Pylvänen Virpi, Pakarinen Arto, Knip Mikael, Isojärvi Jouko
Department of Neurology, University of Oulu, Oulu, and Hospital for Children and Adolescents, Helsinki, Finland.
Epilepsy Behav. 2006 May;8(3):643-8. doi: 10.1016/j.yebeh.2006.02.008. Epub 2006 Apr 5.
Weight gain is a known side effect of valproate (VPA) therapy, which is associated with hyperinsulinemia and polycystic ovary-like syndrome and unfavorable lipid changes in women. Hyperinsulinemia has also been observed in male and lean subjects as well. Hyperinsulinemia is associated with several health risks, such as cardiovascular diseases and the metabolic syndrome. The purpose of this study was to evaluate whether VPA-related hyperinsulinemia is associated with other metabolic changes and whether there is any association between weight gain, other adverse effects related to VPA, and the metabolic syndrome. Fifty-one patients under VPA monotherapy and 45 healthy control subjects participated in the study. They were interviewed and clinically examined, and, after an overnight fast, blood samples were taken to evaluate fasting serum insulin, lipid, free fatty acid, and uric acid levels. Incidence of the metabolic syndrome was determined as well. Compared with control subjects, VPA-treated patients had higher circulating insulin concentrations relative to body mass index, higher uric acid and triglyceride levels, and lower high-density lipoprotein cholesterol concentrations. There was no significant difference in the frequency of the metabolic syndrome between the VPA-treated patient group and the control group. In conclusion, valproate therapy, especially if started at a young age, is associated with increased circulating insulin concentrations relative to body mass index, indicating that the high insulin levels are not a consequence of obesity. Although the frequency of the metabolic syndrome did not differ between VPA-treated patients and control subjects, VPA-treated patients had higher concentrations of triglycerides and uric acid and lower levels of high-density lipoprotein cholesterol than control subjects.
体重增加是丙戊酸盐（VPA）治疗已知的副作用，这与女性的高胰岛素血症、多囊卵巢样综合征以及不利的血脂变化有关。在男性和体型偏瘦的受试者中也观察到了高胰岛素血症。高胰岛素血症与多种健康风险相关，如心血管疾病和代谢综合征。本研究的目的是评估VPA相关的高胰岛素血症是否与其他代谢变化相关，以及体重增加、VPA相关的其他不良反应与代谢综合征之间是否存在关联。51例接受VPA单药治疗的患者和45名健康对照受试者参与了该研究。他们接受了访谈和临床检查，在禁食过夜后采集血样，以评估空腹血清胰岛素、血脂、游离脂肪酸和尿酸水平。同时还确定了代谢综合征的发病率。与对照受试者相比，接受VPA治疗的患者相对于体重指数而言循环胰岛素浓度更高、尿酸和甘油三酯水平更高，而高密度脂蛋白胆固醇浓度更低。VPA治疗患者组和对照组之间代谢综合征的发生率没有显著差异。总之，丙戊酸盐治疗，尤其是在年轻时开始治疗，与相对于体重指数而言循环胰岛素浓度升高有关，这表明高胰岛素水平不是肥胖的结果。虽然VPA治疗患者和对照受试者之间代谢综合征的发生率没有差异，但VPA治疗患者的甘油三酯和尿酸浓度高于对照受试者，而高密度脂蛋白胆固醇水平低于对照受试者。
