title: Rosuvastatin dose-dependently improves flow-mediated dilation, but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients.
abstract: BACKGROUND
  Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients.
  
  
  METHODS
  A randomized, single-blind, placebo-controlled, parallel study was conducted in 48 patients on placebo, and in 47, 48, and 47 patients given daily rosuvastatin 5, 10, and 20mg, respectively during a 2month treatment period.
  
  
  RESULTS
  Rosuvastatin 5, 10, and 20mg improved flow-mediated dilation (34, 40, and 46%) after 2months therapy when compared with baseline (P<0.001 by paired t-test) and when compared with placebo (P<0.001 by ANOVA). Rosuvastatin 5,10, and 20mg dose-dependently and significantly increased insulin (mean % changes; 19, 29, and 31%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2months therapy when compared with baseline (all P<0.05 by paired t-test). These effects with rosuvastatin 5, 10, and 20mg were significant when compared with placebo (P=0.006 for insulin, P=0.012 for glycated hemoglobin, P=0.007 for adiponectin, and P=0.002 for insulin sensitivity by ANOVA).
  
  
  CONCLUSIONS
  Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea. Electronic address: kwangk@gilhospital.com.
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Pyung Chun
authors.initials: PC
authors.lastname: Oh
authors.affiliation: Cardiovascular Medicine, Hokko Memorial Clinic, Sapporo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.affiliation: Department of Statistics, University of Seoul, Seoul, Republic of Korea.
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D052242:Adiponectin / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D016037:Single-Blind Method; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D000068718:Rosuvastatin Calcium
keywords: Adipocytokines; Glycated hemoglobin; Insulin resistance; Metabolic syndrome; Statins