Research Article| Volume 54, ISSUE 4, P529-532, April 2005

Improvement of liver function parameters in patients with type 2 diabetes treated with thiazolidinediones


      To increase our understanding of the effect of thiazolidinediones, a new class of antidiabetic drugs, on liver function as well as glycemic control, we investigated liver function before, during, and after treatment with troglitazone and pioglitazone.
      A total of 32 patients with type 2 diabetes were studied. Glycemic control and liver function were measured before, during, and after 4 to 12 weeks of treatment with troglitazone or pioglitazone. Glycemic control was assessed by fasting levels of plasma glucose, hemoglobin A1c, and serum insulin, and liver function was assessed by asparatate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP). Homeostasis model assessment for insulin resistance was used as an index of insulin resistance.
      During treatment with troglitazone, fasting plasma glucose and hemoglobin A1c levels and homeostasis model assessment for insulin resistance were significantly decreased. Serum AST, ALT, and γ-GTP levels were significantly decreased during treatment (AST, −17.4%; ALT, −27.2%; γ-GTP, −47.9%) and returned to pretreatment levels after 4 weeks of withdrawal of the drug. A similar tendency was observed during treatment with pioglitazone (AST, −4.7%; ALT, −16.4%; γ-GTP, −30.8%).
      These data suggest that, in contrast to the deterioration of liver function reported in a small subset of patients treated with troglitazone, treatment with thiazolidinediones was associated with a decrease in serum transaminases in most patients. The improvement in liver function parameters known to be associated with fatty liver in the present study, together with an improvement in fatty liver reported for another class of insulin sensitizers, biguanides, suggests that thiazolidinediones may have a beneficial effect on fatty liver.
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        • Saltiel A.R.
        • Olefsky J.M.
        Thiazolidinediones in the treatment of insulin resistance and type II diabetes.
        Diabetes. 1996; 45: 1661-1669
        • Iwamoto Y.
        • Kosaka K.
        • Kuzuya T.
        • Akanuma Y.
        • Shigeta Y.
        • Kaneko T.
        Effect of troglitazone: a new hypoglycemic agent in patients with NIDDM poorly controlled by diet therapy.
        Diabetes Care. 1996; 19: 151-156
        • Aronoff S.
        • Rosenblatt S.
        • Braithwaite S.
        • Egan J.W.
        • Mathisen A.L.
        • Schneider R.L.
        • The Pioglitazone 001 Study Group
        Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study.
        Diabetes Care. 2000; 23: 1605-1611
        • Watkins P.B.
        • Whitconb R.W.
        Hepatic dysfunction associated with troglitazone.
        N. Engl. J. Med. 1998; 338: 916-917
        • Gitlin N.
        • Julie N.L.
        • Spurr C.L.
        • Lim K.N.
        • Juarbe H.M.
        Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone.
        Ann. Intern. Med. 1998; 129: 36-38
        • Neuschwander-Tetri B.A.
        • Isley W.L.
        • Oki J.C.
        • Ramrakhiani S.
        • Quiason S.G.
        • Phillips N.J.
        • et al.
        Troglitazone-induced hepatic failure leading to liver transplantation. A case report.
        Ann. Intern. Med. 1998; 129: 38-41
        • Shibuya A.
        • Watanabe M.
        • Fujita Y.
        • Saigenji K.
        • Kuwano S.
        • Takahashi H.
        • et al.
        An autopsy case of troglitzazone-induced fulminant hepatitis.
        Diabetes Care. 1998; 21: 2140-2143
        • Lin H.Z.
        • Yang S.Q.
        • Chuckaree C.
        • Kuhajda F.
        • Ronnet G.
        • Diehl A.M.
        Metformin reverses fatty liver disease in obese, leptin-deficient mice.
        Nat. Med. 2000; 6: 998-1003
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • Naylor B.A.
        • Treacher D.F.
        • Turner R.C.
        Homeostatic model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 2001; 28: 412-419
        • Kosaka K.
        • Kuzuya T.
        • Akanuma Y.
        • Shigeta Y.
        • Kaneko T.
        Clinical evaluation of a new oral hypoglycemic drug CS-045 in patients with non-insulin dependent diabetes mellitus poorly controlled by diet alone—a double blind, placebo-controlled study.
        Rinsho Iyaku. 1993; 9: 61-93
        • Kaneko T.
        • Baba S.
        • Shitiri M.
        Clinical evaluation of the long term efficacy of AD-4833 in patients with non-insulin dependent diabetes mellitus: phase II study.
        Rinsho to Kenkyu. 1997; 74 ([in Japanese]): 231-262
        • Kaneko T.
        • Baba S.
        • Shitiri M.
        Clinical evaluation of the long term efficacy of AD-4833 in patients with non-insulin dependent diabetes mellitus: phase III study.
        Rinsho To Kenkyu. 1997; 74 ([in Japanese]): 263-287
        • Goto T.
        • Omura T.
        • Takebe K.
        • Kral J.G.
        The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects.
        Int. J. Obes. 1995; 19: 841-845
        • Banerji M.A.
        • Buckley M.C.
        • Chaiken R.L.
        • Gordon D.
        • Lebowitz H.E.
        • Kral J.G.
        Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM.
        Int. J. Obes. 1995; 19: 846-850
        • Marchesini G.
        • Brizi M.
        • Morselli-Labate A.M.
        • Bianchi G.
        • Bugianesi E.
        • McCullough A.J.
        • et al.
        Association of non-alcoholic fatty liver disease to insulin resistance.
        Am. J. Med. 1999; 107: 450-455
        • Marchesini G.
        • Brizi M.
        • Bianchi G.
        • Tomassetti S.
        • Bugianesi E.
        • Lenzi M.
        • et al.
        Non-alcoholic fatty liver disease: a feature of the metabolic syndrome.
        Diabetes. 2001; 50: 1844-1850
        • Katoh S.
        • Hata S.
        • Matsushima M.
        • Ikemoto S.
        • Inoue Y.
        • Yokoyama J.
        • et al.
        Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy—a randomized controlled trial.
        Metabolism. 2001; 50: 414-417
        • Bajaj M.
        • Suraamornkul S.
        • Pratipanawatr T.
        • Hardies L.J.
        • Pratipanawatr W.
        • Glass L.
        • et al.
        Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes.
        Diabetes. 2003; 52: 1364-1370
        • Fulgencio J.-P.
        • Kohl C.
        • Girard J.
        • Pegorier J.-P.
        Troglitazone inhibits fatty acid oxidation and esterification, and gluconeogenesis in isolated hepatocytes from starved rats.
        Diabetes. 1996; 45: 1556-1562
        • Kelly I.E.
        • Han T.S.
        • Walsh K.
        • Lean M.E.J.
        Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.
        Diabetes Care. 1999; 22: 288-293