title: Postprandial apolipoprotein B48-and B100-containing lipoproteins in type 2 diabetes: do statins have a specific effect on triglyceride metabolism?
abstract: There is little information about the effect of an alteration of low-density lipoprotein (LDL) turnover on chylomicron and very-low-density lipoprotein (VLDL) metabolism, yet chylomicron remnant particles are thought to be particularly atherogenic. This study examined the effect of inhibition of cholesterol synthesis on postprandial lipoproteins. Eight type 2 diabetic patients were examined before treatment with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMGCoA) reductase inhibitor cerivastatin, after 4 weeks on active treatment, and 4 weeks after stopping treatment. On each occasion, blood was collected fasting and at 2-hour intervals for up to 8 hours after a high-fat meal. Chylomicrons and VLDLs were isolated by sequential ultracentrifugation. Compositional analysis was performed including the measurement of apolipoprotein 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 from 166 +/- 148 to 70 +/- 70 (P < .05). Postprandial cholesterol (362 +/- 193 to 74 +/- 39, P < .005), triglyceride (2,222 +/- 1,440 to 746 +/- 329), and phospholipid (518 +/- 267 to 205 +/- 94) also decreased (P < .005). In the VLDL fraction, the postprandial cholesterol and triglyceride AUC were significantly 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 the pretreatment level, but postprandial chylomicron cholesterol and VLDL cholesterol, triglyceride, and phospholipid were significantly lower than baseline (P < .05). Plasma total cholesterol and LDL cholesterol were significantly reduced with treatment (6.2 +/- 0.5 to 4.3 +/- 1.0 mmol/L, P < .001, and 4.5 +/- 0.4 to 2.8 +/- 1.0 mmol/L, P < .01, respectively) and returned to baseline following cessation of treatment. Fasting plasma triglycerides decreased 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 changes on statin therapy which may account, in part, for the beneficial effects of statins in the prevention of myocardial infarction.
authors.affiliation: Department of Endocrinology and Diabetes, Adelaide/Mental Hospital, Dublin, Ireland.
authors.forename: S B
authors.initials: SB
authors.lastname: Battula
authors.forename: O
authors.initials: O
authors.lastname: Fitzsimons
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.forename: D
authors.initials: D
authors.lastname: Owens
authors.forename: P
authors.initials: P
authors.lastname: Collins
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: G H
authors.initials: GH
authors.lastname: Tomkin
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011725:Pyridines / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*
chemical_list: D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011725:Pyridines; D014280:Triglycerides; D002784:Cholesterol; C086276:cerivastatin