Lipid transfer proteins: consequences for cellular cholesterol efflux and cardiovascular risk in diabetes mellitus

This thesis studies the changes in the ability of plasma to stimulate cellular cholesterol efflux in type 1 and type 2 diabetes mellitus and the alterations in lipid metabolism mediated by lipid transfer proteins and its risk of cardiovascular disease in type 2 diabetes mellitus. Efflux to plasma from moderately hypercholesterolaemic type 1 diabetes patients is enhanced, probably due to an increased apo A-I, HDL phospholipids and PLTP activity. Simvastatin increases HDL cholesterol via lowering of plasma cholesteryl ester transfer. The HDL changes after simvastatin do not increase cellular cholesterol further. Reduction in dietary saturated fat and cholesterol intake does not adversely affect cellular cholesterol efflux to plasma from type 1 diabetic patients, despite a drop in pre β-HDL formation. Efflux to hypertriglyceridaemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre β-HDL formation in diabetic hypertriglyceridaemia, despite low apo A-I, could contribute to maintenance of cellular cholesterol efflux. Plasma CET is a positive determinant of IMT in type 2 diabetes mellitus and control subjects. Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at higher triglycerides. Plasma PLTP activity is a positive determinant of IMT in type 2 diabetes mellitus, suggesting that high PLTP activity is involved in accelerated atherosclerosis in this disease. Specific CETP activity is decreased in type 2 diabetes mellitus. Specific PLTP activity is higher in diabetes, as a result of the association of plasma PLTP activity with plasma triglycerides and obesity.