Limited Competition for the Continuation of Epidemiology of Diabetes Interventions and Complications (EDIC) Study Clinical Research Center (Collaborative U01)

项目摘要 糖尿病控制和并发症试验(DCCT，1983-1993)比较强化治疗的目的是 1441例1型患者的接近正常血糖与无特定血糖靶点的常规治疗的比较 糖尿病(T1 DM)的平均随访时间为6.5年。强化治疗降低了视网膜病变的风险， 肾病和神经病变的发病率分别为35%-76%，高血糖是并发症的主要决定因素。我们 还描述了强化治疗的潜在不良影响；评估了其对心血管疾病的影响 (心血管疾病)风险因素、神经认知和生活质量；并预测终生健康--经济影响。DCCT 强化治疗随后在世界范围内被采纳为T1 DM的标准护理。 《糖尿病干预及其并发症的流行病学》(EDIC，1994-至今)是 对DCCT队列的观察性随访研究，94%的幸存者积极参与。 参与者每年接受一次评估。心血管疾病事件和死亡事件被仔细记录和裁决。EDIC 值得注意的是，强化治疗与常规治疗相比，对并发症的早期益处 已经持续了15年以上，尽管在EDIC期间两组的HbA1c水平相似，称为 新陈代谢记忆。以前的强化治疗也大大降低了心血管事件的风险，高级 微血管并发症，如慢性肾脏疾病和需要手术的眼睛并发症；以及 死亡率。DCCT/EDIC合作者还用单独的资金进行了许多辅助研究。 未来5年(2017-22)的总体目标将是利用忠诚度和高度 确定DCCT/EDIC队列的特征，并研究身体和认知功能障碍的发生等 老年1型糖尿病人群中的晚期并发症及其危险因素。自即日起 糖尿病治疗延长了1型糖尿病患者的寿命，关键是要了解 衰老对1型糖尿病患者的影响及确定发生衰老敏感的危险因素 赤字。此外，长期严重并发症的累积将使研究其风险因素和 生活质量和健康的经济后果。 具体的科学目标是：1)检查认知、情感和身体疾病的流行程度 T1 DM的损害，以及DCCT治疗组、血糖、已确诊和推定的相关性 关于衰老重要领域的非血糖风险因素：认知、情感和身体损害， 功能受限、残疾、生活质量、虚弱、跌倒、骨折和生存；2)分析风险 与严重/晚期微血管并发症相关的因素/机制；3)风险分析 与心血管疾病和死亡率相关的因素/机制；4)开发新的研究方法来衡量 从独特的长期、纵向随访中得出的T1 DM患者糖尿病结局(载体)的进展 以及5)研究T1 DM的长期经济后果。

Project Summary The Diabetes Control and Complications Trial (DCCT, 1983-1993) compared intensive therapy aimed at near normal glycemia versus conventional therapy with no specific glucose targets in 1441 subjects with type 1 diabetes (T1DM) over a mean follow-up of 6.5 yrs. Intensive therapy reduced the risks of retinopathy, nephropathy, and neuropathy by 35-76%, hyperglycemia being a primary determinant of complications. We also described potential adverse effects of intensive therapy; assessed its effects on cardiovascular disease (CVD) risk factors, neurocognition and quality of life; and projected the lifetime health-economic impact. DCCT intensive therapy was then adopted world-wide as standard-of-care for T1DM. The Epidemiology of Diabetes Interventions and its Complications (EDIC, 1994-present) is the observational follow-up study of the DCCT cohort, with 94% of those surviving actively participating. Participants are evaluated annually. CVD events and deaths are carefully documented and adjudicated. EDIC has notably shown that the early beneficial effects of intensive versus conventional therapy on complications have persisted for more than 15 years despite the similar HbA1c levels in the two groups during EDIC, termed metabolic memory. Former intensive therapy also greatly reduced the risk of CVD events, advanced microvascular complications, such as chronic kidney disease and eye complications requiring surgery, and mortality. DCCT/EDIC collaborators have also conducted numerous ancillary studies with separate funding. The overarching goals for the next 5 years (2017-22) will be to take advantage of the loyal and highly characterized DCCT/EDIC cohort and study the occurrence of physical and cognitive dysfunction and more advanced complications, and their risk factors, in this aging type 1 diabetes population. Since current-day diabetes therapy has increased the longevity of people with type 1 diabetes, it is critical to understand how aging affects patients with type 1 diabetes and to define the risk factors for the occurrence of aging sensitive deficits. In addition, the accrual of long-term severe complications will allow the study of their risk factors and the quality-of-life and health economic consequences. The specific scientific aims are to 1) examine the prevalence of cognitive, affective, and physical impairments in T1DM, and the association of DCCT treatment arm, glycemia, and established and putative non-glycemic risk factors on important domains of aging: cognitive, affective and physical impairments, functional limitations, disability, quality-of-life, frailty, falls, fractures, and survival; 2) analyze the risk factors/mechanisms associated with severe/advanced microvascular complications; 3) analyze the risk factors/mechanisms associated with CVD and mortality; 4) develop new research approaches to measure the progression of diabetes outcomes (vectors) in T1DM, derived from the unique long-term, longitudinal follow-up of the DCCT cohort; and 5) study the long-term economic consequences of T1DM.