A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) exerts beneficial effects on the cardiovascular system. Here, we examined the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on systemic inflammation and pro-inflammatory (M1)/anti-inflammatory (M2)-like phenotypes of peripheral blood monocytes in diabetic patients.


METHODS
Forty-eight type 2 diabetic patients were divided into the following two groups: sitagliptin-treatment (50mg daily for 3months) (n=24) and untreated control (n=24) groups. Measurements were undertaken to assess changes in glucose-lipid metabolism, serum levels of inflammatory cytokines such as serum amyloid A-LDL (SAA-LDL), C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α). Furthermore, the effects of sitagliptin treatment on M1/M2-like phenotypes in peripheral blood monocytes were examined.


RESULTS
Treatment with sitagliptin significantly decreased fasting plasma glucose, hemoglobin A1c (HbA1c), serum levels of inflammatory markers, such as SAA-LDL, CRP, and TNF-α. In contrast, sitagliptin increased serum IL-10, an anti-inflammatory cytokine, as well as plasma GLP-1. In addition, sitagliptin increased monocyte IL-10 expression and decreased monocyte TNF-α expression. Multivariate regression analysis revealed that the sitagliptin treatment was the only factor independently associated with an increase in monocyte IL-10 (β=0.499; R(2)=0.293, P<0.05). However, other factors including the improvement of glucose metabolism were not associated with the increase.


CONCLUSIONS
This study is the first to show that a DPP-4 inhibitor, sitagliptin, reduces inflammatory cytokines and improves the unfavorable M1/M2-like phenotypes of peripheral blood monocytes in Japanese type 2 diabetic patients.
Division of Diabetic Research, Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan. norikos@oregano.ocn.ne.jp
Noriko
N
Satoh-Asahara
Yousuke
Y
Sasaki
Hiromichi
H
Wada
Mayu
M
Tochiya
Azusa
A
Iguchi
Reiko
R
Nakagawachi
Shinji
S
Odori
Shigeo
S
Kono
Koji
K
Hasegawa
Akira
A
Shimatsu
D001786:Blood Glucose / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology; D002784:Cholesterol / Q000097:blood / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage*; D012044:Regression Analysis; D000685:Serum Amyloid A Protein / Q000276:immunology; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015850:Interleukin-6; D011719:Pyrazines; D000685:Serum Amyloid A Protein; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052216:Glucagon-Like Peptide 1; D002097:C-Reactive Protein; D002784:Cholesterol; D000068900:Sitagliptin Phosphate