Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

• Published in: Metabolism, clinical and experimental Vol. 63; no. 9; pp. 1141 - 1148
• Main Authors: Tremblay, André J., Lamarche, Benoît, Deacon, Carolyn F., Weisnagel, S. John, Couture, Patrick
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2014; Elsevier
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Biomarkers - blood; Biomarkers - chemistry; Cell Adhesion Molecules - blood; Cell Adhesion Molecules - chemistry; Cross-Over Studies; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Dipeptidyl peptidase-4; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Double-Blind Method; Down-Regulation - drug effects; E-Selectin - blood; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptide 1 - blood; Humans; Inflammation; Inflammation Mediators - blood; Intercellular Adhesion Molecule-1 - blood; Intercellular Adhesion Molecule-1 - chemistry; Male; Medical sciences; Middle Aged; Phospholipases A2, Secretory - blood; Phospholipases A2, Secretory - metabolism; Pyrazines - therapeutic use; Sitagliptin; Sitagliptin Phosphate; Solubility; Triazoles - therapeutic use; Type 2 diabetes; Vertebrates: anatomy and physiology, studies on body, several organs or systems; CRP; FFA; Type 2 diabetes; Apo; GLP-1; IL-1; DPP-4; Sitagliptin; ICAM-1; Inflammation; IL-6; GIP; HDL; VCAM-1; TG; TNF-α; LDL; IL-18; VLDL; PAI-1; HOMA; sPLA2; Dipeptidyl peptidase-4; triglyceride; apolipoprotein; low density lipoprotein; C-reactive protein; interleukin-1; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; interleukin-6; vascular cell adhesion molecule-1; soluble intercellular adhesion molecule-1; secreted phospholipase-A 2; dipeptidyl peptidase-4; homeostatic model assessment; plasminogen activator inhibitor-1; interleukin-18; free fatty acid; tumor necrosis factor-α; very low density lipoprotein; high density lipoprotein; Dipeptidyl-peptidase IV; Endocrinopathy; Human; Enzyme; Cell adhesion molecule; Enzyme inhibitor; Metabolic diseases; Marker; Peptidases; Hypoglycemic agent; Treatment; Gliptine derivatives; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Endocrinology
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2014.06.004

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. 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. Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1±6.4years and a body mass index of 30.7±4.9kg/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. Treatment with sitagliptin for 6weeks 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.