title: Statin and fibrate combination does not additionally lower plasma cholesteryl ester transfer in type 2 diabetes mellitus.
abstract: BACKGROUND
  Plasma cholesteryl ester transfer (CET) from high density lipoproteins (HDL) to very low and low density lipoproteins (VLDL+LDL) may predict (subclinical) atherosclerosis. We tested the extent to which plasma CET and cholesterol esterification (EST) are decreased by statin and fibrate combination therapy compared to statin and fibrate administration alone in type 2 diabetic patients.
  
  
  METHODS
  Plasma CET and EST were measured by isotope assays in 14 type 2 diabetic patients, in whom a randomized placebo-controlled crossover study was carried out (8 weeks treatment with simvastatin (40 mg daily), bezafibrate (400 mg daily) and their combination). Plasma CET and EST from diabetic patients were compared with 42 non-diabetic control subjects with similar triglyceride levels.
  
  
  RESULTS
  Plasma CET and EST were elevated in diabetic patients at baseline compared to control subjects (p < 0.01), and were correlated positively with non-HDL cholesterol and triglycerides in non-diabetic subjects and in diabetic patients at baseline (p < 0.01). Decreases in CET during combined treatment (p < 0.05) were not greater than the changes during simvastatin and bezafibrate monotherapy (p > 0.20). EST only decreased during bezafibrate therapy (p < 0.05). Changes in CET during treatment were correlated positively with changes in non-HDL cholesterol (p < 0.05) and triglycerides (p < 0.001). Changes in HDL cholesterol were related inversely to changes in CET (p < 0.05).
  
  
  CONCLUSIONS
  Diabetes-associated plasma CET elevations are ameliorated by statin and fibrate monotherapy, but combined lipid lowering drug treatment does not additively lower CET. CET lowering likely contributes to HDL cholesterol changes during statin and fibrate administration.
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, The Netherlands. r.p.f.dullaart@int.umcg.nl
authors.forename: Rindert
authors.initials: R
authors.lastname: de Vries
authors.forename: Bert D
authors.initials: BD
authors.lastname: Dikkeschei
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Arie
authors.initials: A
authors.lastname: van Tol
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D001629:Bezafibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D019821:Simvastatin; D001629:Bezafibrate