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Satoh-Asahara N.,Clinical Research Institute for Endocrine Metabolic Diseases | Sasaki Y.,Clinical Research Institute for Endocrine Metabolic Diseases | Wada H.,Clinical Research Institute | Tochiya M.,Diabetes Center | And 8 more authors.
Metabolism: Clinical and Experimental | Year: 2013

Aims/hypothesis: 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 (50 mg daily for 3 months) (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; R2 = 0.293, P < 0.05). However, other factors including the improvement of glucose metabolism were not associated with the increase. Conclusions/interpretation: 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. © 2013 Elsevier Inc.


Yamakage H.,Clinical Research Institute for Endocrine Metabolic Diseases | Muranaka K.,Clinical Research Institute for Endocrine Metabolic Diseases | Tanaka M.,Clinical Research Institute for Endocrine Metabolic Diseases | Matsuo Y.,Clinical Research Institute for Endocrine Metabolic Diseases | And 8 more authors.
Endocrine Journal | Year: 2014

An increase in intra-abdominal fat area (IAFA) is an essential component of metabolic syndrome (MetS). Waist circumference (WC) is not a precise measure of IAFA, and computed tomography (CT) is unsuitable for frequent monitoring. Here, we examined utility of a dual bioelectrical impedance analysis (Dual BIA) for measuring IAFA in obese patients during weight reduction. Fat distribution was measured by Dual BIA and CT in 100 obese outpatients. All fat areas including total, IAFA, and subcutaneous fat by Dual BIA were more closely correlated with those by CT than WC. Estimated IAFA by Dual BIA was significantly correlated with number of MetS components as well as CT, but WC was not. Furthermore, in 61 obese patients who received 6-month weight reduction therapy, estimated IAFA by Dual BIA showed an earlier and greater decrease as well as that by CT than WC and BMI. In addition, decrease in estimated IAFA by Dual BIA through weight reduction had a higher correlation with decrease in IAFA by CT, than WC. This study is the first to demonstrate that the change in estimated IAFA by Dual BIA was highly correlated with that in IAFA by CT during weight reduction therapy. Our findings also indicate that estimated IAFA by Dual BIA is, potentially, a better indicator of severity of MetS, cardiovascular risk factors, and effectiveness of weight reduction than WC, and equal to IAFA by CT. Estimated IAFA by Dual BIA may be useful for monitoring the effectiveness of weight reduction therapy in obese patients. © The Japan Endocrine Society.

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