Biomarkers and Outcomes in the Diabetes Prevention Program

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）确定了糖尿病高危人群，并表明生活方式和药物干预策略可有效预防或延缓糖尿病的发展; DPP结局研究（DPPOS）正在进行的研究正在检查这些干预措施的长期影响。该提案旨在评估DPP和DPPOS中的新生物标志物水平。这些生物标志物反映了在糖尿病及其血管并发症的发展中以纵向方式重要的病理生理学途径，建立在DPP/DPPOS的当前设计基础上。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的影响，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。炎症的生物标志物（CRP、IL-6、MCP-1、TNF α）、凝血平衡（派-1、纤维蛋白原、tPA）、内皮功能障碍（sICAM-1、sVCAM-1、E-选择素）和代谢失调的生物标志物（脂联素、apo B、瘦素）和半胱氨酸蛋白酶抑制剂C已被选择用于测量。生物标志物水平从DPP基线至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、1年治疗中和长期治疗中的影响）将确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显示出提供这些过程在慢性疾病中的作用的量度。该提案将提供关于糖尿病及其并发症的发展中涉及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中的预测和治疗方法创造更好的机会。

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.