UroEDIC Bladder: Bladder Dysfunction in Type 1 Diabetes

项目摘要 糖尿病控制和并发症试验（DCCT）及其观察性随访糖尿病流行病学 干预和并发症（EDIC）是糖尿病研究的里程碑式成就。DCCT 在一项随机试验中，1441名1型糖尿病（T1 D）男性和女性患者参加了强化与常规治疗的比较， 胰岛素治疗，延缓糖尿病并发症的发生和进展， 全世界的病人管理。实施严格的血糖控制降低了 T1 D的毁灭性并发症，如早期死亡，失明和截肢。男性和女性T1 D患者 面临新的挑战，包括认知能力下降、自主神经功能障碍和泌尿系统疾病。UroEDIC， 在DCCT/EDIC队列中检查泌尿系统并发症的辅助研究，结合25年 详细的医疗信息和>90%的参与泌尿系统症状评估每年 自2010年以来，它是T1 D患者最长时间的最广泛的泌尿学评估。 上一个资助周期将下尿路症状（LUTS）和尿失禁（UI）确定为 T1 D男性和女性中患病率最高且对质量影响最大的泌尿系统疾病 生活质量（QOL）。通过将强大的纵向泌尿表型与广泛的临床和实验室数据联系起来， 通过DCCT/EDIC，我们可以大大加深我们对糖尿病相关泌尿系统并发症的理解。 初步分析表明，虽然许多患者发展为LUTS或UI的固定状态，但许多其他患者在治疗过程中发生了变化。 进出这个州我们的总体假设是代谢、自主神经和上皮细胞 功能障碍与男性和女性持续和可逆的LUTS和UI亚表型相关 患有糖尿病观察结果还表明，在这一队列中，两种性别的膀胱过度活动都在增加。 然而，对其他糖尿病膀胱问题的负担和影响缺乏了解， 特别是糖尿病性膀胱病，其典型地被描述为膀胱感觉降低、收缩性差和 残余尿量高。因此，UroEDIC膀胱的目标是：1）表征全谱 2）创建解释LUTS/UI进展和缓解的风险模型， 和3）确定这些症状持续存在的机制性主题。的具体目标 该项目旨在纳入新提出的和可用的膀胱纵向数据 保留，自主神经功能障碍和新的转录签名与全方位的 DCCT/EDIC测量，以深入了解纵向模式和机制， LUTS/UI和全面表征T1 D中的糖尿病膀胱功能障碍。

PROJECT SUMMARY The Diabetes Control and Complication Trial (DCCT) and its observational follow up Epidemiology of Diabetes Intervention and Complications (EDIC) represent landmark achievements in diabetes research. The DCCT enrolled 1441 men and women with type 1 diabetes (T1D) in a randomized trial of intensive vs. conventional insulin therapy, delaying the onset and progression of diabetic complications and dramatically changing the management of patients worldwide. Implementation of tight glycemic control has reduced the frequency of devastating complications of T1D such as early death, blindness and amputation. Women and men with T1D face new challenges including cognitive decline, autonomic dysfunction and urological disorders. UroEDIC, an ancillary study examining urological complications in the DCCT/EDIC cohort, combines over 25 years of detailed medical information and >90% participation in urological symptom assessment annually since 2010, making it the longest running most extensive urological evaluation of persons with T1D. The previous funding cycle identified lower urinary tract symptoms (LUTS) and urinary incontinence (UI) as urological disorders in men and women with T1D with the highest prevalence and greatest impact on quality of life (QOL). By linking powerful longitudinal urological phenotypes with extensive clinical and laboratory data of the DCCT/EDIC, we can substantially deepen our understanding of diabetes associated urinary complications. Preliminary analyses show that although many patients develop a fixed state of LUTS or UI, many others move in and out of the state over time. Our overall hypothesis is that metabolic, autonomic and epithelial dysfunctions are associated with persistent and reversible subphenotypes of LUTS and UI in men and women with diabetes. Observations also indicate bladder overactivity in both genders is increasing in this cohort. However, there is a lack of understanding of the burden and impact of other diabetic bladder problems, particularly diabetic cystopathy, classically described as decreased bladder sensation, poor contractility and high residual urine volume. The goals of UroEDIC Bladder, therefore, are to 1) characterize the full spectrum of bladder dysfunction in T1D, 2) create risk models that explain the progression and remission of LUTS/UI, and 3) identify mechanistic themes underpinning the persistence of these symptoms. The specific aims of this project are designed to incorporate newly proposed and available longitudinal data on bladder retention, autonomic dysfunction and novel transcriptional signatures with the full range of DCCT/EDIC measurements to gain deeper insight into the longitudinal patterns and mechanisms of LUTS/UI and comprehensively characterize diabetic bladder dysfunction in T1D.