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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 高血压和2型糖尿病在精神分裂症中比在一般人群中更常见。 2型糖尿病的特征在于胰岛素对骨骼肌、肝脏和脂肪组织的作用紊乱。 糖尿病由于急性（例如，糖尿病酮症酸中毒）和长期（例如，心血管疾病）并发症。 高血糖、血脂异常和腹部肥胖的组合与心血管发病率和死亡率的增加甚至更强烈地相关。 2型糖尿病和高血糖症与精神分裂症的关联在抗精神病药物引入之前首次被注意到，这表明这些患者可能处于增加的风险中。 然而，从那时起，额外的葡萄糖调节异常（例如，新发糖尿病）、血脂异常、体重增加和肥胖都与抗精神病药物有关。 抗精神病药物对血糖、血脂和肥胖的影响最近越来越受到关注，主要集中在广泛使用的新药氯氮平和奥氮平上。 腹部肥胖增加可继发性降低胰岛素敏感性，精神病药物可增加肥胖。 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。 本项目的目的是a）评价选定的抗精神病药物对骨骼肌胰岛素作用的影响（葡萄糖处置）、肝脏（葡萄糖生成）和脂肪组织（全身脂解），B）所选抗精神病药物对腹部脂肪组织质量、全身脂肪和总无脂肪质量的影响，和c）探索用所选抗精神病药物治疗对葡萄糖耐量的纵向影响，血脂谱、腹部脂肪组织质量、总体脂和总去脂质量。 这些假设将通过以下方式进行评价：1）使用“金标准”稳定同位素示踪剂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组成，以及3）葡萄糖耐量和脂质谱的纵向变化。 将在长期接受利培酮、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和未接受治疗的健康对照组中探讨该目的。 还将对接受奥氮平和利培酮治疗的患者（来自上述组）进行重新评价，交叉至另一种药物治疗6个月。 迫切需要相关数据来针对基础研究，确定长期心血管后果，并计划治疗干预。