Biomarkers and Outcomes in the Diabetes Prevention Program

描述(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，但糖尿病对健康的影响和经济负担仍在继续扩大。糖尿病预防计划(DPP)确定了糖尿病的高危人群，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有效；DPP结果研究(DPPOS)正在进行的研究正在审查这些干预措施的长期影响。这项建议旨在评估DPP和DPPOS中新的生物标志物水平。这些生物标志物以目前DPP/DPPOS的设计为基础，以纵向方式反映了被认为在糖尿病及其血管并发症的发展中重要的病理生理途径。利用基线和1年DPP时间点和进入DPPOS时的储存血液样本，本项目的具体目标是调查(1)干预对生物标记物的影响(2)生物标记物预测和干预对糖尿病发展的影响，及其共病(3)糖尿病的基线生物标记物和预测微血管和大血管并发症(4)糖尿病发病时的生物标记物水平和并发症的预测。已选择炎症(CRP、IL-6、MCP-1、TNFα)、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)、代谢紊乱(脂联素、载脂蛋白B、瘦素)和胱抑素C等生物标志物进行检测。生物标记物水平从DPP基线到1年的变化将评估干预对生物标记物的影响，反映干预前、治疗1年和较长期治疗效果的所有三种生物标记物评估将确定生物标记物对糖尿病及其并发症的发展的预测价值。越来越多的研究表明，炎症、凝血和血管功能障碍的循环生物标志物提供了这些过程在慢性病中所起作用的一种衡量标准。这项建议将在糖尿病及其并发症的高危人群中提供有关糖尿病及其并发症发生的疾病途径的新信息，从而为2型糖尿病及其并发症的发展创造更好的预测和治疗方法的机会。

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.