ALTERATIONS IN COMPOSITION AND CONCENTRATION OF LIPOPROTEINS AND ELEVATED CHOLESTERYL ESTER TRANSFER IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM)

Cholesteryl esters (CE) exchange between lipoproteins through the acti on of cholesteryl ester transfer protein (CETP). Situations at high ri sk for atherosclerosis are often accompanied by an accelerated net mas s CE transfer (CET) from high density lipoproteins (HDL) to very low ( VLDL) and low density lipoproteins (LDL). However, the question as to whether the net mass CET is increased or decreased in non-insulin-depe ndent diabetes mellitus (NIDDM) has led to controversial data. To clar ify this point, we have undertaken a detailed study of CET in 105 NIDD M patients by comparison with 17 control subjects. Net mass CET was ap proximately doubled in NIDDM. Plasma CETP activity and unidirectional CET from HDL to VLDL + LDL (CET(HDL + VLDL + LDL)) or from VLDL + LDL to HDL(CET?(VLDL + LDL --> HDL)) were measured under controlled lipopr otein concentrations using radioisotopic assays. No difference was obs erved in plasma CETP activity between NIDDM and controls. In NIDDEVI, CET(HDL --> VLDL + LDL) and CET(VLDL + LDL --> HDL), were decreased by 25% and 20%, respectively, as a consequence of alterations in lipopro tein compositions. Net mass CET was highly correlated with plasma trig lyceride (TG) concentration (r = 0.66, P < 0.001) but not with that of LDL-cholesterol (r = 0.06, P > 0.6). When TG levels were decreased fo llowing dietetic recommendations or insulinotherapy, the net mass CET was lowered accordingly. We conclude that net mass CET is accelerated in NIDDM in spite of a decreased unidirectional CE(THDL --> VLDL + LDL ). This results from a lowered CET(VLDL + LDL --> HDL) and from elevat ed TG concentration, and the latter probably reflects a concentration effect of VLDL.