Metabolomic Analysis of Type 1 Diabetic Nephropathy

1 型糖尿病肾病的代谢组学分析

• 批准号: 6951025
• 负责人: M. AMIN ARNAOUT
• 金额: $ 34.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951025
• 关键词: albuminuria; biomarker; clinical research; diabetic nephropathy; high performance liquid chromatography; human subject; insulin dependent diabetes mellitus; mass spectrometry; metabolism; pathologic process; plasma; proteomics

DESCRIPTION (provided by applicant): The goals of this project are to discover metabolomic biomarkers for diabetic nephropathy (DN) in type 1 diabetes mellitus (T1D) patients and to understand the pathophysiology of DN. The study hypotheses are: . 1. There are biochemical changes in the plasma and urine of T1D patients with incipient DN that will manifest before the onset of microalbuminuria; and 2. There are biochemical signatures that indicate which T1D patients are most likely to develop diabetic nephropathy (DN), and therefore who will most benefit from preventative measures. To test these hypotheses, we aim to: 1. Establish methods of sample preparation for metabolic profiling in patients with T1D. We will develop procedures for processing urine samples, as well as optimize current procedures for processing plasma to derive separate fractions suitable for metabolomic and proteomic analysis from the same samples. Five pairs of samples will be used; 2. Assemble a specimen bank for metabolomic and subsequent proteomic analysis of plasma and urine samples from: a. 30 recently diagnosed pre-nephropathic T1D patients, b. 30 pre-nephropathic patients with T1D for five to ten years, c. 30 patients with early nephropathy (microalbuminuria), and d. 30 patients with T1D over twenty years, but no evidence of DN. Patients will not be on antihypertensive medications. 3. Identify metabolic signatures that correlate with the progression of DN by comparing samples from patient groups a, b, and c. 4. Identify metabolic signatures that predict the likelihood of developing DN by comparing samples from patient groups b, c and d. In this manner, we hone to identify potential metabolomic biomarkers worthy of subsequent validation.

描述（由申请人提供）： 本项目的目的是发现1型糖尿病（T1 D）患者糖尿病肾病（DN）的代谢组学生物标志物，并了解DN的病理生理学。研究假设是：。 1.在患有初期DN的T1 D患者的血浆和尿液中存在生化变化，其将在微量白蛋白尿发作之前显现;以及 2.有生化特征表明哪些T1 D患者最有可能发展为糖尿病肾病（DN），因此谁将最受益于预防措施。 为了验证这些假设，我们的目标是： 1.建立用于T1 D患者代谢谱分析的样本制备方法。我们将开发用于处理尿液样本的程序，以及优化用于处理血浆的当前程序，以从相同样本中获得适合于代谢组学和蛋白质组学分析的单独组分。将使用五对样本; 2.收集样本库，用于血浆和尿液样本的代谢组学和后续蛋白质组学分析： a. 30例近期诊断为肾病前期的T1 D患者， B. 30例肾病前期T1 D患者5 - 10年， C. 30例早期肾病（微量白蛋白尿）患者，和 D. 30例T1 D患者超过20年，但无DN证据。 患者将不接受降压药物治疗。 3.通过比较患者组a、B和c的样本，鉴定与DN进展相关的代谢特征。 4.通过比较患者组B、c和d的样本，确定预测发生DN可能性的代谢特征。 以这种方式，我们磨练，以确定潜在的代谢组学生物标志物值得后续验证。