The Rare and Atypical Diabetes Network (RADIANT) Study: Design and Early Results
Authors:   RADIANT Study Group, Balasubramanyam Ashok , Redondo Maria J. , Craigen William , Dai Hongzheng , Davis Ansley , Desai Dimpi , Dussan Monica , Faruqi Jordana , Gaba Ruchi , Gonzalez Iliana , Jhangiani Shalini , Kubota-Mishra Elizabeth , Liu Pengfei , Murdock David , Posey Jennifer , Ram Nalini , Sabo Aniko , Sisley Stephanie , Tosur Mustafa , Venner Eric , Astudillo Marcela , Cardenas Adriana , Fang Mary Ann , Hattery Erica , Ideouzu Adrienne , Jimenez Julizza , Kikani Nupur , Montes Graciela , O’Brien Nikalina G. , Wong Lee-Jun , Goland Robin , Chung Wendy K. , Evans Anabel , Gandica Rachelle , Leibel Rudolph , Mofford Kaisha , Pring James , Evans-Molina Carmella , Anwar Farrah , Monaco Gabriela , Neyman Anna , Saeed Zeb , Sims Emily , Spall Maria , Hernandez-Perez Marimar , Mather Kieren , Moors Kelly , Udler Miriam S. , Florez Jose C. , Calverley Melissa , Chen Victoria , Chu Kathy , Cromer Sara , Deutsch Aaron , Faciebene Mariella , Greaux Evelyn , Koren Dorit , Kreienkamp Raymond , Larkin Mary , Marshall William , Ricevuto Pam , Sabean Amy , Thangthaeng Nopporn , Han Christopher , Sherwood Jordan , Billings Liana K. , Banerji Mary Ann , Bally Kylnt , Brown Necole , Ji Beisi , Soni Lina , Lee Melissa , Abrams Jennifer , Thomas Lorraine , Abrams Jennifer , Skiwiersky Samara , Philipson Louis H. , Greeley Siri Atma W. , Bell Graeme , Banogon Shanna , Desai Jui , Ehrmann David , Letourneau-Freiberg Lisa R. , Naylor Rochelle N. , Papciak Erin , Friedman Ross Lainie , Sundaresan Manu , Bender Colleen , Tian Persephone , Rasouli Neda , Kashkouli Mohsen Bahmani , Baker Chelsea , Her Andrew , King Courtney , Pyreddy Avinash , Singh Vatsala , Barklow Jules , Farhat Noosha , Lorch Rebecca , Odean Carter , Schleis Gregory , Underkofler Chantal , Pollin Toni I. , Bryan Hadley , Maloney Kristin , Miller Ryan , Newton Paula , Nikita Maria Eleni , Nwaba Devon , Silver Kristi , Tiner Jessica , Whitlatch Hilary , Palmer Kathleen , Riley Stephanie , Streeten Elizabeth , Oral Elif A. , Broome David , Dill Gomes Anabela , Foss de Freitas Maria , Gregg Brigid , Grigoryan Seda , Imam Salman , Sonmez Ince Melda , Neidert Adam , Richison Carman , Akinci Baris , Hench Rita , Buse John , Armstrong Chase , Christensen Chad , Diner Jamie , Fraser Rachael , Fulghum Karla , Ghorbani Tahereh , Kass Alex , Klein Klara , Kirkman M. Sue , Hirsch Irl B. , Baran Jesica , Dong Xiaofu , Kahn Steven E. , Khakpour Dori , Mandava Patali , Sameshima Lori , Kalerus Thanmai , Pihoker Catherine , Loots Beth , Santarelli Kathleen , Pascual Cisco , Niswender Kevin , Edwards Norma , Gregory Justin , Powers Alvin , Ramirez Andrea , Scott Jennifer , Smith Jordan , Urano Fumihiko , Hughes Jing , Hurst Stacy , McGill Janet , Stone Stephen , May Jennifer , Krischer Jeffrey P. , Adusumalli Rajesh , Albritton Bruce , Aquino Analia , Bransford Paul , Cadigan Nicholas , Gandolfo Laura , Garmeson Jennifer , Gomes Joseph , Gowing Robert , Karges Christina , Kirk Callyn , Muller Sarah , Morissette Jean , Parikh Hemang M. , Perez-Laras Francisco , Remedios Cassandra L. , Ruiz Pablo , Sulman Noah , Toth Michael , Wurmser Lili , Eberhard Christopher , Fiske Steven , Hutchinson Brandy , Nekkanti Sidhvi , Wood Rebecca , Florez Jose C. , Alkanaq Ahmed , Brandes MacKenzie , Burtt Nöel , Flannick Jason , Olorunfemi Phebe , Udler Miriam S. , Caulkins Lizz , Wasserfall Clive , Winter William , Pittman David , Akolkar Beena , Lee Christine , Carey David J. , Hood Daniel , Marcovina Santica M. , Newgard Christopher B. 
Published: April 2023

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.