title: Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus.
abstract: BACKGROUND
  High density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.
  
  
  METHODS
  HDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0±1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).
  
  
  RESULTS
  HOMA-β was lowest, whereas HOMAir was highest in T2DM (P<0.01 and P<0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P<0.05) and cellular cholesterol efflux (P<0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P=0.001) and cellular cholesterol efflux (P=0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.
  
  
  CONCLUSIONS
  Pancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.
authors.affiliation: Department of Endocrinology, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: Wijtske
authors.initials: W
authors.lastname: Annema
authors.forename: Jan Freark
authors.initials: JF
authors.lastname: de Boer
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010084:Oxidation-Reduction
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008075:Lipoproteins, HDL; C517652:hemoglobin A1c protein, human