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 100000 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 HDL₂-CE (r= −0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL₂-CE remained unchanged. Postprandial HDL₃ 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-HDL₃ (25.8 ± 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL₂-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL₃ with PL, 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 HDL₃ 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.