title: Bezafibrate improves insulin resistance evaluated using the glucose clamp technique in patients with type 2 diabetes mellitus: a small-scale clinical study.
abstract: BACKGROUND
  Bezafibrate is mainly used to treat hypertriglyceridemia. Studies have reported that bezafibrate also improves type 2 diabetes mellitus, but the mechanism has not been fully elucidated. We performed euglycemic hyperinsulinemic clamps (glucose clamp) and meal tolerance tests (MTT) to examine the effects of bezafibrate on insulin resistance in patients with type 2 diabetes mellitus.
  
  
  METHODS
  Twelve Japanese patients with type 2 diabetes mellitus and dyslipidemia (mean age: 59.5 years; fasting plasma glucose: 7.95 mmol/L; hemoglobin A1c [HbA1c]: 7.3%; body mass index: 26.5 kg/m(2)) underwent a glucose clamp and MTT before and after 12 weeks of treatment with 400 mg/day bezafibrate. The glucose infusion rate was measured during the glucose clamp. The patients took a test meal (460 kcal) in the MTT. Plasma glucose and immunoreactive insulin levels were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum C-peptide immunoreactivity, serum lipids, and liver function markers were also measured during the MTT.
  
  
  RESULTS
  Bezafibrate significantly increased the mean glucose infusion rate from 5.78 ± 1.94 to 6.78 ± 2.52 mg/kg/min (p < 0.05). HbA1c improved from 7.30 ± 0.55% to 7.02 ± 0.52% (p < 0.05). In the MTT, fasting plasma glucose decreased from 7.95 ± 1.15 to 6.98 ± 1.07 mmol/L (p < 0.05). The area under the plasma glucose curve from 0 to 180 min decreased significantly from 29.48 ± 5.07 to 27.12 ± 3.98 mmol/h/L (p < 0.05), whereas immunoreactive insulin was unchanged. Furthermore, bezafibrate also significantly improved serum lipids, with decreases in triglyceride levels from 1.84 ± 0.88 to 1.14 ± 0.41 mmol/L (p < 0.05), low-density lipoprotein cholesterol levels from 3.56 ± 0.83 to 2.92 ± 0.55 mmol/L (p < 0.05), and remnant-like particle cholesterol levels decreased from 0.25 ± 0.16 to 0.14 ± 0.06 mmol/L (p < 0.05), and increases in high-density lipoprotein cholesterol levels from 1.50 ± 0.24 to 1.66 ± 0.29 mmol/L (p < 0.05).
  
  
  CONCLUSIONS
  Bezafibrate improved glucose intolerance and peripheral insulin resistance in these Japanese patients with type 2 diabetes mellitus and dyslipidemia. Therefore, bezafibrate could be used to treat insulin resistance in patients with type 2 diabetes mellitus and dyslipidemia.
  
  
  BACKGROUND
  University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000012462.
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiochi
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohkura
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sumi
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Nakanishi
authors.affiliation: Department of Regional Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504 Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuzawa
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Schoichiro
authors.initials: S
authors.lastname: Izawa
authors.affiliation: Department of Regional Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504 Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohkura
authors.affiliation: Department of Regional Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504 Japan.
authors.forename: Kazuoki
authors.initials: K
authors.lastname: Inoue
authors.affiliation: School of Health Science, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504 Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ueta
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Regional Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504 Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Nishi-chou 36-1, Yonago, Tottori, 683-8504 Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
keywords: Bezafibrate; Glucose clamp; Insulin resistance; Japanese patients; Meal tolerance test; Type 2 diabetes mellitus