Biomarkers and Outcomes in the Diabetes Prevention Program

糖尿病预防计划中的生物标志物和结果

• 批准号: 7821189
• 负责人: Ronald B Goldberg
• 金额: $ 50.51万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7821189
• 关键词: Ankle; Apolipoproteins B; Biological Markers; Blood Pressure; Blood Vessels; Blood specimen; Body Weight; Body Weight decreased; Body fat; CCL2 gene; Chronic Disease; Coagulants; Coagulation Process; Comorbidity; Complications of Diabetes Mellitus; Controlled Clinical Trials; Coronary heart disease; Development; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Diet; Disease; Disease Pathway; E-Selectin; Economic Burden; Epidemiology; Equilibrium; Fibrinogen; Follow-Up Studies; Functional disorder; Glucose; Goals; Health; Individual; Inflammation; Intercellular adhesion molecule 1; Interleukin-6; Intervention; Kidney Diseases; Leptin; Life Style; Lipids; Long-Term Effects; Measurement; Measures; Mediator of activation protein; Metabolic; Metabolic Marker; Metabolic syndrome; Metformin; Methods; Myocardial Infarction; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Study; Pathway interactions; Peripheral Vascular Diseases; Persons; Physical activity; Placebos; Plasminogen Activator Inhibitor 1; Predictive Value; Prevention; Process; Randomized Clinical Trials; Resistance; Retinal Diseases; Risk; Risk Factors; Role; Stroke; Testing; Thick; Time; Translating; Visit; adiponectin; cohort; design; diabetes prevention program; disorder risk; economic impact; effective intervention; follow-up; health economics; high risk; improved; indexing; inflammatory marker; insulin secretion; insulin sensitivity; intervention effect; intima media; lifestyle intervention; macrovascular disease; novel; post gamma-globulins; prevent; therapeutic target; treatment effect

DESCRIPTION (provided by applicant): Despite advances in the treatment of type 2 diabetes and its Complications, the health impact and economic burden of diabetes continues to expand. The Diabetes Prevention Program (DPP) identified persons at high risk for diabetes and showed that lifestyle and pharmacologic intervention strategies were effective in preventing or delaying the development of diabetes; ongoing studies in the DPP Outcome Study (DPPOS) are examining the long-term impact of these interventions. This proposal is aimed at assessing novel biomarker levels in DPP and DPPOS. These biomarkers reflect pathophysiological pathways considered important in the development of diabetes and its vascular complications in a longitudinal manner, building on the current design of DPP/DPPOS. Using stored blood samples at the baseline and 1-year DPP time points and at entry into DPPOS, the specific aims of this projects are to investigate (1) The effects of interventions on biomarkers (2) Biomarker prediction and intervention effects on development of diabetes, and its co-morbidities (3) Baseline biomarkers and prediction of microvascular and macrovascular complications of diabetes (4) Biomarker levels at diabetes onset and prediction of complications. Biomarkers of inflammation (CRP, IL-6, MCP-1, TNFalpha), coagulant balance (PAI-1, fibrinogen, tPA), endothelial dysfunction (sICAM-1, sVCAM-1, E-selectin) and of metabolic deregulation (adiponectin, apo B, leptin) and cystatin C have been selected for measurement. Change in biomarker levels from DPP baseline to 1 year will assess effects of interventions on biomarkers, and all three biomarker assessments, reflecting pre-intervention, 1-year on-treatment and longer-term on-treatment effects will determine the predictive value of biomarkers on development of diabetes and its complications. Circulating biomarkers of inflammation, coagulation and vascular dysfunction are increasingly being shown to provide a measure of the role of these processes in chronic diseases. This proposal will provide novel information on the disease pathways involved in the development of diabetes and its complications in subjects at high risk for this disease and thereby create improved opportunities for prediction and methods of treatment in the development of type 2 diabetes and its complications.

描述（由申请人提供）：尽管2型糖尿病及其并发症的治疗取得了进展，但糖尿病的健康影响和经济负担仍在继续扩大。糖尿病预防计划（DPP）确定了糖尿病高危人群，并表明生活方式和药物干预策略在预防或延缓糖尿病发展方面是有效的；正在进行的DPP结果研究（DPPOS）正在检查这些干预措施的长期影响。本提案旨在评估DPP和DPPOS中新的生物标志物水平。这些生物标志物在DPP/DPPOS当前设计的基础上，以纵向方式反映了在糖尿病及其血管并发症发展中被认为重要的病理生理途径。使用基线和1年DPP时间点以及进入DPPOS时储存的血液样本，本项目的具体目的是研究(1)干预对生物标志物的影响(2)生物标志物预测和干预对糖尿病发展及其合并症的影响(3)基线生物标志物和糖尿病微血管和大血管并发症的预测(4)糖尿病发病时的生物标志物水平和并发症的预测。炎症（CRP, IL-6, MCP-1, TNFalpha），凝血平衡（PAI-1，纤维蛋白原，tPA），内皮功能障碍（sICAM-1, sVCAM-1， e -选择素）和代谢失调（脂联素，载脂蛋白B，瘦素）和胱抑素C的生物标志物已被选择用于测量。生物标志物水平从DPP基线到1年的变化将评估干预对生物标志物的影响，所有三种生物标志物评估，反映干预前、治疗1年和长期治疗效果，将决定生物标志物对糖尿病及其并发症发展的预测价值。炎症、凝血和血管功能障碍的循环生物标志物越来越多地被证明可以衡量这些过程在慢性疾病中的作用。本研究将为糖尿病高危人群的糖尿病及其并发症的发病途径提供新的信息，从而为2型糖尿病及其并发症的发展提供更好的预测和治疗方法。

项目成果

Accelerated atherosclerosis and elevated lipoprotein (a) after liver transplantation.

肝移植后动脉粥样硬化加速和脂蛋白升高 (a)。

• DOI: 10.1016/j.jacl.2015.12.022
• 发表时间: 2016
• 期刊: Journal of clinical lipidology
• 影响因子: 4.4
• 作者: Damluji,AbdullaA;El-Maouche,Diala;Alsulaimi,Ali;Martin,Paul;Shamburek,RobertD;Goldberg,RonaldB;Baum,SethJ;deMarchena,EduardoJ
• 通讯作者: deMarchena,EduardoJ

Erratum to: "Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the diabetes prevention program" [Metabolism (2016) 65; 764-775].

勘误：“脂联素的变化解释了生活方式干预引起的 HDL 颗粒的大部分变化，但不能解释糖尿病预防计划中的二甲双胍治疗”[Metabolism (2016) 65；

• DOI: 10.1016/j.metabol.2016.11.007
• 发表时间: 2017
• 期刊: Metabolism: clinical and experimental
• 作者: Goldberg,RonaldB;Temprosa,Marinella;Mele,Lisa;Orchard,Trevor;Mather,Kieren;Bray,George;Horton,Edward;Kitabchi,Abbas;Krakoff,Jonathan;Marcovina,Santica;Perreault,Leigh;White,Neil;DiabetesPreventionProgramResearchGroup
• 通讯作者: DiabetesPreventionProgramResearchGroup