Effects of simvastatin on fasting and postprandial triglyceride-rich lipoproteins in patients with type I diabetes mellitus.
To assess the effect of simvastatin on fasting and postprandial triglyceride (TG)-rich lipoproteins in subjects with type 1 diabetes and elevated LDL cholesterol levels, eight patients participated in a simvastatin versus placebo, randomized, crossover study. At the end of each drug period fasting and postprandial lipoprotein studies were undertaken. Fasting plasma total and LDL cholesterol and apolipoprotein B (apo B) were significantly lower on simvastatin compared to placebo. Postprandial studies: simvastatin versus placebo consistently decreased the area under the curve (AUC, mean+/-SEM) of TG in plasma (12.52+/-9.07 versus 18.70+/-10.48 mmol x h/L, p = 0.02). Similarly, TG AUC was lower: in the chylomicron subfraction (Sf > 400) 3.24+/-2.71 versus 5.27+/-4.61 mmol x h/L p = 0.03; and in the [chylomicron remnant + VLDL] subfraction (Sf 20-400) 3.98+/-2.51 versus 7.04+/-3.88 mmol x h/L, p = 0.01. This was due to decreased particle n umber rather than size, as shown by a decrease in the AUC of apo B in Sf 20-400 (600+/-360 versus 980+/-600 mg x h/L, p = 0.02) and the lack of change in the ratio of TG/apo B. Intestinal lipoproteins contributed to the simvastatin effect, as shown by the lower AUC of retinyl esters in both subfractions. Chylomicrons: 627.61+/-363.43 versus 948.19+/-568.34 nmol x h/L, p = 0.02 and remnants: 129.23+/-67.12 versus 208.49+/-92.11 nmol x h/L, p = 0.04. Our data suggest an additional mechanism by which simvastatin can decrease the risk of atherosclerosis in patients with type I diabetes: a decrease of the number of circulating intestinal and hepatic postprandial TG-rich lipoprotein particles.
Noutsou
M
M
Minneapolis Veterans Affairs Medical Center, Minnesota, 55417, USA.
Georgopoulos
A
A
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005215:Fasting; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007118:Immunoassay; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019821:Simvastatin / Q000494:pharmacology*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002914:Chylomicrons; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin