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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 高血糖和2型糖尿病在精神分裂症中比普通人群更为常见。 2型糖尿病的特征是胰岛素作用对骨骼肌，肝脏和脂肪组织的干扰。 糖尿病会导致由于急性（例如糖尿病性酮症病）和长期（例如心血管疾病）并发症引起的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更加密切相关。 在引入抗精神病药物药物之前，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会增加。 然而，从那时起，额外的葡萄糖调节异常（例如，新发作糖尿病），血脂异常以及体重和肥胖均与抗精神病药有关。 最近关注对葡萄糖，脂质和肥胖性的抗精神病药作用最近增加了，重点是广泛使用的新药物，氯氮平和奥氮平。 腹部肥胖的增加可以降低胰岛素敏感性，而牙齿肌酸可以增加肥胖性。 然而，药物对葡萄糖控制和胰岛素作用的影响可能与肥胖差异无关。 该项目旨在a）评估选定的抗精神病药对骨骼肌胰岛素作用的影响（葡萄糖处置），肝脏（葡萄糖产生）和脂肪组织（全身脂肪溶解），b）所选抗精神病药对腹部脂肪组织肿块和总体脂肪质量的影响，长期探索的抗精神病药物的影响关于葡萄糖耐量，脂质谱，腹部脂肪组织质量，总脂肪脂肪和总无脂肪的抗精神病药。 这些假设将通过测量1）使用“金标准”稳定的同位素示踪方法，2）使用双能X射线吸收仪和磁共振成像的身体组成，以及3）纵向耐糖耐受性耐受性和脂质涂料。 该目标将在接受利培酮，奥氮平，氯氮平或氟哌啶醇以及未治疗的健康对照的非糖尿病精神分裂症患者中解决。 还将对接受奥氮平和利培酮治疗的患者（从上面的组）进行重新评估，并与其他药物交叉治疗6个月。 相关数据需要针对基础研究，确定长期心血管后果并计划治疗干预措施。