DPPOS Follow-Up

 描述(由申请人提供)：血糖调节异常(“血糖异常”)有一个非常长的过程，从其最早的阶段，标记为糖尿病前期，到2型糖尿病(T2D)的发病，发展到临床可检测到的微血管变化和可测量的动脉粥样硬化，到临床表现出并发症并伴随着发病率和死亡率。糖尿病预防计划(DPP)侧重于糖尿病前期的血糖紊乱，与安慰剂相比，生活方式干预(ILS)和二甲双胍(MET)在预防或推迟高危人群(n=3234)3年内糖尿病发病方面显示出强大的有益效果。DPP还描述了与糖尿病发展相关的表型和遗传型风险因素的作用、影响干预成功的因素以及糖尿病预防的健康经济影响。在这些成果的基础上，民进党生活方式计划得到了广泛的实施。DPP结果研究(DPPOS)探索了T2D预防的长期效果，跨越了糖尿病前期和T2D之间的11年随访期，以检查比相对较短的DPP 3年(n=2776)需要更多时间才能发展的结果。DPPOS显示了原始干预在T2D预防和心血管疾病(CVD)危险因素方面的长期有益效果。使用MET可节省成本，使用ILS可节约成本。尽管任何一种积极干预都没有显著降低总的微血管结局，但预防T2D的患者与发生T2D的患者相比，发生微血管并发症的风险降低了28%。并发症的风险与T2D持续时间和HbA1c水平有关。拟议的项目(DPPOS后续行动)将利用长期随机暴露于MET和密集表型和基因分型的DPPOS队列(n=2776)，对DPPOS队列进行10多年的研究，包括约1500名已知T2D持续时间的患者和约1200名尚未发展为T2D的患者，以解决关于长期暴露于MET和ILS的尚未回答的问题，这些患者在血糖异常的早期就开始了。DPPOS后续行动将检查在患有糖尿病前期和T2D的老龄化人口中日益引起公共健康关注的结果，包括心血管疾病、癌症和伴随的生活质量的发展。DPPOS随访的首要目标是有效检查：1)在糖尿病前期早期开始应用二甲双胍治疗对心血管疾病和癌症的风险可能带来的好处；2)ILS和T2D预防措施对糖尿病进一步发展的长期疗效，以及对传统的和新近发现的血糖异常并发症的影响；3)基于分类诊断(糖尿病前期与糖尿病)和连续序列的现代临床病程，包括仔细分析与DPP干预措施的相互作用以及已确定的和新的风险因素。

 DESCRIPTION (provided by applicant): Abnormal regulation of glycemia ("dysglycemia") has an extremely long time course, from its earliest stage, labeled pre-diabetes, to the onset of Type 2 diabetes (T2D), 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, in preventing or delaying the onset of diabetes mellitus over a 3-year period in a high- risk population (n=3234). The DPP also described the role of phenotypic and genotypic risk factors associated with diabetes development, the factors that influenced the success of the interventions and health economic implications of diabetes prevention. On the basis of these results, the DPP lifestyle program has been widely implemented. The DPP Outcomes Study (DPPOS) explored the longer-term effects of T2D prevention, bridging the period between pre-diabetes and T2D over 11 years of follow-up, to examine outcomes that required more time to develop than the relatively brief 3 years of DPP (n=2776). DPPOS showed longer-term salutary effects of the original interventions on T2D prevention and on cardiovascular disease (CVD) risk factors. Prevention was cost-saving with MET and cost-effective with ILS. Although the aggregate microvascular outcome was not significantly reduced by either active intervention, those in whom T2D was prevented had a 28% lower risk of developing microvascular complications compared with those who developed T2D. The risk of complications was associated with T2D duration and HbA1c levels. The proposed project (DPPOS Follow-up), will study the DPPOS cohort for 10 more years, taking advantage of the long-term randomized exposure to MET and the densely phenotyped and genotyped DPPOS cohort (n=2776), including ~1500 patients with known T2D duration and ~1200 who have not developed T2D, to address yet unanswered questions about long-term exposure to MET and ILS initiated early in the course of dysglycemia. DPPOS Follow-up will examine outcomes that are of increasing public health concern in an aging population with pre-diabetes and T2D, including the development of CVD, cancer, and concomitant quality of life. The overarching goals of DPPOS Follow-up are to examine efficiently: 1) the putative benefits of metformin therapy begun early in the prediabetic phase on risk for CVD and cancer; 2) the very long-term effects of T2D prevention with ILS and MET by intention-to-treat on further development of diabetes, and on traditional and more recently recognized complications of dysglycemia; and 3) the modern day clinical course of dysglycemia and its associated complications, based on both categorical diagnoses (pre-diabetes vs. diabetes) as well as a continuum, including a careful analysis of interactions with DPP interventions as well as established and novel risk factors.