12/22 Limited Competition for the Continuation of the Diabetes Prevention Program Outcomes Study (DPPOS) - Clinical Center

调节异常（“功能障碍”）有一个很长的时间过程，从最早的 糖尿病前期阶段，到2型糖尿病（T2D）的发作，到临床上糖尿病的发展 可检测的微血管变化和可测量的动脉粥样硬化，以临床表现 并发症伴随发病率和死亡率。糖尿病预防计划（DPP） 专注于糖尿病前期的精神障碍，并显示出强大的有益效果 生活方式干预（ILS）和二甲双胍（MET）与安慰剂（PLBO）相比， 在高危人群（n=3234）中预防或延迟T2D发作3年。 DPP还调查并描述了干预措施、表型和基因型风险 与T2D发展相关的因素，在这些因素的背景下干预措施的效果 风险因素、T2D预防的健康经济学意义以及其他关注的结果。 基于这些结果，DPP生活方式方案得到了广泛实施。民进党 结果研究（DPPOS）探索了DPP中T2D预防的长期效果 队列，桥接糖尿病前期和T2D之间的时期，并检查了 比DPP的3年需要更多的时间来开发。DPPOS显示长期有益 原始干预措施对T2D预防和心血管疾病（CVD）风险的影响 因素发生微血管疾病的风险在发生以下疾病的受试者中显著更高： T2D，并随着病程的延长和糖化血红蛋白（HbA1c）的升高而增加。没有 各治疗组在聚集性微血管病变的患病率方面存在显著差异， 然而，与PLBO和MET相比，ILS显著降低了 女性和HbA1c ≥ 6.5%的患者中存在微血管疾病。 在计划第三期延长一年期间，我们会维持及继续遵循 充分表征和有价值的DPPOS队列，并收集结果的测量结果， 在协议中描述。我们将1）进行新的分析，以表征异质性 病程及其长期并发症和确定易感性的因素，或 对糖尿病及其并发症和常见慢性衰老疾病的抵抗力，以及2） 探索与受试者保留、方案依从性和 完成测量，并确定是否可以实施替代方法， 改进保留和遵守情况，并扩大数据收集。这些目标将提供 对糖尿病前期和糖尿病及其长期结果的重要见解， DPPOS队列的潜在进一步研究。

Abnormal regulation of glycemia (“dysglycemia”) has a very long time course, from the earliest stage of pre-diabetes, to the onset of Type 2 diabetes (T2D), to the development of clinically detectable microvascular changes and measurable atherosclerosis, to clinically manifest complications with attendant morbidity and mortality. The Diabetes Prevention Program (DPP) focused on the pre-diabetes stage of dysglycemia and demonstrated powerful beneficial effects of lifestyle intervention (ILS) and metformin (MET), compared with placebo (PLBO), in preventing or delaying the onset of T2D over a 3-year period in a high-risk population (n=3234). The DPP also investigated and described the interventions, phenotypic and genotypic risk factors associated with T2D development, the effects of the interventions in the setting of these risk factors, the health economic implications of T2D prevention, and other outcomes of interest. Based on these results, the DPP lifestyle program has been widely implemented. The DPP Outcomes Study (DPPOS) has explored the longer-term effects of T2D prevention in the DPP cohort, bridging the period between pre-diabetes and T2D, and has examined outcomes that required more time to develop than the 3-years of DPP. DPPOS showed longer-term salutary effects of the original interventions on T2D prevention and on cardiovascular disease (CVD) risk factors. The risk for microvascular disease was significantly greater in subjects who developed T2D and increased with longer duration and higher hemoglobin A1c (HbA1c). There were no significant differences by treatment group in the prevalence of the aggregate microvascular outcome; however, compared with PLBO and MET, ILS significantly reduced the risk of microvascular disease among women and those with HbA1c ≥6.5%. During the one-year extension of DPPOS Phase 3, we will maintain and continue to follow the well-characterized and valuable DPPOS cohort, and collect measurements of outcomes as described in the protocol. We will 1) perform new analyses to characterize the heterogeneous course of dysglycemia and its long-term complications and factors that define susceptibility or resistance to diabetes, its complications, and common chronic conditions of aging, and 2) explore the factors associated with participant retention, adherence to the protocol and completion of measurements, and determine if alternative methods can be implemented to improve retention and adherence and to expand data collection. These aims will provide important insights into prediabetes and diabetes and their long-term outcomes and could serve the potential further study of the DPPOS cohort.