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作了广泛的修改。 一些抗精神病药物似乎会增加糖尿病的风险。然而，其他证据提出了精神分裂症与不使用抗精神病药物的糖尿病风险增加有关的可能性。最近的一项重要研究发现，与对照组相比，未接受药物治疗的新诊断的精神分裂症患者的胰岛素抵抗增加，但同一研究还发现精神分裂症受试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，因此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所致。其他混杂因素也可能在以前的研究中起作用。 我们建议进行两项研究。1)我们将对4组在性别、年龄、体重指数和某些生活方式变量上匹配的受试者进行葡萄糖耐量试验：未接受过药物治疗、最近诊断为精神分裂症的受试者;抑郁症受试者;适应障碍受试者;对照受试者。我们将检验精神分裂症组与对照组相比胰岛素抵抗增加的假设;纳入其他2组将使我们能够评估高皮质醇血症的作用。我们还将对炎症标志物C-反应蛋白和白细胞介素-6进行探索性分析，它们是糖尿病风险的独立标志物。2)在一项在未接受过药物治疗的新诊断精神病受试者中进行的开放试验中，我们将检验以下假设：治疗前胰岛素抵抗增加预示奥氮平治疗后胰岛素抵抗增加。这些研究将评估精神分裂症是否与糖耐量受损相关，以及该异常是否可预测奥氮平给药后空腹血糖受损的后续风险。

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.