UroEDIC is an Ancillary Study that seeks to advance our understanding of common urological complications of type 1 diabetes by taking advantage of the extensive longitudinal data of the Epidemiology of Diabetes Intervention and Complication (EDIC), a major ongoing NIDDK research study. UroEDIC protocols for phenotyping urological symptoms, including erectile dysfunction (ED) in men and urinary incontinence (UI) in women, have allowed us to develop risk factor models and assess the impact of these complications on health related quality of life. We are poised to substantially deepen our understanding of diabetes associated ED and UI by applying novel high throughput discovery approaches to the powerful longitudinal urological phenotypes and extensive clinical and laboratory data of the parent study. Preliminary analyses using repeated measures show that although many patients develop a fixed state of ED or UI, an equal number move in and out of the state over time. Our overall hypothesis is that genomic, metabolic, and psychological factors contribute to persistent and reversible subphenotypes of ED and UI. The specific aims of this project are: 1. Characterize the longitudinal annualized patterns of ED and UI in men and women with T1D. 2 Identify novel candidates for mechanisms associated with diabetic ED and UI by linking existing serum biochemistry and genotypes to new measures of gene methylation and expression. 3. Examine the bidirectional relationship between health related QOL and longitudinal patterns of ED and UI in men and women with T1D. This proposal is highly responsive to PAR 12-265 Ancillary Studies to Major Ongoing Clinical Research Studies by expanding on extensive longitudinal clinical data, high quality phenotypes, and adding new genomic and informatics expertise to a multidisciplinary team of experienced UroEDIC and EDIC investigators. While we have already learned a great deal from this cohort, completion of this proposal will contribute critical data to expand our understanding of the natural history, mechanisms and sequelae of the most impactful urologic complications associated with T1D. It also sets the stage for future work such as development of organ-specific conceptual models of ED and UI; prevention/intervention studies for urological complications of T1D; validation of biological and quantitative models in other diabetic populations; and development of a clinically relevant tool (risk calculator) to quantify individual risk in T1D.