The Rare and Atypical Diabetes Network (RADIANT) Study: Design and Early Results
RADIANT Study Group, Ashok Balasubramanyam, María J. Redondo, William Craigen, Hongzheng Dai, ANSLEY E. DAVIS, Dimpi Desai, Monica Dussan, Jordana Faruqi, Ruchi Gaba, Iliana Gonzalez, Shalini N. Jhangiani, Elizabeth Kubota-Mishra, Pengfei Liu, David R. Murdock, Jennifer E. Posey, Nalini Ram, Aniko Sabo, Stephanie Sisley, Mustafa Tosur, Eric Venner, Marcela Astudillo, Adriana Cardenas, Mary Ann Fang, E. Gonzalez Hattery, Adrienne Ideouzu, Julizza Jimenez, Nupur Kikani, Graciela Montes, Nikalina G. O’Brien, Lee‐Jun C. Wong, Robin Goland, Wendy K. Chung, Anabel Evans, Rachelle Gandica, Rudolph L. Leibel, Kaisha Mofford, James Pring, Carmella Evans‐Molina, Farrah Anwar, Gabriela Monaco, Anna Neyman, Zeb Saeed, Emily K. Sims, Maria Spall, Marimar Hernández‐Pérez, Kieren J. Mather, Kelly Moors, Miriam S. Udler, José C. Florez, MELISSA M. CALVERLEY, Victoria Chen, Kathy Chu, Sara J. Cromer, Aaron J. Deutsch, Mariella Faciebene, Evelyn Greaux, Dorit Koren, Raymond J. Kreienkamp, Mary Larkin, William Marshall, Pam Ricevuto, Amy Sabean, Nopporn Thangthaeng, Christopher Han, Jordan S. Sherwood, Liana K. Billings, Mary Ann Banerji, Kylnt Bally, N.M. Brown, Beisi Ji, Lina Soni, Melissa Lee, Jennifer Abrams, Lorraine Thomas, Jennifer Abrams, Samara Skiwiersky, Louis H. Philipson, Siri Atma W. Greeley, Graeme I. Bell, Shanna Banogon, Jui Desai, David A. Ehrmann, Lisa R. Letourneau, Rochelle N. Naylor, Erin Papciak, Lainie Friedman Ross, Manu Sundaresan, Colleen Bender, Persephone Tian, Neda Rasouli, Mohsen Bahmani Kashkouli, Chelsea Baker, Andrew Her, Courtney King, Avinash Pyreddy, Vatsala Singh, Jules Barklow, Noosha Farhat, R. Lorch
Abstract
OBJECTIVE: The Rare and Atypical Diabetes Network (RADIANT) will perform a study of individuals and, if deemed informative, a study of their family members with uncharacterized forms of diabetes. RESEARCH DESIGN AND METHODS: The protocol includes genomic (whole-genome [WGS], RNA, and mitochondrial sequencing), phenotypic (vital signs, biometric measurements, questionnaires, and photography), metabolomics, and metabolic assessments. RESULTS: Among 122 with WGS results of 878 enrolled individuals, a likely pathogenic variant in a known diabetes monogenic gene was found in 3 (2.5%), and six new monogenic variants have been identified in the SMAD5, PTPMT1, INS, NFKB1, IGF1R, and PAX6 genes. Frequent phenotypic clusters are lean type 2 diabetes, autoantibody-negative and insulin-deficient diabetes, lipodystrophic diabetes, and new forms of possible monogenic or oligogenic diabetes. CONCLUSIONS: The analyses will lead to improved means of atypical diabetes identification. Genetic sequencing can identify new variants, and metabolomics and transcriptomics analysis can identify novel mechanisms and biomarkers for atypical disease.