalbuminuria, as recently confirmed by Jager et al. in a prospective study. If hyperhomocysteinemia causes endothelial dysfunction, it may be that reduction of hyperhomocysteinemia by folic acid improves endothelial dysfunction. This could be reflected in reduction of microalbuminuria and of plasma levels of vWF and sCAMS. In this study we examine the effect of intervention with folic acid on microalbuminuria, vWF and sCAMs in patients with diabetes mellitus type 2 and mild hyperhomocysteinemia. These patients are divided into 2 groups, matched for sex and age, stratified for previous cardiovascular events and lipid status, and randomised for treatment with folic acid once a day 5 mg or placebo. After 0, 3, and 6 months the difference will be determined between the folic acid group and the placebo group with regard to fasting homocysteine, vWF antigen concentration, sCAMs, interleukin-6, TNF-alpha, and urinary microalbumin/creatinine ratio. 53 patients have participated, of whom 9 patients were excluded due to change of medication or loss in follow-up. Blood biochemical analyses are performed at this time.