THE ROLE OF DIETARY-CHOLESTEROL IN THE REGULATION OF POSTPRANDIAL APOLIPOPROTEIN B48 LEVELS IN DIABETES

The atherogenicity of intestinally derived postprandial lipoproteins h as been confirmed in a number of recent studies. We have shown abnorma lities in postprandial lipoprotein metabolism in diabetic patients, a group with an increased susceptibility to atherosclerosis. This study examined the relationship between dietary cholesterol and the postpran dial, intestinally derived, apolipoprotein B48 and apolipoprotein B100 from the liver. We compared 10 non-insulin-dependent (Type 2, NIDDM) diabetic patients and 10 age-matched non-diabetic control subjects. Ea sting blood was taken and subjects were fed a cholesterol-free, high f at meal. Blood samples were repeated at 2 h, 4 h, 6 h, and 8 h postpra ndial. The following week fasting blood was collected and subjects wer e given the same meal with Ig of added cholesterol. Blood was collecte d at the same time points. Chylomicrons and very low density lipoprote in were isolated by sequential ultracentrifugation and their lipoprote in composition determined. Apolipoproteins B48 and B100 were separated by gradient gel electrophoresis and quantified by densitometric scann ing using a low density lipoprotein apolipoprotein B100 standard. Post prandial chylomicron cholesterol and triglyceride increased after the high cholesterol meal in both groups (p < 0.001). The postprandial ch ylomicron apolipoprotein B48 response of both diabetic and control sub jects to the cholesterol meal was less than to the cholesterol-free me al (p < 0.001). Fasting very low density lipoprotein apolipoprotein B4 8 was higher in diabetic patients compared to control subjects and the ir postprandial increase following the cholesterol-free meal was signi ficantly greater (p<0.001). There was a 10-fold increase in the increm ental postprandial VLDL apolipoprotein B48 area under the curve after the cholesterol-rich meal in the diabetic patients compared to a 3-fol d increase in control subjects. The postprandial very low density lipo protein apolipoprotein B100 was similar in the two groups with both me als. The study demonstrates a very significant increase in the amount of intestinally derived small apolipoprotein B48-associated particles in the very low density lipoprotein fraction following a cholesterol-r ich meal in diabetic patients. Synthesis rather than clearance may be the major cause of the increase in these atherogenic postprandial part icles. (C) 1997 by John Wiley & Sons, Ltd.