22/22 Diabetes Prevention Program Outcomes Study (DPPOS) Phase 3 - Biostatistics Center

22/22 糖尿病预防计划成果研究 (DPPOS) 第 3 阶段 - 生物统计中心

• 批准号: 9052497
• 负责人: Michael Dean Larsen
• 金额: $ 400.36万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 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/9052497
• 关键词: Address; Adult; Affect; Age; Atherosclerosis; Biochemical; Biometry; Blood Vessels; Cardiovascular Diseases; Caring; Cessation of life; Clinical; Cognitive; Complications of Diabetes Mellitus; Data; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Effectiveness; Epidemiology; Event; Exposure to; Functional disorder; Genetic; Genotype; Glucose; Glycosylated hemoglobin A; Goals; Hypotension; Incidence; Individual; Intention; Intervention; Label; Life Style; Lipids; Living Costs; 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; Phase; Phenotype; Physical Function; Placebos; Population; Prediabetes syndrome; Prevalence; Prevention; Prevention program; Public Health; Quality of life; Randomized; Randomized Clinical Trials; Regulation; Reporting; Risk; Risk Factors; Skin Carcinoma; Specific qualifier value; Staging; Stroke; Time; Universities; Washington; Woman; adjudicate; age effect; age related; aging population; base; blood pressure reduction; cardiovascular disorder risk; clinically relevant; cognitive function; cohort; comparative effectiveness; cost; cost effective; diabetes prevention program; diabetic; economic impact; economic implication; follow-up; health economics; high risk; human disease; insight; interest; intervention effect; lifestyle intervention; mortality; novel; prevent; programs; public health relevance; response; 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）：血糖异常调节（“血糖异常”）有一个很长的时间过程，从最早的阶段（标记为糖尿病前期）到2型糖尿病（T2D）的发作，到临床可检测到的微血管变化和可测量的动脉粥样硬化的发展，到临床上表现出的并发症以及随之而来的发病率和死亡率。糖尿病预防计划 (DPP) 重点关注糖尿病前期的血糖异常，并证明生活方式干预 (ILS) 和二甲双胍 (MET) 与安慰剂 (PLBO) 相比，在三年内预防或延缓高危人群 (n=3234) 的 T2D 发病方面具有强大的有益作用。 DPP 还调查并描述了干预措施、与 T2D 发展相关的表型和基因型风险因素、干预措施对这些风险因素的影响、T2D 预防的健康经济影响以及其他感兴趣的结果。基于这些结果，民进党的生活方式计划已得到广泛实施。为期 11 年的后续 DPP 结果研究 (DPPOS) 探讨了 T2D 预防的长期影响，弥合了糖尿病前期和 T2D 之间的时期，并检查了与相对较短的 3 年 DPP 相比需要更多时间才能形成的结果。 DPPOS 显示出原始干预措施对 T2D 预防和心血管疾病 (CVD) 危险因素的长期有益效果。 MET 的预防可以节省成本，而 ILS 的预防则具有成本效益。总体而言，患有 T2D 的受试者发生微血管疾病的风险明显更高，并且随着持续时间的延长和糖化血红蛋白 (A1C) 的升高而增加。治疗组的总体微血管结局发生率没有显着差异；然而，与 PLBO 和 MET 相比，ILS 显着降低了女性和研究结束时 A1C ≥ 6.5% 的女性患微血管疾病的风险。 拟议的 DPPOS 第 3 期将对 DPPOS 队列进行 10 年以上的研究，利用长期随机暴露于 MET 以及密集表型和基因分型的 DPPOS 队列（n=2778），其中包括近 1600 名已知 T2D 病程的患者和约 1200 名未发展为 T2D 的患者，以解决有关糖尿病前期期间开始的长期暴露于 MET 和 ILS 的尚未解答的问题。 DPPOS 第 3 阶段将研究对患有糖尿病前期和 T2D 的老龄化人群日益引起公众健康关注的结果，包括 MET 对 CVD 和癌症发展的假定益处。 DPPOS 3 期的主要目标是有效检查：1）糖尿病前期开始的二甲双胍治疗对风险的长期影响 用于心血管疾病和癌症； 2) ILS 和 MET 意向治疗对 T2D 进一步发展以及传统和最近认识的血糖异常并发症的长期影响及其经济影响； 3) 血糖异常的临床病程，通过分类诊断（糖尿病前期与糖尿病）作为一个连续体进行评估，及其与并发症发生的关系，包括分析与 DPP 干预措施的相互作用以及已确定的和新的危险因素。