Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients

Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100 000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL(2)-CE (r = -0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting slate (P < 0.005), decreased postprandially yet HDL(2)-CE remained unchanged. Postprandial HDL(3) of controls were enriched with phospholipid (PL) (30.3 +/- 2.6% at 6 h) with respect to fasting (25.6 +/- 2.5%, P < 0.01) and to NIDDM-HDL(3) (25.8 +/- 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL(2)-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL(3) with FL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL(3) enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile.