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

• 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
• 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' 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

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升高的炎性生物标志物与肾病以及2型糖尿病的胰岛素耐药性特征有关。然而，大多数研究仅在患有严重慢性肾脏疾病或终末期肾脏疾病的患者中检查了这些生物标志物和肾脏功能。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，但在这种情况下仅检查了基线生物标志物。尚不清楚脂质和炎症随着时间的变化影响肾脏功能的影响。 这项前瞻性研究旨在扩大目前资助的工作，该工作着重于确定2型糖尿病中进行性肾病的预测因子，这是世界上肾脏衰竭的主​​要原因。中心假设是，在500名随后的妇女（2000年至2008年）中，在500名型糖尿病的妇女中，在500名妇女中，在500名妇女中，在500名妇女中，在500名型糖尿病中，培训（2000年至2008年）在研究（NARH SURTATE）中，在500名妇女中，在500名妇女中，在500名妇女中，估计的蛋白尿量增加了11年（1989年至2000年）在11年（1989年至2000年）中与进行性肾病独立相关。这项研究中感兴趣的生物标志物包括总胆固醇，低密度脂蛋白，甘油三酸酯，高密度脂蛋白，可溶出的肿瘤坏死因子（，纤维蛋白原和C-反应蛋白）。这些生物标志物中的几种与估计的跨度跨度研究无关紧要。重要的协变量，例如年龄，糖尿病的持续时间，体重指数，高血压，吸烟和其他药物使用，这可能会使生物标志物与2型糖尿病中的渐进性肾病之间的关联混淆，这些糖尿病与这些可修改的生物标志物在肾脏功能下的下降如何相关。