R A Skyrme-Jones1, I T Meredith. 1. Centre for Heart and Chest Research, Monash Medical Centre and Monash University, Melbourne, Victoria, Australia.
Abstract
BACKGROUND: Elevated levels of soluble adhesion molecules are found in subjects with vascular disease and inconsistently in subjects with conditions predisposing them to atherosclerosis, such as hypercholesterolaemia and diabetes. Oxidized low-density lipoprotein (LDL), protein kinase C and lower than normal levels of NO appear to be important for expression of adhesion molecules, raising the possibility that vitamin E is useful for downregulating levels. We have recently shown that administration of 1000 IU vitamin E for 3 months will improve endothelial vasodilator function (EVF) in uncomplicated type-1 diabetes. OBJECTIVE: To determine whether levels of soluble adhesion molecules in young subjects with uncomplicated diabetes are elevated, whether there is a relationship between levels of soluble adhesion molecule and EVF as well as parameters of diabetes and lipid levels and whether an improvement in EVF related to vitamin E therapy is also associated with a decrease in levels of soluble adhesion molecules. DESIGN: A randomized, placebo-controlled, study. RESULTS: There was no difference between levels of soluble vascular cell adhesion molecule-1 (VCAM-1; 621 +/- 17 versus 635 +/- 37 ng/ml) and P-selectin (59 +/- 2 versus 57 +/- 6 ng/ml) for the diabetic and control groups. For the diabetic cohort, levels of soluble VCAM-1 were inversely related to flow-mediated vasodilatation of the brachial artery (r = -0.41, P < 0.005) and directly related to levels of total cholesterol (r = 0.44, P < 0.005) and LDL cholesterol (r = 0.42, P < 0.01) and duration of diabetes (r = 0.55, P < 0.0005) but there was no relationship with susceptibility of LDL to oxidation or vitamin-E content of LDL. Levels of soluble P-selectin were directly related to duration of diabetes (r = 0.43, P < 0.05) and inversely related to size of LDL particles (r = 0.32, P < 0.05) but were not related to EVF. Vitamin E produced no change in levels of soluble P-selectin and VCAM-1. CONCLUSIONS:Levels of soluble VCAM-1 and P-selectin in young subjects with type-1 diabetes and no evidence of overt vascular disease do not appear to be elevated and are not influenced by vitamin-E supplementation.
RCT Entities:
BACKGROUND: Elevated levels of soluble adhesion molecules are found in subjects with vascular disease and inconsistently in subjects with conditions predisposing them to atherosclerosis, such as hypercholesterolaemia and diabetes. Oxidized low-density lipoprotein (LDL), protein kinase C and lower than normal levels of NO appear to be important for expression of adhesion molecules, raising the possibility that vitamin E is useful for downregulating levels. We have recently shown that administration of 1000 IU vitamin E for 3 months will improve endothelial vasodilator function (EVF) in uncomplicated type-1 diabetes. OBJECTIVE: To determine whether levels of soluble adhesion molecules in young subjects with uncomplicated diabetes are elevated, whether there is a relationship between levels of soluble adhesion molecule and EVF as well as parameters of diabetes and lipid levels and whether an improvement in EVF related to vitamin E therapy is also associated with a decrease in levels of soluble adhesion molecules. DESIGN: A randomized, placebo-controlled, study. RESULTS: There was no difference between levels of soluble vascular cell adhesion molecule-1 (VCAM-1; 621 +/- 17 versus 635 +/- 37 ng/ml) and P-selectin (59 +/- 2 versus 57 +/- 6 ng/ml) for the diabetic and control groups. For the diabetic cohort, levels of soluble VCAM-1 were inversely related to flow-mediated vasodilatation of the brachial artery (r = -0.41, P < 0.005) and directly related to levels of total cholesterol (r = 0.44, P < 0.005) and LDL cholesterol (r = 0.42, P < 0.01) and duration of diabetes (r = 0.55, P < 0.0005) but there was no relationship with susceptibility of LDL to oxidation or vitamin-E content of LDL. Levels of soluble P-selectin were directly related to duration of diabetes (r = 0.43, P < 0.05) and inversely related to size of LDL particles (r = 0.32, P < 0.05) but were not related to EVF. Vitamin E produced no change in levels of soluble P-selectin and VCAM-1. CONCLUSIONS: Levels of soluble VCAM-1 and P-selectin in young subjects with type-1 diabetes and no evidence of overt vascular disease do not appear to be elevated and are not influenced by vitamin-E supplementation.
Authors: Heather K Vincent; Cheryl M Bourguignon; Arthur L Weltman; Kevin R Vincent; Eugene Barrett; Karen E Innes; Ann G Taylor Journal: Metabolism Date: 2009-02 Impact factor: 8.694