Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes Biostatistics Research Center (U01 Clinical Trial Not Allowed) | RFA DK 21 003

Opportunity Information: Apply for RFA DK 21 003

The NIH funding opportunity RFA-DK-21-003, titled "Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes - Biostatistics Research Center (U01 Clinical Trial Not Allowed)," supports the creation of a dedicated Biostatistics Research Center that will serve as the analytics and data coordination backbone for a larger NIH clinical research consortium focused on youth-onset type 2 diabetes (T2D). The award mechanism is a U01 cooperative agreement, which means the project is expected to be carried out in close collaboration with NIH program staff and alongside other consortium components rather than operating as a fully independent investigator-initiated grant. Although the work directly supports a major, longitudinal human cohort effort, the FOA is explicitly marked "Clinical Trial Not Allowed," signaling that the Biostatistics Research Center is not being funded to run an intervention study; instead, it is being funded to provide the statistical, data management, and methodological leadership needed to make the consortium's observational and mechanistic research rigorous, reproducible, and clinically meaningful.

This Biostatistics Research Center is designed to partner with Clinical Centers that are funded under a separate companion announcement (RFA-DK-21-002). Those Clinical Centers are responsible for recruiting and following a cohort of early pubertal youth who are at elevated risk for developing type 2 diabetes and then studying them prospectively through puberty, a developmental window that is strongly linked to changes in insulin sensitivity, beta cell stress, weight trajectory, and metabolic risk. In practical terms, the biostatistics component is meant to ensure that the consortium can turn complex, multi-site, multi-timepoint clinical and physiologic measurements into clear evidence about who progresses from risk states (such as prediabetes) to overt T2D, when that progression happens, and what measurable factors are most predictive of it. The emphasis on puberty underscores the scientific premise that this life stage may be a key inflection point for the onset and acceleration of metabolic disease in youth, and that understanding trajectories during this period is essential for better prevention and treatment strategies.

The consortium has two overarching scientific goals, and the Biostatistics Research Center is central to both. First, the consortium aims to sharpen risk prediction by developing more precise ways to identify which young people are truly on a path toward youth-onset T2D, rather than relying on broad, imperfect risk categories. That includes identifying determinants of progression from prediabetes to T2D, which could involve clinical measures, laboratory biomarkers, physiologic testing, demographics, family history, social or environmental factors, and patterns of change over time. The long-term intent is not prediction for its own sake, but prediction that is good enough to enable targeted prevention strategies that can later be tested efficiently in the right subgroups. Second, the consortium aims to deepen understanding of the physiologic drivers of youth-onset T2D, with particular attention to mechanisms relevant to achieving glycemic control and preserving pancreatic beta cell function. Since beta cell decline and failure are central features of T2D progression and treatment response, the ability to model beta cell trajectories and relate them to puberty-related physiologic change is a key methodological challenge that a specialized biostatistics center is expected to address.

From an operational and methodological standpoint, this FOA is about building a hub that can harmonize data across multiple clinical sites, support consistent analytic approaches, and ensure that study inferences are valid despite the realities of multi-center longitudinal research (such as missing data, varying follow-up times, measurement differences, and evolving protocols). While the text provided does not list detailed task requirements, the typical expectations for a consortium biostatistics and data coordination center under a U01 structure include leadership on study design elements, power and sample size considerations, statistical analysis plans, data standards, quality control procedures, reproducible workflows, and advanced modeling needed for prediction and mechanistic inference. Because the cohort spans puberty and likely captures repeated measures of metabolic, hormonal, and clinical phenotypes, the biostatistics center would be expected to bring expertise in longitudinal modeling, trajectory analysis, risk modeling, and potentially integrative methods for handling high-dimensional or multi-omic data if such data are collected by the consortium.

In terms of eligibility, the opportunity is broadly open to a wide range of U.S.-based organizations, including state, county, and local governments; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits (with or without 501(c)(3) status); for-profit organizations (including small businesses); independent school districts; special district governments; public housing authorities/Indian housing authorities; and federally recognized tribal governments as well as certain tribal organizations that are not federally recognized. The FOA also explicitly highlights inclusion of a range of mission- and community-focused institutions and organizations, such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, and U.S. territories or possessions. At the same time, it clearly restricts foreign involvement: non-U.S. entities and foreign institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by NIH policy are not allowed.

Administratively, the sponsoring agency is the National Institutes of Health, and the program sits within the health and nutrition research space (CFDA 93.847). The original closing date listed is March 3, 2022, the funding instrument is a cooperative agreement, and the award ceiling is stated as $25,000,000. The FOA was created on July 14, 2021. Taken together, the scale and structure signal a major, centrally coordinated NIH effort where the Biostatistics Research Center is expected to function as a core consortium resource, enabling the Clinical Centers' recruitment and longitudinal follow-up to translate into high-quality evidence about risk, progression, and physiology in youth-onset type 2 diabetes.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes Biostatistics Research Center (U01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2021-07-14.
• Applicants must submit their applications by 2022-03-03. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $25,000,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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