Abstract 3516: Simvastatin Reduces Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients Regardless of Doses
Background: Lipophilic statins particularly high dose may cause unfavorable pleiotropic effects such as exacerbation of insulin resistance. Indeed, simvastatin either did not change or worsened insulin sensitivity in patients. We investigated metabolic responses to different doses of simvastatin in hypercholesterolemic patients.
Methods: This was a randomized, double-blind, placebo-controlled, and parrelled study. Age, sex, and body mass index were matched. All patients were recommended low fat diet. Thirty-two patients were given placebo and 30, 32, 31, and 31 patients were given simvastatin 10, 20, 40, and 80 mg, respectively once during 2 month treatment period.
Results: When baseline values before each treatment period were compared among each treatment arm, no significant differences were noted in any of the parameters measured. Placebo significantly reduced total cholesterol and LDL cholesterol levels, however, did not significantly decrease plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. Simvastatin 10, 20, 40, and 80 mg significantly reduced total cholesterol (mean % changes; by 27%, 25%, 37%, and 38%), LDL cholesterol (by 39%, 38%, 52%, and 54%) and apolipoprotein B levels (24%, 30%, 36%, and 42%) after 2 months administration relative to baseline measurements (all P<0.001 by paired t-test). And these effects of four different doses of simvastatins were significant compared with placebo (all P<0.001 by ANOVA). Simvastatin 10, 20, 40, and 80 mg significantly decreased plasma adiponectin levels (by 4%, 12%, 5%, and 10%) and insulin sensitivity (5%, 8%, 6%, and 6%) relative to baseline measurements (all P<0.05 by paired t-test). And these effects of four different doses of simvastatins were significant compared with placebo (P=0.011 for adiponectin and P=0.034 for QUICKI by ANOVA). However, the magnitude of these changes (adiponectin and QUICKI) were not significantly different among four different doses of simvastatin therapies despite of different extents of LDL cholesterol reduction.
Conclusions: Simvastatin reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients regardless of doses.