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 × h/L, p = 0.02). Similarly, TG AUC was lower: in the chylomicron subfraction (S_f > 400) 3.24 ± 2.71 versus 5.27 ± 4.61 mmol × h/L p = 0.03; and in the chylomicron remnant + VLDL] subfraction (S_f 20–400) 3.98 ± 2.51 versus 7.04 ± 3.88 mmol × h/L, p = 0.01. This was due to decreased particle number rather than size, as shown by a decrease in the AUC of apo B in S_f 20–400 (600 ± 360 versus 980 ± 600 mg × 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 × h/L, p = 0.02 and remnants: 129.23 ± 67.12 versus 208.49 ± 92.11 nmol × 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.