The Rare and Atypical Diabetes Network (RADIANT) Study: Design and Early Results

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.

Atypical Diabetes: What Have We Learned and What Does the Future Hold?

“…In this review, we seek to provide an overview of some of the characteristic features of well-described forms of atypical diabetes, including examples of those for which the etiological basis is known and others for which the etiological basis is not yet fully understood. Atypical diabetes is suspected in individuals who do not fit clearly into currently accepted criteria that define type 1 diabetes (T1D), type 2 diabetes (T2D), or secondary diabetes ( 1 , 2 ). We introduce the concept of endotypes, in which patients with diabetes can be clustered based on similar clinical or molecular/genetic mechanisms.…”

“…Currently, such a classification does not exist and the clinical utility of such data in diabetes care is limited. The Rare and Atypical Diabetes Network (RADIANT) exemplifies this approach and research focus needed to elucidate all forms of atypical diabetes, their clinical characteristics, and their molecular and pathophysiological etiologies ( 2 ). This work will inform implementation of omics tools for diagnostic and therapeutic purposes and enable a more complete cataloging and classification of atypical diabetes.…”

Investigator and participant expectations for returning non-genetic results: insights from the Rare and Atypical Diabetes Network (RADIANT) study

“…The Rare and Atypical DIAbetes NeTwork (RADIANT) is a network of academic health centers across the United States that aims to discover and define rare and atypical forms of diabetes [ 3 ]. RADIANT participants proceed through up to three study stages of data collection with eligibility re-determined at each stage based on likelihood that the participant’s diabetes is both atypical and novel as described elsewhere [ 4 ]. Genetic and non-genetic data (laboratory, clinical phenotyping, and questionnaires), and omics data are collected in different stages (Table 1 ).…”