We tested whether
hypertriglyceridemia associated with
type 2 diabetes mellitus is accompanied by alterations in
pre beta-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 beta-HDL and
pre beta-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 beta-HDL levels and
pre beta-HDL formation were unaltered, although the relative amount of
pre beta-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 beta-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 beta-HDL formation in diabetic
hypertriglyceridemia, despite low
apo A-I, could contribute to maintenance of
cholesterol efflux.