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Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patients: Roles of pre β-HDL, phospholipid transfer protein and cholesterol esterification

      Abstract

      We tested whether hypertriglyceridemia associated with type 2 diabetes mellitus is accompanied by alterations in pre β-HDL, which are considered to be initial acceptors of cell-derived cholesterol, and by changes in the ability of plasma to promote cellular cholesterol efflux. In 28 hypertriglyceridemic and 56 normotriglyceridemic type 2 diabetic patients, and in 56 control subjects, we determined plasma lipids, HDL cholesterol and phospholipids, plasma pre β-HDL and pre β-HDL formation, phospholipid transfer protein (PLTP) activity, plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) and the ability of plasma to stimulate cholesterol efflux out of cultured human fibroblasts. HDL cholesterol and HDL phospholipids were lower, whereas plasma PLTP activity, EST and CET were higher in hypertriglyceridemic diabetic patients than in the other groups. Pre β-HDL levels and pre β-HDL formation were unaltered, although the relative amount of pre β-HDL (expressed as % of total plasma apo A-I) was increased in hypertriglyeridemic diabetic patients. Cellular cholesterol efflux to plasma from hypertriglyceridemic diabetic patients was increased compared to efflux to normotriglyceridemic diabetic and control plasma, but efflux to normotriglyceridemic diabetic and control plasma did not differ. Multiple linear regression analysis demonstrated that cellular cholesterol efflux to plasma was positively and independently related to pre β-HDL formation, PLTP activity and EST (multiple r = 0.48), but not to the diabetic state. In conclusion, cholesterol efflux from fibroblasts to normotriglyceridemic diabetic plasma is unchanged. Efflux to hypertriglyceridemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre β-HDL formation in diabetic hypertriglyceridemia, despite low apo A-I, could contribute to maintenance of cholesterol efflux.

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