DPPOS Followup

DPPOS跟进

• 批准号: 8852388
• 负责人: Elizabeth Mary Venditti
• 金额: $ 28.23万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-15 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8852388
• 关键词: Address; Adult; Affect; Age; Atherosclerosis; Biochemical; Blood Vessels; Cardiovascular Diseases; Caring; Clinical; Complications of Diabetes Mellitus; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Disease Outcome; Effectiveness; Enrollment; Epidemiology; Evaluation; Event; Exposure to; Genotype; Glucose; Glycosylated hemoglobin A; Goals; Individual; Intention; Intervention; Label; Life Style; Living Costs; Long-Term Effects; Longitudinal Studies; Malignant Neoplasms; Measurable; Medicine; Metabolic; Metformin; Methods; Microvascular Dysfunction; Minority; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Study; Participant; Patients; Pharmaceutical Preparations; Phase; Phenotype; Physical Function; Placebos; Population; Prediabetes syndrome; Prevalence; Prevention; Public Health; Quality of life; Randomized; Regulation; Reporting; Risk; Risk Factors; Role; Safety; Specific qualifier value; Staging; Time; adjudicate; age effect; age related; aging population; base; cardiovascular disorder risk; clinically relevant; cognitive function; cohort; comparative effectiveness; cost; cost effective; diabetes prevention program; diabetic; economic impact; economic implication; effective intervention; follow-up; health economics; high risk; human disease; intervention effect; lifestyle intervention; mortality; novel; prevent; programs; public health relevance; success; treatment strategy

 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.

 描述（由申请人提供）：糖尿病的异常调节（“糖尿病障碍”）具有极长的时间过程，从其最早阶段（标记为前驱糖尿病）到2型糖尿病（T2 D）的发作、临床上可检测的微血管变化和可测量的动脉粥样硬化的发展，到临床上表现出并发症以及伴随的发病率和死亡率。糖尿病预防项目（DPP）关注糖尿病前期的精神障碍，并在高危人群（n=3234）中证实了与安慰剂相比，生活方式干预（ILS）和二甲双胍（MET）在3年内预防或延迟糖尿病发作方面的强大有益作用。DPP还描述了与糖尿病发展相关的表型和基因型风险因素的作用，影响干预措施成功的因素以及糖尿病预防的卫生经济影响。在这些成果的基础上，民进党的生活方式方案得到了广泛实施。DPP结局研究（DPPOS）探索了T2 D预防的长期影响，在11年的随访期间桥接糖尿病前期和T2 D之间的时期，以检查比相对较短的3年DPP（n=2776）需要更多时间才能形成的结局。DPPOS显示了原始干预措施对T2 D预防和心血管疾病（CVD）风险因素的长期有益影响。MET的预防是节省成本的，ILS的预防是具有成本效益的。尽管两种主动干预均未显著降低总体微血管结局，但与发生T2 D的患者相比，预防T2 D的患者发生微血管并发症的风险降低了28%。并发症风险与T2 D持续时间和HbA 1c水平相关。 拟建项目（DPPOS随访），将对DPPOS队列进行10年以上的研究，利用长期随机暴露于MET和密集表型和基因型DPPOS队列（n=2776），包括约1500例已知T2 D病程的患者和约1200例未发生T2 D的患者，以解决尚未回答的问题，长期暴露于MET和ILS开始在病程早期的障碍。DPPOS随访将检查在糖尿病前期和T2 D老龄化人群中日益增加的公共卫生问题的结果，包括CVD，癌症和伴随的生活质量的发展。DPPOS随访的总体目标是有效地检查：1）在糖尿病前期早期开始二甲双胍治疗对CVD和癌症风险的推定获益; 2）通过意向治疗使用ILS和MET预防T2 D对糖尿病进一步发展以及对传统和最近认识到的功能障碍并发症的长期影响;和3）现代糖尿病及其相关并发症的临床过程，基于分类诊断（糖尿病前期与糖尿病）以及连续体，包括对与DPP干预的相互作用以及已确定的和新的风险因素的仔细分析。