GLUCOSE AND LIPID METABOLISM ON ANTIPSYCHOTIC MEDICATION

抗精神病药物中的葡萄糖和脂质代谢

• 批准号: 7603312
• 负责人: JOHN W. NEWCOMER
• 金额: $ 2.93万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603312
• 关键词: Abdomen; Acute; Address; Adipose tissue; Antipsychotic Agents; Basic Science; Body Composition; Body fat; Cardiovascular Diseases; Cardiovascular system; Clozapine; Computer Retrieval of Information on Scientific Projects Database; Data; Diabetes Mellitus; Dyslipidemias; Evaluation; Fatty acid glycerol esters; Funding; General Population; Genetic Crossing Over; Glucose; Gold; Grant; Haloperidol; Hyperglycemia; Institution; Insulin; Kinetics; Lipids; Lipolysis; Liver; Magnetic Resonance Imaging; Measures; Methodology; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Pharmaceutical Preparations; Research; Research Personnel; Resources; Risk; Risperidone; Schizophrenia; Skeletal Muscle; Source; Standards of Weights and Measures; Therapeutic Intervention; Tracer; United States National Institutes of Health; Weight Gain; abdominal fat; blood glucose regulation; diabetic; glucose disposal; glucose production; glucose tolerance; insulin sensitivity; lipid metabolism; mortality; non-diabetic; olanzapine; stable isotope; treatment effect

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Type 2 diabetes mellitus is characterized by disturbances in insulin action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and mortality due to acute (e.g., diabetic ketacidosis) and long-term (e.g., cardiovascular disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal adiposity is even more strongly associated with increased cardiovascular morbidity and mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications, suggesting that these patients may be at increased risk. Since then, however, additional glucoregulatory abnormalities (e.g., new onset diabetes), dyslipidemia, and increased weight and adiposity have all been associated with antipsychotic medications. Concern about antipsychotic effects on glucose, lipids and adiposity has increased recently, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and anipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may alos occur independent of differences in adiposity. This project aims to a) evaluate the effects of selected antipsychoitc medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total bady fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients treated with olanzapine and risperidone (from groups above), crossed over to treatment with the other agent for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 高血糖和 2 型糖尿病在精神分裂症患者中比在普通人群中更常见。 2 型糖尿病的特征是胰岛素对骨骼肌、肝脏和脂肪组织的作用紊乱。 糖尿病由于急性（例如糖尿病酮酸中毒）和长期（例如心血管疾病）并发症而导致发病率和死亡率增加。 高血糖、血脂异常和腹部肥胖的结合与心血管发病率和死亡率的增加密切相关。 在引入抗精神病药物之前，人们首先注意到 2 型糖尿病和高血糖与精神分裂症的关联，这表明这些患者的风险可能增加。 然而，从那时起，额外的血糖调节异常（例如新发糖尿病）、血脂异常以及体重和肥胖增加都与抗精神病药物有关。 最近，人们越来越担心抗精神病药物对血糖、血脂和肥胖的影响，重点关注广泛使用的新型药物氯氮平和奥氮平。 腹部肥胖增加会继而降低胰岛素敏感性，而抗精神病药物会增加肥胖。 然而，药物对血糖控制和胰岛素作用的影响也可能与肥胖的差异无关。 该项目旨在 a) 评估选定的抗精神病药物对骨骼肌（葡萄糖处理）、肝脏（葡萄糖产生）和脂肪组织（全身脂肪分解）中胰岛素作用的影响，b) 选定的抗精神病药物对腹部脂肪的影响组织质量、全身脂肪和总去脂质量，以及 c) 探索所选抗精神病药物治疗对葡萄糖耐量、血脂、腹部脂肪组织质量、总坏脂肪的纵向影响和总去脂质量。 这些假设将通过以下方式进行评估：1) 使用“金标准”稳定同位素示踪方法测量全身葡萄糖和脂质动力学，2) 使用双能 X 射线吸收测定法和磁共振成像测量身体成分，以及 3) 纵向葡萄糖耐量和血脂谱的变化。 这些目标将针对长期接受利培酮、奥氮平、氯氮平或氟哌啶醇治疗的非糖尿病精神分裂症患者以及未经治疗的健康对照组。 还将对接受奥氮平和利培酮（来自上述组）治疗的患者进行重新评估，并交叉接受另一种药物治疗 6 个月。 迫切需要相关数据来开展基础研究、确定长期心血管后果并规划治疗干预措施。