title: Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.
abstract: Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied. We here investigated the cholesterol efflux capacity of HDL from IF and plasma from T2D patients and healthy controls.
  
  
  
  HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age- and sex-matched healthy controls. Cholesterol efflux to HDL was determined in vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages. Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy controls, in line with previous observations. This difference was much more pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D. Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of plasma HDL, by 15% and 32% in controls and T2D patients, respectively.
  
  
  
  These data demonstrate that (1) HDL from IF has a lower cholesterol efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is severely impaired in T2D when compared with controls. Because IF comprises the compartment where reverse cholesterol transport is initiated, the marked reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an important role for their increased risk to develop atherosclerosis.
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.). johanna.apro@ki.se.
authors.forename: Johanna
authors.initials: J
authors.lastname: Apro
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.).
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.).
authors.forename: Arne
authors.initials: A
authors.lastname: Dikkers
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.).
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
authors.affiliation: From the Metabolism Unit (J.A., P.P., B.A., M.R.) and KI/AZ Integrated CardioMetabolic Center (J.A., B.A., M.R.), Department of Medicine and Department of Biosciences and Nutrition (J.A., B.A., M.R.), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. Department of Pediatrics, The University of Groningen, University Medical Center Groningen, Groningen, The Netherlands (U.J.F.T., A.D.); and Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden (P.P.).
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
mesh_terms: D001692:Biological Transport; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D013997:Time Factors
chemical_list: D008076:Cholesterol, HDL
keywords: diabetes mellitus, type 2; extracellular fluid; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; macrophages