Postprandial apolipoprotein B48-and B100-containing lipoproteins in type 2diabetes: Do statins have a specific effect on triglyceride metabolism?

There is little information about the effect of an alteration of low-densit y lipoprotein (LDL) turnover on chylomicron and very-low-density lipoprotei n (VLDL) metabolism, yet chylomicron remnant particles are thought to be pa rticularly atherogenic, This study examined the effect of inhibition of cho lesterol synthesis on postprandial lipoproteins. Eight type 2 diabetic pati ents were examined before treatment with the 3-hydroxy-3-methyl glutaryl co enzyme A (HMGCoA) reductase inhibitor cerivastatin, after 4 weeks on active treatment, and 4 weeks after stopping treatment. On each occasion, blood w as collected fasting and at 2-hour intervals for up to 8 hours after a high -fat meal. Chylomicrons and VLDLs were isolated by sequential ultracentrifu gation. Compositional analysis was performed including the measurement of a polipoprotein B48 (apo B48) and apo B100 using polyacrylamide gradient gel electrophoresis, During statin treatment, there was a significant reduction in the postprandial chylomicron apo B48 area under the curve (AUC) from 23 +/- 16 to 17 +/- 10 (P < .01) and apo B100 in the chylomicron fraction fro m 166 +/- 148 to 70 +/- 70 (P < .05). Postprandial cholesterol (362 +/- 193 to 74 +/- 39, P < .005), triglyceride (2,222 +/- 1,440 to 746 +/- 329), an d phospholipid (518 +/- 267 to 205 +/- 94) also decreased (P < .005). In th e VLDL fraction, the postprandial cholesterol and triglyceride AUC were sig nificantly reduced by statin (316 +/- 228 to 171 +/- 78, P < .05, and 1,733 +/- 833 to 857 +/- 468, P < .02, respectively). Four weeks after cessation of treatment, the chylomicron fraction triglyceride AUC had returned to th e pretreatment level, but postprandial chylomicron cholesterol and VLDL cho lesterol, triglyceride, and phospholipid were significantly lower than base line (P < .05). Plasma total cholesterol and LDL cholesterol were significa ntly reduced with treatment (6.2 +/- 0.5 to 4.3 +/- 1.0 mmol/L, P < .001, a nd 4.5 +/- 0.4 to 2.8 +/- 1.0 mmol/L, P < .01, respectively) and returned t o baseline following cessation of treatment. Pasting plasma triglycerides d ecreased significantly on treatment (2.4 +/- 1.0 to 1.7 +/- 0.2 mmol/L, P < .05) but remained significantly lower than baseline 4 weeks later (1.8 +/- 0.3 mmol/L, P < .05). This study suggests major postprandial lipoprotein c hanges on statin therapy which may account, in part, for the beneficial eff ects of statins in the prevention of myocardial infarction. Copyright (C) 2 000 by W.B. Saunders Company.