title: Simvastatin and bezafibrate increase cholesterol efflux in men with type 2 diabetes.
abstract: BACKGROUND
  The importance of functional properties of high-density lipoproteins (HDL) for atheroprotection is increasingly recognized. We determined the impact of lipid-lowering therapy on 3 key HDL functionalities in Type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  A placebo-controlled, randomized cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), alone and in combination) was carried out in 14 men with T2DM. Cholesterol efflux was determined using human THP-1 monocyte-derived macrophages, HDL antioxidative capacity was measured as inhibition of low-density lipoprotein oxidation in vitro, and HDL anti-inflammatory capacity was assessed as suppression of thrombin-induced monocyte chemotactic protein 1 expression in human umbilical vein endothelial cells. Pre-β-HDL was assayed using crossed immunoelectrophoresis.
  
  
  RESULTS
  While cholesterol efflux increased in response to simvastatin, bezafibrate and combination treatment (+12 to +23%; anova, P = 0.001), HDL antioxidative capacity (P = 0.23) and HDL anti-inflammatory capacity (P = 0.15) did not change significantly. Averaged changes in cellular cholesterol efflux during active treatment were correlated positively with changes in HDL cholesterol, apoA-I and pre-β-HDL (P < 0.05 to P < 0.001). There were no inter-relationships between changes in the three HDL functionalities during treatment (P > 0.10). Changes in HDL antioxidative capacity and anti-inflammatory capacity were also unrelated to changes in HDL cholesterol and apoA-I, while changes in HDL antioxidative capacity were related inversely to pre-β-HDL (P < 0.05).
  
  
  CONCLUSIONS
  Simvastatin and bezafibrate increase cholesterol efflux, parallel to HDL cholesterol and apoA-I responses. The antioxidative and anti-inflammatory properties of HDL are not to an important extent affected by these therapeutic interventions.
authors: Department of Endocrinology, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Michela
authors: M
authors: Triolo
authors: Wijtske
authors: W
authors: Annema
authors: Jan Freark
authors: JF
authors: de Boer
authors: Uwe J F
authors: UJ
authors: Tietge
authors: Robin P F
authors: RP
authors: Dullaart
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001629:Bezafibrate / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D053442:High-Density Lipoproteins, Pre-beta / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D019821:Simvastatin; D001629:Bezafibrate
keywords: HDL anti-inflammatory capacity; HDL antioxidative capacity; Type 2 diabetes mellitus; cholesterol efflux; fibrate; statin