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論文 |
論文
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Noguchi, Tohru ; Kobayashi, Junji ; Yagi, Kunimasa ; Nohara, Atsushi ; Yamaaki, Naoto ; Sugihara, Masako ; Ito, Naoko ; Oka, Rie ; Kawashiri, Masaaki ; Tada, Hayato ; Takata, Mutsuko ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
概要:
金沢大学医学系研究科<br />Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferato
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r-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. Methods: An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200 mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m2, total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Results: Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p < 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p < 0.001 vs. -32.9%, p < 0.01) and increases in HDL-C (+18.0%, p < 0.001 vs. +11.7%, p < 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p < 0.01; non-HDL-C, -17.3%, p < 0.01; apolipoprotein B, -15.1%, p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p < 0.05) and metabolic markers (γ-GTP, -38.9%, p < 0.01; adiponectin, +15.4%, p < 0.05; urine 8-OHdG/Cre, -9.5%, p < 0.05). Conclusion: Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates. © 2011 Elsevier Ireland Ltd. All rights reserved.
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| 2.
論文 |
論文
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Kobayashi, Junji ; Murase, Yuko ; Asano, Akimichi ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; 小林, 淳二 ; 野原, 淳 ; 川尻, 剛照 ; 稲津, 明広 ; 山岸, 正和 ; 馬渕, 宏
概要:
Objective: To clarify the effects of walking with a pedometer on metabolic parameters, including adiponectin (APN). Meth
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ods: We recruited 44 male Japanese volunteers (age, 37 ± 9 yrs; body mass index (BMI), 24.2 ± 2.9 kg/m2; fasting plasma glucose (FPG), 96 ± 11 mg/dL; total cholesterol (TC) 190 ± 26 mg/dL; triglycerides (TG) 119 ± 80 mg/dL; HDL-C56 ± 14 mg/dL). Subjects were instructed to walk with a pedometer and record the number of steps they walked every day for 50 days. Serum adiponectin (APN) levels were measured by enzyme immunoassay. Treatment effects were examined by Wilcoxon's rank test. Results: The average number of steps was 8211 ± 2084 per day. There were significant reductions in BMI, sBP, TG and TNF-α levels after 50 days, but no changes in adiponectin levels. We then divided the subjects into 2 groups according to the steps walked per day, namely, more than 8000 steps (MT group, n=22) and less than 8000 steps (LT group, n=22) and found that the reduction in TG and BP was observed only in the MT group. Conclusions: Walking with a pedometer is effective for improving metabolic parameters, such as TG and blood pressure, but is not sufficient to increase adiponectin levels in Japanese men.<br />出版者照会後に全文公開
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