title: Effect of sitagliptin therapy on triglyceride-rich lipoprotein kinetics in patients with type 2 diabetes.
abstract: OBJECTIVE
  To investigate the effects of sitagliptin therapy on the kinetics of triglyceride-rich lipoprotein (TRL) apolipoprotein (apo)B-48, VLDL apoB-100, apoE and apoC-III in patients with type 2 diabetes.
  
  
  METHODS
  Twenty-two subjects with type 2 diabetes were recruited in this double-blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6-week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed-constant infusion of l-[5,5,5-D3]leucine for 12 h, with the participants in a constantly fed state.
  
  
  RESULTS
  Sitagliptin therapy significantly reduced fasting plasma triglyceride (-15.4%, p = 0.03), apoB-48 (-16.3%, p = 0.03) and free fatty acid concentrations (-9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (-13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB-48 by -20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (-16.0%, p = 0.03). The VLDL apoB-100 pool size was also significantly decreased by sitagliptin therapy (-9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance (-9.2%, p = 0.06).
  
  
  CONCLUSIONS
  Treatment with sitagliptin for 6 weeks reduced triglyceride-rich apoB-containing lipoprotein levels by reducing the synthesis of these particles.
authors: Lipid Research Centre, Centre Hospitalier de l'Université Laval (CHUL) Research Centre, Quebec City, QC, Canada; Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC, Canada.
authors: A J
authors: AJ
authors: Tremblay
authors: B
authors: B
authors: Lamarche
authors: I
authors: I
authors: Kelly
authors: A
authors: A
authors: Charest
authors: M-C
authors: MC
authors: Lépine
authors: A
authors: A
authors: Droit
authors: P
authors: P
authors: Couture
mesh_terms: D053283:Apolipoprotein B-48 / Q000097:blood / Q000187:drug effects; D001053:Apolipoproteins / Q000097:blood / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D053283:Apolipoprotein B-48; D001053:Apolipoproteins; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014280:Triglycerides; C517652:hemoglobin A1c protein, human
keywords: apolipoprotein B-100; apolipoprotein B-48; dipeptidyl peptidase-4; glucagon-like peptide-1; glucose; insulin; kinetic; sitagliptin; type 2 diabetes