UroEDIC Bladder: Bladder Dysfunction in Type 1 Diabetes

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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.