title: Basal and insulin-regulated VLDL1 and VLDL2 kinetics in men with type 2 diabetes.
abstract: OBJECTIVE
  Hypertriacylglycerolaemia is a hallmark of diabetic dyslipidaemia with increased concentrations of triacylglycerol (TG)-rich VLDL1 particles. However, whether VLDL1 secretion or removal is abnormal in type 2 diabetes remains unclear. The aim of this study was to compare basal and insulin-mediated VLDL1- and VLDL2-TG kinetics in men with type 2 diabetes and healthy men using a novel direct VLDL1- and VLDL2-TG labelling method.
  
  
  METHODS
  Twelve men with type 2 diabetes and 12 healthy men matched for age and BMI were recruited. VLDL1- and VLDL2-TG turnover were measured during a 4 h basal period and a 3.5 h hyperinsulinaemic clamp period using a primed-constant infusion of ex vivo labelled VLDL1-TG and VLDL2-TG.
  
  
  RESULTS
  Basal VLDL1-TG and VLDL2-TG secretion rates were similar in men with diabetes and healthy men. During hyperinsulinaemia, VLDL1-TG secretion rates were suppressed significantly in both groups, whereas no suppression of VLDL2-TG secretion rate was observed. VLDL1-TG to VLDL2-TG transfer rate was not significantly different from zero in both groups, while VLDL1-TG fatty acid oxidation rate was substantial, with a contribution to total energy expenditure of approximately 15% during postabsorptive conditions. VLDL1 and VLDL2 particle size (TG/apolipoprotein B [apoB] ratio) and apoB-100 concentration were unaltered by hyperinsulinaemia in men with type 2 diabetes, but significantly reduced in healthy men.
  
  
  CONCLUSIONS
  Insulin inhibits VLDL1-TG secretion rate similarly in age- and BMI-matched men with type 2 diabetes and healthy men, while VLDL2-TG secretion is unaltered by hyperinsulinaemia. However, VLDL1- and VLDL2-apoB levels are not lowered by hyperinsulinaemia in men with type 2 diabetes, which is indicative of a diminished hepatic response to insulin.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01564550.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark. rfjohansen@clin.au.dk.
authors.forename: Rakel F
authors.initials: RF
authors.lastname: Johansen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.|The Danish Diabetes Academy, Odense, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Søndergaard
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Sørensen
authors.affiliation: Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne Grethe
authors.initials: AG
authors.lastname: Jurik
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007328:Insulin; D007333:Insulin Resistance; D007700:Kinetics; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D007328:Insulin; D008079:Lipoproteins, VLDL
keywords: Dyslipidaemia; Healthy men; Hyperinsulinaemic clamp; Insulin resistance; Kinetics; Type 2 diabetes; VLDL1; VLDL2