title: High-dose statin therapy does not induce insulin resistance in patients with familial hypercholesterolemia.
abstract: BACKGROUND
  Insulin resistance is thought to play a pathophysiological role in the development of atherosclerosis. Decreased adiponectin levels are associated with hyperinsulinemia, insulin resistance, and coronary artery disease. Patients with familial hypercholesterolemia (FH) develop premature atherosclerosis and should be insulin resistant and have low adiponectin levels.
  
  
  METHODS
  A total of 51 homozygous FH (HoFH) and 20 heterozygous FH (HeFH) patients were studied before and after statin therapy. Twenty normocholesterolemic subjects were controls. Fasting lipograms, glucose, insulin, proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP) were measured. Insulin resistance was calculated with the homeostasis model assessment (HOMA-IR) formula. Carotid intima media thickness (CIMT) was measured as a subclinical marker of atherosclerosis.
  
  
  RESULTS
  On multiple regression analysis, the major determinant of insulin resistance measured by HOMA-IR was body mass index (BMI) (r=0.54; P=0.004). On simple linear regression, the highest correlation was with BMI (r=0.39; P=0.0002). Log hsCRP correlated with BMI (r=0.35; P<0.002) and insulin resistance (r=0.22; P=0.05). Low-density lipoprotein cholesterol (LDL-C) and CIMT did not correlate with insulin resistance. Unexpectedly, adiponectin levels were highest in HoFH patients and correlated with LDL-C (r=0.34; P=0.001). No change in the degree of IR was observed with statin therapy.
  
  
  CONCLUSIONS
  FH patients are not insulin resistant and do not have low adiponectin levels. There was no significant change in insulin resistance with high-dose statin therapy.
authors: Carbohydrate & Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors: Vanessa
authors: V
authors: Panz
authors: Andrew
authors: A
authors: Immelman
authors: Janice
authors: J
authors: Paiker
authors: Gillian
authors: G
authors: Pilcher
authors: Frederick
authors: F
authors: Raal
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D059168:Carotid Intima-Media Thickness; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids