Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes
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 diabete...
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| Published in | Metabolism, clinical and experimental Vol. 63; no. 9; pp. 1141 - 1148 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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New York, NY
Elsevier Inc
01.09.2014
Elsevier |
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| 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.
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. |
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| AbstractList | 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 ± 6.4 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.
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. 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. 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.UNLABELLEDInflammation 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.OBJECTIVEThe 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 ± 6.4 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.METHODS AND RESULTSThirty-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.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.CONCLUSIONSTreatment 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. 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. Methods and 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 (100 mg/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. |
| Author | Lamarche, Benoît Deacon, Carolyn F. Weisnagel, S. John Tremblay, André J. Couture, Patrick |
| Author_xml | – sequence: 1 givenname: André J. surname: Tremblay fullname: Tremblay, André J. organization: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada – sequence: 2 givenname: Benoît orcidid: 0000-0002-4443-5378 surname: Lamarche fullname: Lamarche, Benoît organization: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada – sequence: 3 givenname: Carolyn F. surname: Deacon fullname: Deacon, Carolyn F. organization: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark – sequence: 4 givenname: S. John surname: Weisnagel fullname: Weisnagel, S. John organization: Diabetes Research Unit, CHUL Research Centre, Quebec City, Quebec, Canada – sequence: 5 givenname: Patrick surname: Couture fullname: Couture, Patrick email: patrick.couture@crchul.ulaval.ca organization: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28765856$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/25034387$$D View this record in MEDLINE/PubMed |
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| Keywords | 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 |
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| SubjectTerms | 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 |
| Title | Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes |
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