Diabetes in Neuropsychiatric Disorders

描述(由申请人提供)：这是我们第一次重新提交申请。我们的建议已根据审查员的意见进行了广泛的修改。 一些抗精神病药物似乎会增加患糖尿病的风险。然而，其他证据表明，在没有使用抗精神病药物的情况下，精神分裂症与糖尿病风险增加有关。最近的一项重要研究发现，与对照组相比，新近诊断的药物未成熟的精神分裂症患者的胰岛素抵抗增加，但同一项研究也发现，精神分裂症患者的皮质醇浓度比对照组高得多。由于高皮质醇血症可导致胰岛素抵抗，本研究和其他研究中的葡萄糖浓度升高可能是由于高皮质醇血症。其他混杂因素也可能在之前的研究中起作用。 我们建议进行两项研究。1)我们将对性别、年龄、体重指数和某些生活方式变量匹配的4组人进行葡萄糖耐量测试：未服用药物的新近确诊的精神分裂症患者、抑郁症患者、适应障碍患者和对照组。我们将检验这一假设，即精神分裂症组与对照组相比胰岛素抵抗增加；包括其他两组将使我们能够评估高皮质醇血症的作用。我们还将对炎症标记物C-反应蛋白和白介素6进行探索性分析，它们是糖尿病风险的独立标记物。2)在一项针对新药初治精神病患者的公开试验中，我们将检验这样一种假设，即治疗前较大的胰岛素抵抗预示着奥氮平治疗后较大的胰岛素抵抗增加。这些研究将评估精神分裂症是否与糖耐量受损有关，以及这种异常是否预测奥氮平治疗后空腹血糖受损的风险。

DESCRIPTION (provided by applicant): This is a first resubmission of our application. Our proposal has been revised extensively in response to the reviewer's comments. Some antipsychotic medications appear to increase the risk of diabetes. However, other evidence raises the possibility that schizophrenia is associated with an increased risk of diabetes in the absence of antipsychotic use. An important recent study found increased insulin resistance in drug-naive, newly diagnosed patients with schizophrenia compared to controls, but the same study also found much higher cortisol concentrations in the schizophrenia subjects than in the controls. As hypercortisolemia can cause insulin resistance, increased glucose concentrations in this and other studies may have been due to hypercortisolemia. Other confounding factors also may have operated in previous research. We propose to conduct 2 studies. 1) We will administer a glucose tolerance test to 4 groups matched on gender, age, body mass index, and certain lifestyle variables: drug-naive, recently diagnosed schizophrenia subjects; subjects with depression; subjects with adjustment disorder; and control subjects. We will test the hypothesis that schizophrenia group increased insulin resistance compared to the control group; inclusion of the other 2 groups will enable us to assess the role hypercortisolemia. We will also conduct exploratory analyses of inflammatory markers C-reactive protein and interleukin-6, which are independent markers of diabetes risk. 2) In an open trial in drug-naive newly diagnosed subjects with psychosis, we will test the hypothesis that greater insulin resistance prior to treatment predicts a larger increase in insulin resistance with olanzapine treatment. These studies will assess whether schizophrenia is associated with impaired glucose tolerance, and whether this abnormality predicts the subsequent risk of impaired fasting glucose with olanzapine administration.