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Three-month treatment with pioglitazone reduces circulating levels of thiobarbituric acid-reacting substances, a marker of reactive oxidative stress, without change in body mass index, in Japanese patients with type 2 diabetes

  • Hideaki Nakatsuji
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka 565-0871, Japan
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  • Ken Kishida
    Correspondence
    Corresponding author. Tel.: +81 6 6879 3732; fax: +81 6 6879 3739.
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka 565-0871, Japan
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  • Tohru Funahashi
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka 565-0871, Japan
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  • Iichiro Shimomura
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka 565-0871, Japan
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  • The Senri Study II Group
    Author Footnotes
    1 The following are members of The Senri Study II Group: Drs. Hideki Asakawa, Toshio Amano, Akira Amenomori, Naoto Itoh, Yasuko Kusaka, Kouhei Kuroda, Kouken Boku, Suguru Sato, Mamiko Tsugawa, Seiichi Sumi, Naoji Takeuchi, Makoto Nakao, Keizo Noma, Atsushi Hirotani, Katsuto Shirouzu, Kosuke Nitta, Mitsuo Midorikawa, Koji Yokokawa and Hiroaki Yoshioka.
  • Author Footnotes
    1 The following are members of The Senri Study II Group: Drs. Hideki Asakawa, Toshio Amano, Akira Amenomori, Naoto Itoh, Yasuko Kusaka, Kouhei Kuroda, Kouken Boku, Suguru Sato, Mamiko Tsugawa, Seiichi Sumi, Naoji Takeuchi, Makoto Nakao, Keizo Noma, Atsushi Hirotani, Katsuto Shirouzu, Kosuke Nitta, Mitsuo Midorikawa, Koji Yokokawa and Hiroaki Yoshioka.
      Patients with type 2 diabetes (T2DM) are at substantially higher risk of mortality, primarily from cardiovascular disease, than the general population [
      • Roper N.A.
      • Bilous R.W.
      • Kelly W.F.
      • Unwin N.C.
      • Connolly V.M.
      Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study.
      ]. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) remains the only large-scale, prospective, secondary prevention trial carried out entirely in patients with T2DM [
      • Dormandy J.A.
      • Charbonnel B.
      • Eckland D.J.
      • et al.
      Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.
      ]. This trial provides information of a possible macrovascular benefit with pioglitazone (PGZ), peroxisome proliferators-activated receptor-γ (PPAR-γ) agonists, thiazolidinedione (TZD), particularly in terms of major adverse cardiovascular events, despite only showing a statistical trend towards benefit for the primary composite outcome. However, the driver of the favorable effects of PGZ is still unknown. We previously demonstrated that the favorable effects of PGZ on glucose metabolism are associated with an increase in the circulating fat-derived hormone adiponectin [
      • Maeda N.
      • Takahashi M.
      • Funahashi T.
      • et al.
      PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.
      ,
      • Iwaki M.
      • Matsuda M.
      • Maeda N.
      • et al.
      Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.
      ], possessing an array of antidiabetogenic and cardiovascular protective effects. As well as reducing hyperglycemia, PGZ increases insulin sensitivity and also exerts additional pleiotropic effects on the chronic inflammation and endothelial dysfunction that underlie atherosclerosis [
      • Staels B.
      PPARgamma and atherosclerosis.
      ]. Oxidative stress, induced by intracellular accumulation of reactive oxygen species (ROS), is also causally related to endothelial dysfunction, atherosclerosis, diabetic vasculopathies and beta cell failure in T2DM [
      • Brownlee M.
      The pathobiology of diabetic complications: a unifying mechanism.
      ]. Our study showed that the adipose tissue is the major source of ROS (FatROS), and thus related to the pathophysiology of obesity [
      • Furukawa S.
      • Fujita T.
      • Shimabukuro M.
      • et al.
      Increased oxidative stress in obesity and its impact on metabolic syndrome.
      ]. In rodents, TZD can eliminate oxidative stress both in vitro [
      • Houstis N.
      • Rosen E.D.
      • Lander E.S.
      Reactive oxygen species have a causal role in multiple forms of insulin resistance.
      ] and in vivo [
      • Okuno Y.
      • Matsuda M.
      • Kobayashi H.
      • et al.
      Adipose expression of catalase is regulated via a novel remote PPARgamma-responsive region.
      ,
      • Dobrian A.D.
      • Schriver S.D.
      • Khraibi A.A.
      • Prewitt R.L.
      Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity.
      ]. In the present study, we investigated the effect of treatment with PGZ on circulating thiobarbituric acid-reacting substances (TBARS), markers for systemic ROS production, and adiponectin levels in T2DM patients.

      Keywords

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      References

        • Roper N.A.
        • Bilous R.W.
        • Kelly W.F.
        • Unwin N.C.
        • Connolly V.M.
        Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study.
        BMJ. 2001; 322: 1389-1393
        • Dormandy J.A.
        • Charbonnel B.
        • Eckland D.J.
        • et al.
        Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.
        Lancet. 2005; 366: 1279-1289
        • Maeda N.
        • Takahashi M.
        • Funahashi T.
        • et al.
        PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.
        Diabetes. 2001; 50: 2094-2099
        • Iwaki M.
        • Matsuda M.
        • Maeda N.
        • et al.
        Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.
        Diabetes. 2003; 52: 1655-1663
        • Staels B.
        PPARgamma and atherosclerosis.
        Curr Med Res Opin. 2005; 21: S13-20
        • Brownlee M.
        The pathobiology of diabetic complications: a unifying mechanism.
        Diabetes. 2005; 54: 1615-1625
        • Furukawa S.
        • Fujita T.
        • Shimabukuro M.
        • et al.
        Increased oxidative stress in obesity and its impact on metabolic syndrome.
        J Clin Invest. 2004; 114: 1752-1761
        • Houstis N.
        • Rosen E.D.
        • Lander E.S.
        Reactive oxygen species have a causal role in multiple forms of insulin resistance.
        Nature. 2006; 440: 944-948
        • Okuno Y.
        • Matsuda M.
        • Kobayashi H.
        • et al.
        Adipose expression of catalase is regulated via a novel remote PPARgamma-responsive region.
        Biochem Biophys Res Commun. 2008; 366: 698-704
        • Dobrian A.D.
        • Schriver S.D.
        • Khraibi A.A.
        • Prewitt R.L.
        Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity.
        Hypertension. 2004; 43: 48-56
        • Examination Committee of Criteria for ‘Obesity Disease’ in Japan
        • Japan Society for the Study of Obesity
        New criteria for ‘obesity disease’ in Japan.
        Circ J. 2002; 66: 987-992
        • Yagi K.
        A simple fluorometric assay for lipoperoxide in blood plasma.
        Biochem Med. 1976; 15: 212-216
        • Fujita K.
        • Nishizawa H.
        • Funahashi T.
        • Shimomura I.
        • Shimabukuro M.
        Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome.
        Circ J. 2006; 70: 1437-1442
        • Okuno Y.
        • Matsuda M.
        • Miyata Y.
        • et al.
        Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element distinct from that of mouse.
        Endocr J. 2010; 57: 303-309
        • Fujita K.
        • Maeda N.
        • Sonoda M.
        • et al.
        Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha.
        Arterioscler Thromb Vasc Biol. 2008; 28: 863-870
        • Ohashi K.
        • Iwatani H.
        • Kihara S.
        • et al.
        Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice.
        Arterioscler Thromb Vasc Biol. 2007; 27: 1910-1917