Project Grant R01DK148455

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The General Hospital Corporation (Massachusetts General Hospital) $990,000 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to conduct a pilot study testing whether polygenic architecture can inform targeted screening and treatment strategies for type 1 and type 2 diabetes.

The research implements a genetics-first, recall-by-genotype framework embedded in the Mass General Brigham health system. In Aim 1, researchers will use a multi-ancestry type 1 diabetes polygenic score and screen 150 adults in the top 2.5% of genetic risk for islet autoantibodies (GAD65, IA-2, ZNT8, and insulin). Participants with one positive antibody will complete an oral glucose tolerance test to assess glycemia and candidacy for preventive immunotherapy, with results returned to participants and clinicians via standardized pathway. The study will quantify clinical features marking autoimmunity and estimate numbers-needed-to-screen across alternative polygenic thresholds. In Aim 2, researchers will recruit 100 adults—25 per high-risk polygenic score category (B-cell dysfunction, obesity, lipodystrophy-like phenotypes) and 25 controls from the interquartile range—to complete baseline physiologic phenotyping via liquid mixed-meal tolerance testing and other pathway-specific challenges.

The award leverages the MGB biobank linked with electronic health records (>65,000 genotyped individuals). Work is performed in Boston, Massachusetts, with a period of performance from September 1, 2026, through August 31, 2029.