Srisawasdi Pornpen, Vanwong Natchaya, Hongkaew Yaowaluck, Puangpetch Apichaya, Vanavanan Somlak, Intachak Boontarika, Ngamsamut Nattawat, Limsila Penkhae, Sukasem Chonlaphat, Kroll Martin H
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Bangkok 10400, Thailand.
Clin Biochem. 2017 Aug;50(12):678-685. doi: 10.1016/j.clinbiochem.2017.02.003. Epub 2017 Feb 3.
To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs).
In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein.
The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses.
Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment.
评估利培酮治疗的剂量和疗程对自闭症谱系障碍（ASD）儿童及青少年心血管和糖尿病风险生物标志物的影响。
在这项横断面分析中，纳入了总共168例接受基于利培酮方案治疗≥12个月的ASD患者（89%为男性）。对血液样本进行葡萄糖和脂质代谢标志物、脂联素、瘦素、催乳素、皮质醇和高敏C反应蛋白分析。
随着利培酮剂量增加，葡萄糖、胰岛素、催乳素和瘦素的平均浓度以及胰岛素抵抗稳态模型评估（HOMA-IR）显著升高（均P<0.025），但脂联素和皮质醇的平均浓度未升高。通过回归分析，胰岛素、瘦素、催乳素和葡萄糖浓度以及HOMA-IR与剂量显著相关。除脂联素外，其他标志物均未显示出对治疗疗程的依赖性。然而，随着剂量和疗程的增加，胰岛素和瘦素浓度以及HOMA-IR明显升高。治疗剂量和疗程对标准血脂谱和脂蛋白亚类的影响极小。
利培酮治疗以剂量和疗程依赖性方式扰乱了ASD儿童及青少年的葡萄糖稳态和内分泌调节（尤其是瘦素），提示存在瘦素和胰岛素抵抗机制。应密切监测代谢不良反应，尤其是2型糖尿病的发生，特别是在接受高剂量和/或长期利培酮治疗的个体中。
