Tolman K G
University of Utah School of Medicine, Salt Lake City, Utah, USA.
Int J Clin Pract Suppl. 2000 Oct(113):29-34.
Type 2 diabetes mellitus, which affects approximately 7% of the population, is a disease of relative insulin insufficiency manifested by insulin resistance in skeletal muscle, liver and adipose tissue. This results in increased hepatic glucose production with compensatory hyperinsulinaemia. The secondary hyperinsulinaemia is associated with an increased incidence of hepatocellular carcinoma and non-alcoholic steatohepatitis (NASH). It is estimated that insulin resistance is present in 50-70% of patients with NASH and that the incidence of NASH in type 2 diabetes is 60-80%. The prevalence of cirrhosis in established type 2 diabetes is as high as 10% and the prevalence of hepatitis C is 3-11%. It was in this setting that the insulin sensitisers were developed. The thiazolidinediones represent a significant and unique pharmacological breakthrough for the management of type 2 diabetes mellitus. The first of the drugs, troglitazone, proved to be hepatotoxic and has been withdrawn from the market. Two cases of hepatotoxicity of rosiglitazone have been reported. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. However, it appears that the incidence of hepatotoxicity of rosiglitazone is much lower than that of troglitazone. It is not yet known if any hepatotoxicity occurs with pioglitazone.
2型糖尿病影响着约7%的人口，是一种相对胰岛素不足的疾病，表现为骨骼肌、肝脏和脂肪组织中的胰岛素抵抗。这导致肝脏葡萄糖生成增加并伴有代偿性高胰岛素血症。继发性高胰岛素血症与肝细胞癌和非酒精性脂肪性肝炎（NASH）的发病率增加有关。据估计，50%-70%的NASH患者存在胰岛素抵抗，2型糖尿病患者中NASH的发病率为60%-80%。在已确诊的2型糖尿病中，肝硬化的患病率高达10%，丙型肝炎的患病率为3%-11%。正是在这种背景下，胰岛素增敏剂得以研发。噻唑烷二酮类药物是2型糖尿病治疗方面一项重大且独特的药理学突破。第一种此类药物曲格列酮被证明具有肝毒性，已退出市场。已有两例罗格列酮肝毒性的报道。目前尚不清楚肝毒性是该类药物的共性还是与曲格列酮独特的生育酚侧链有关。然而，罗格列酮的肝毒性发生率似乎远低于曲格列酮。吡格列酮是否会导致肝毒性尚不清楚。
