title: Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes.
abstract: Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized.
  
  
  OBJECTIVE
  The objective of the present study was to examine the effects of treatment with sitagliptin on the plasma levels of various markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes.
  
  
  RESULTS
  Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m²) were recruited into this double-blind, cross-over study using sitagliptin (100mg/d) or placebo, each for a 6-week period, including a 4-week washout period between the two phases. Blood samples were taken at the end of each phase of treatment. Compared with placebo, treatment with sitagliptin significantly reduced the plasma levels of C-reactive protein (CRP) (44.9%, P=0.006), interleukin (IL)-6 (24.7%, P=0.04), IL-18 (7.3%, P=0.004), secreted phospholipase-A₂ (sPLA₂) (12.9%, P=0.04), soluble intercellular adhesion molecule-1 (5.3%, P=0.002), and E-selectin (5.9%, P=0.005). A significant inverse correlation was found between changes in glucagon-like peptide-1 (GLP-1) and changes in CRP levels (r=0.41, P=0.01) following sitagliptin therapy. Sitagliptin therapy had more pronounced effects in subjects with higher levels of inflammatory markers and cell adhesion molecules compared with subjects with lower levels.
  
  
  CONCLUSIONS
  Treatment with sitagliptin for 6 weeks reduced plasma markers of low-grade inflammation and cell adhesion molecules, most likely by increasing plasma GLP-1 levels and improving glucose-insulin homeostasis. These beneficial effects of sitagliptin might represent a further advantage in the management of diabetes and its proatherogenic comorbidities.
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada; Lipid Research Centre, CHUL Research Centre, Quebec City, Quebec, Canada.
authors.forename: André J
authors.initials: AJ
authors.lastname: Tremblay
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.affiliation: Diabetes Research Unit, CHUL Research Centre, Quebec City, Quebec, Canada.
authors.forename: S John
authors.initials: SJ
authors.lastname: Weisnagel
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada; Lipid Research Centre, CHUL Research Centre, Quebec City, Quebec, Canada. Electronic address: patrick.couture@crchul.ulaval.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000737:chemistry; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000097:blood / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D012995:Solubility; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D054873:Dipeptidyl-Peptidase IV Inhibitors; D019040:E-Selectin; C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D011719:Pyrazines; C546936:SELE protein, human; D014230:Triazoles; D018799:Intercellular Adhesion Molecule-1; D052216:Glucagon-Like Peptide 1; D054497:Phospholipases A2, Secretory; D000068900:Sitagliptin Phosphate
keywords: Dipeptidyl peptidase-4; Inflammation; Sitagliptin; Type 2 diabetes