Biomarkers in the progression of nephropathy in type 2DM

2 型糖尿病肾病进展中的生物标志物

基本信息

批准号：
7294451
负责人：
JULIE LIN
金额：
$ 8.75万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7294451
关键词：
Affect Age Albumins Albuminuria Biological Assay Biological Markers Biology Blood Body mass index C-reactive protein Characteristics Cholesterol Chronic Disease Chronic Kidney Failure Clinical Investigator Collection Creatinine Cross-Sectional Studies Data Diabetes Mellitus Diffuse Disease regression Dyslipidemias End stage renal failure Fibrinogen Functional disorder Funding Future Glomerular Filtration Rate Goals Grant High Density Lipoproteins Hypertension Hypertriglyceridemia Inflammation Inflammatory Insulin Resistance Investigation Kidney Kidney Diseases Kidney Failure Lipids Measurement Measures Microalbuminuria Monitor Non-Insulin-Dependent Diabetes Mellitus Nurses&apos Health Study Participant Pharmaceutical Preparations Plasma Play Prospective Studies Renal function Role Spottings Testing Time Tumor Necrosis Factor-alpha Tumor Necrosis Factors United States Urine Woman Work cigarette smoking cohort cost follow-up human TNF protein interest low density lipoprotein triglyceride urinary vascular endothelial dysfunction vascular inflammation

项目摘要

DESCRIPTION (provided by applicant): There is a growing recognition that dyslipidemia and elevated inflammatory biomarkers are associated with nephropathy as well as with the insulin-resistant state characteristic of type 2 diabetes. Most investigations, however, have examined these biomarkers and kidney function only in those with severe chronic kidney disease or end-stage renal disease in a cross-sectional manner. A few recent studies suggest that dyslipidemia and inflammation may contribute to subsequent glomerular filtration rate (GFR) decline, but only baseline biomarkers have been examined in this context. The effects of how alterations in lipids and inflammation over time affect kidney function over time are not known. This prospective study seeks to expand on currently funded work that focuses on identifying predictors of progressive nephropathy in type 2 diabetes, which is the leading cause of kidney failure in the world. The central hypothesis is that increasing or sustained high levels of dyslipidemia and inflammation over 11 years (1989 to 2000) will be independently associated with progressive nephropathy, as measured by estimated GFR decline and increased albuminuria over a subsequent eight years of follow-up (2000 to 2008), in 500 women with confirmed type 2 diabetes who are participating in the Nurses' Health Study (NHS). Biomarkers of interest in this investigation include total cholesterol, low-density lipoprotein, triglycerides, high-density lipoproteins, soluble tumor necrosis factor-(, fibrinogen, and C-reactive protein. Several of these biomarkers are significantly inversely associated with estimated GFR in preliminary cross-sectional studies in this NHS cohort. Multivariable regression will be used to adjust for important covariates such as age, duration of diabetes, body mass index, hypertension, cigarette smoking and other medication use, which may confound associations between biomarkers and progressive nephropathy in type 2 diabetes. Data on how these modifiable biomarkers are related to kidney function decline could have an important and beneficial impact on treatment and monitoring of nephropathy in type 2 diabetes in the near future.

描述（由申请人提供）：人们越来越认识到血脂异常和炎症生物标志物升高与肾病以及 2 型糖尿病的胰岛素抵抗状态特征相关。然而，大多数研究仅以横断面的方式检查了患有严重慢性肾病或终末期肾病的患者的这些生物标志物和肾功能。最近的一些研究表明，血脂异常和炎症可能导致随后的肾小球滤过率（GFR）下降，但在这方面仅检查了基线生物标志物。随着时间的推移，脂质和炎症的变化如何影响肾功能尚不清楚。这项前瞻性研究旨在扩展目前资助的工作，重点是确定 2 型糖尿病进展性肾病的预测因素，2 型糖尿病是世界上肾衰竭的主要原因。中心假设是，在 11 年（1989 年至 2000 年）内，血脂异常和炎症的增加或持续高水平将与进行性肾病独立相关，通过随后八年的随访（2000 年）估计的 GFR 下降和蛋白尿增加来衡量到 2008 年），调查对象为 500 名参加护士健康研究 (NHS) 的确诊患有 2 型糖尿病的女性。本研究中感兴趣的生物标志物包括总胆固醇、低密度脂蛋白、甘油三酯、高密度脂蛋白、可溶性肿瘤坏死因子、纤维蛋白原和 C 反应蛋白。其中一些生物标志物与初步估计的 GFR 显着负相关。该 NHS 队列的横断面研究将用于调整重要的协变量，例如年龄、糖尿病病程、体重指数、高血压、吸烟和其他药物治疗。的使用，这可能会混淆生物标志物与 2 型糖尿病进展性肾病之间的关联。有关这些可修改的生物标志物如何与肾功能下降相关的数据可能会对不久的将来 2 型糖尿病肾病的治疗和监测产生重要且有益的影响。