title: Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment.
abstract: OBJECTIVE
  Cellular cholesterol efflux to plasma is important in reverse cholesterol transport and may be affected by simvastatin in type 1 diabetes mellitus.
  
  
  METHODS
  In 14 moderately hypercholesterolaemic type 1 diabetic and 13 healthy men we determined plasma (apo)lipoproteins, pre-beta HDL formation, cholesteryl ester transfer protein (CETP) activity, phospholipid transfer protein (PLTP) activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux out of Fu5AH cells and fibroblasts. After diet run-in, diabetic patients were randomly treated with simvastatin 10, 20, 40 mg and placebo, once daily each, for 6 weeks in a double-blind crossover design.
  
  
  RESULTS
  Plasma very low density lipid protein (VLDL)+LDL cholesterol, LDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, apo B, CETP activity, PLTP activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux from Fu5AH cells and fibroblasts were higher in diabetic patients. Pre-beta HDL formation was unaltered. Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol, triglycerides and apo B, CETP activity, cholesterol esterification and cholesteryl ester transfer. HDL cholesterol increased and its change was correlated with the change in cholesteryl ester transfer. The ability to promote cholesterol efflux from Fu5AH cells and fibroblasts did not change after simvastatin.
  
  
  CONCLUSIONS
  The capacity of plasma from moderately hypercholesterolaemic type 1 diabetic patients to induce cholesterol efflux out of Fu5AH cells and fibroblasts is enhanced, probably due to higher apo A-I, HDL phospholipids and PLTP activity. Simvastatin increases HDL cholesterol in type 1 diabetic patients via lowering of plasma cholesteryl ester transfer. The HDL changes after simvastatin do not increase cellular cholesterol efflux further.
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, Groningen, 9700, The Netherlands. r.de.vries@int.umcg.nl
authors.forename: R
authors.initials: R
authors.lastname: de Vries
authors.forename: M N
authors.initials: MN
authors.lastname: Kerstens
authors.forename: W J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: A K
authors.initials: AK
authors.lastname: Groen
authors.forename: A
authors.initials: A
authors.lastname: van Tol
authors.forename: R P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004311:Double-Blind Method; D005347:Fibroblasts / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D012016:Reference Values; D019821:Simvastatin / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D019821:Simvastatin; D014280:Triglycerides