Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study

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• 作者：Tohru Noguchi^a ; Junji Kobayashi^a ; ^{junji@med.kanazawa-u.ac.jp"" rel=""nofollow} ; Kunimasa Yagi^b ; Atsushi Nohara^a ; Naoto Yamaaki^b ; Masako Sugihara^b ; Naoko Ito^b ; Rie Oka^c ; Masa-aki Kawashiri^b ; Hayato Tada^b ; Mutsuko Takata^b ; Akihiro Inazu^d ; Masakazu Yamagishi^b ; Hiroshi Mabuchi^a
• 关键词：PCSK9 ; Bezafibrate ; Fenofibrate ; Diabetes ; Dyslipidemia ; Peroxisome proliferator-activated receptor (PPAR) ; Adiponectin
• 刊名：Atherosclerosis
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：217
• 期：1
• 页码：165-170
• 全文大小：165 K

文摘

Background

Bezafibrate and fenofibrate show different binding properties against peroxisome proliferator-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 (&#x2212;38.3 % , p < 0.001 vs. &#x2212;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, &#x2212;11.2 % , p < 0.01; non-HDL-C, &#x2212;17.3 % , p < 0.01; apolipoprotein B, &#x2212;15.1 % , p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, &#x2212;17.0 % , p < 0.05) and metabolic markers (γ-GTP, &#x2212;38.9 % , p < 0.01; adiponectin, +15.4 % , p < 0.05; urine 8-OHdG/Cre, &#x2212;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.