The National Institutes of Health (NIH) invites applications for the NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01), focusing on high-risk, multi-center observational studies relevant to diabetes, digestive, kidney, and related diseases. This funding opportunity (PAR-25-089), reissued as a cooperative agreement, supports hypothesis-driven research conducted at multiple clinical centers, emphasizing participation from diverse populations, including underserved communities. Notably, the process involves two phases: a planning phase (U34) to prepare for recruitment and a subsequent clinical study phase (U01). Essential components include a Plan for Enhancing Diverse Perspectives (PEDP) to improve inclusivity within research teams. Key dates include a submission opening on January 3, 2025, and funding restricted to high-risk studies, excluding low-risk clinical trials. Eligible applicants range from higher education institutions to for-profit organizations, though foreign entities are ineligible to apply directly. Applications should detail the study design, community engagement, and a comprehensive budget, with an emphasis on quality control and data management. Successful proposals will demonstrate significant societal impact, innovation, and a robust approach to participant diversity, aligned with NIDDK’s health equity goals.