Kishimoto Miyako, Sugiyama Takehiro, Osame Keiichiro, Takarabe Daisuke, Okamoto Masahide, Noda Mitsuhiko
Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
J Med Invest. 2011 Feb;58(1-2):86-94. doi: 10.2152/jmi.58.86.
Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along with common lipid-regulating agents (combination therapy). To evaluate the effect of ezetimibe therapy on the lipid profile, glucose metabolism, and levels of cholesterol absorption and synthesis markers, we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes. The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group. The serum levels of the cholesterol absorption markers were significantly reduced, while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy. No significant differences were noted in the values of the parameters of glucose metabolism in all patients. We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe (ezetimibe responders); however, multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender, age, BMI, diabetic condition, method of ezetimibe administration, and the initial absolute values of cholesterol absorption/synthesis markers levels. In conclusion, ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism. We were unable to identify the specific characteristics of ezetimibe responders among our subjects. However, we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels.
依折麦布可选择性抑制饮食和胆汁中的胆固醇吸收，单独使用（单药治疗）或与常用的血脂调节剂联合使用（联合治疗）时均可降低血清胆固醇水平。为了评估依折麦布治疗对血脂谱、糖代谢以及胆固醇吸收和合成标志物水平的影响，我们对50例有或无糖尿病的高胆固醇血症患者给予10mg依折麦布。在单药治疗组和联合治疗组的糖尿病患者以及联合治疗组的非糖尿病患者中，依折麦布治疗4周和12周时，低密度脂蛋白胆固醇和总胆固醇的血清水平均显著降低。依折麦布治疗12周时，胆固醇吸收标志物的血清水平显著降低，而胆固醇合成标志物的血清水平显著升高。所有患者的糖代谢参数值均未发现显著差异。我们还研究了对依折麦布反应良好的患者（依折麦布反应者）的临床特征；然而，多因素回归分析未发现依折麦布疗效与患者特征（如性别、年龄、BMI、糖尿病状况、依折麦布给药方法以及胆固醇吸收/合成标志物水平的初始绝对值）之间存在相关性。总之，依折麦布治疗可显著改善血脂谱，且不影响糖代谢。我们未能在研究对象中确定依折麦布反应者的具体特征。然而，我们可以将这一结果解释为提示依折麦布可用于任何人群以降低低密度脂蛋白胆固醇水平。
