Gene Expression and Diagnosis of Diabetes

描述（由申请人提供）：自身免疫性疾病很难诊断，因为症状可能是非特异性的。一个单一的测试，可以很容易地区分自身免疫性和非自身免疫性疾病将允许医生集中精力对影响病人的特定疾病。这对于糖尿病（DM）至关重要，DM有两个子集，I型和II型。糖尿病各亚型在发病机制、治疗和预后方面存在差异。利用微阵列技术，我们比较了自身免疫性糖尿病（包括I型糖尿病）和非自身免疫性II型糖尿病患者外周血单核细胞基因表达的差异。在第一阶段，我们研究了成人和儿童糖尿病类型之间的基因表达差异。这些研究的结果表明，我们可以很容易地根据基因表达模式识别患者的亚组。我们第二阶段应用的目标是使这些诊断测试更接近市场。我们有以下四个具体目标： I.我们将使用来自不同种族背景（高加索人，非洲裔美国人和西班牙裔）和不同地理位置的糖尿病患者的更大队列来扩展我们的微阵列分析，以验证我们的结果，并进一步测试两类I型糖尿病存在于人群中的概念。 二.我们建议，以验证身份的克隆表现出极端的杂交之间的控制和不同的疾病组，并开发“微型微阵列”和定量PCR测试，区分不同的疾病组。 三.我们将通过分析来自一大群对照组和糖尿病个体的血液样本来测试这些平台。 四.我们将在一组最初诊断为高血糖症的个体中验证诊断测试。 长期目标是利用微阵列实验的结果来开发对自身免疫性和非自身免疫性疾病个体的治疗管理具有预测价值的测试。这些包括对疾病进行分类，预测严重程度和预测最佳治疗方案的测试。

DESCRIPTION (provided by applicant): Autoimmune diseases are difficult to diagnose, as the symptoms can be nonspecific. A single test that could readily distinguish between an autoimmune and non-autoimmune disorder would allow physicians to focus efforts on the specific disease that affects the patient. This is critical for diabetes mellitus (DM), which has two subsets, Type I and Type II. The subsets of DM differ in pathogenesis, treatment and prognosis. Using microarray technology, we have compared differences in gene expression in peripheral blood mononuclear cells among patients with autoimmunity, including type I DM, and patients with non-autoimmune Type II DM. In Phase I, we investigated differences in gene expression between the DM types in adults and children. The findings from these studies suggest that we can readily identify subgroups of patients based on the gene expression patterns. The goal of our phase II application is to take these diagnostic tests closer to the marketplace. We have the following four specific aims: I. We will expand our microarray analysis using a larger cohort of individuals with diabetes from different racial backgrounds (Caucasian, African-American, and Hispanic) and different geographical locations to validate our results and to further test the notion that two classes of type I diabetes exist in the human population. II. We propose to validate identity of clones that exhibit extremes in hybridization among the control and different disease groups and develop "mini-microarray" and quantitative PCR tests that distinguish among the different disease groups. III. We will test these platforms by analyzing blood samples from a large cohort of control and diabetic individuals. IV. We will validate the diagnostic test in a cohort of individuals with an initial diagnosis of hyperglycemia. Long-term goals are to use results from microarray experiments to develop tests that have predictive value for the therapeutic management of individuals with autoimmune and non-autoimmune diseases. These include tests that classify diseases, predict severity, and predict optimal therapeutic options.