10/22 Diabetes Prevention Program Outcomes Study (DPPOS) Phase 3- Research Project

10/22 糖尿病预防计划成果研究 (DPPOS) 第 3 阶段 - 研究项目

• 批准号: 9883792
• 负责人: Amisha Wallia
• 金额: $ 34.16万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-20 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883792
• 关键词: Address; Affect; Aftercare; Age; Atherosclerosis; Biochemical; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Categories; Cessation of life; Clinical; Cognitive; Cohort Studies; Complications of Diabetes Mellitus; Cost Savings; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Effectiveness; Epidemiology; Event; Exposure to; Functional disorder; Genetic; Genotype; Glucose; Glycosylated hemoglobin A; Goals; Incidence; Individual; Intention; Intervention; Intervention Studies; Label; Life Style; Lipids; Long-Term Effects; Longitudinal Studies; Malignant Neoplasms; Measurable; Medicine; Metabolic; Metformin; Methods; Microvascular Dysfunction; Morbidity - disease rate; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Study; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phenotype; Physical Function; Placebos; Prediabetes syndrome; Prevalence; Prevention; Public Health; Quality of life; Randomized; Randomized Clinical Trials; Regulation; Reporting; Research Project Grants; Risk; Risk Factors; Specific qualifier value; Stroke; Time; Woman; adjudicate; adult obesity; age effect; age related; aging population; base; cardiovascular disorder risk; cardiovascular risk factor; care costs; clinical development; clinically relevant; cognitive function; cohort; comparative effectiveness; cost; cost effective; diabetes prevention program; economic evaluation; economic impact; economic implication; effective intervention; follow-up; group intervention; health economics; high risk; high risk population; human disease; insight; interest; intervention effect; intervention program; lifestyle intervention; mortality; novel; phase 3 study; prevent; programs; public health relevance; risk variant; treatment group

 DESCRIPTION (provided by applicant): Abnormal regulation of glycemia ("dysglycemia") has a very long time course, from its earliest stage, labeled 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 11-year follow-up DPP Outcomes Study (DPPOS) explored the longer-term effects of T2D prevention, bridging the period between pre-diabetes and T2D, and examined outcomes that required more time to develop than the relatively brief 3-years of DPP. 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. Overall, the risk for microvascular disease was significantly greater in subjects who developed T2D and increased with longer duration and higher hemoglobin A1c (A1C). 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 who had A1C ≥6.5% at study end. The proposed DPPOS Phase 3 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=2778), which includes nearly 1600 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 during pre-diabetes. DPPOS Phase 3 will examine outcomes that are of increasing public health concern in the aging population with pre-diabetes and T2D, including the putative benefits of MET on development of CVD and cancer. The main goals of DPPOS Phase 3 are to examine efficiently: 1) the long-term effects of metformin therapy begun in the pre-diabetic phase on risk for CVD and cancer; 2) the long-term effects by intention-to-treat of ILS and MET on further development of T2D and on traditional and more recently recognized complications of dysglycemia, and of their economic impact; and 3) the clinical course of dysglycemia, evaluated by categorical diagnoses (pre-diabetes vs diabetes) and as a continuum, and their associations with the development of complications, including analyses of interactions with DPP interventions and 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”）具有非常长的时间过程，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，到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。糖尿病预防计划（DPP）关注糖尿病前期的糖尿病性精神障碍，并证明了生活方式干预（ILS）和二甲双胍（MET）与安慰剂（PLBO）相比在预防或延迟高危人群（n=3234）3年内T2 D发作方面的强大有益作用。DPP还调查并描述了与T2 D发展相关的干预措施、表型和基因型风险因素、干预措施在这些风险因素背景下的影响、T2 D预防的健康经济影响以及其他关注的结局。基于这些结果，DPP生活方式方案得到了广泛实施。11年随访DPP结局研究（DPPOS）探讨了T2 D预防的长期影响，桥接糖尿病前期和T2 D之间的时期，并检查了比相对较短的3年DPP需要更多时间才能发展的结局。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。总体而言，发生T2 D的受试者发生微血管疾病的风险显著更高，并且随着病程延长和血红蛋白A1 c（A1 C）升高而增加。不同治疗组的总体微血管结局患病率无显着差异;然而，与PLBO和MET相比，ILS显着降低了女性和研究结束时A1 C ≥6.5%的女性患微血管疾病的风险。 拟定的DPPOS III期研究将对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=2778），其中包括近1600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开始在糖尿病前期。DPPOS第3阶段将检查在糖尿病前期和T2 D老年人群中日益增加的公共卫生问题的结果，包括MET对CVD和癌症发展的推定益处。DPPOS III期的主要目标是有效地检查：1）在糖尿病前期开始二甲双胍治疗对CVD和癌症风险的长期影响; 2）ILS和MET意向治疗对T2 D进一步发展以及对传统和最近认识到的精神障碍并发症的长期影响，以及其经济影响;和3）通过分类诊断（糖尿病前期vs糖尿病）和作为一个连续体评估的精神障碍的临床病程，及其与并发症发生的相关性，包括与DPP干预措施的相互作用分析以及已确定的和新的风险因素。