RADIANT: Rare and Atypical Diabetes Network

University of South Florida (Other)
Overall Status
CT.gov ID
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Study Details

Study Description

Brief Summary

RADIANT is a network of 14 clinical sites and several laboratories dedicated to the study of atypical diabetes.

The objective of this study is to define new forms of diabetes and the unique mechanisms underlying these forms of atypical diabetes. The specific aims are to:

  1. Identify and enroll individuals and families with undiagnosed rare and atypical forms of diabetes.

  2. Determine the etiologic basis of the metabolic disorder among individuals and families with novel forms of rare and atypical diabetes.

  3. Understand the pathophysiology of individuals and families with novel forms of rare and atypical forms of diabetes.

Detailed Description

RADIANT has three distinct stages.

Stage 1:

Stage 1 participants will complete a consent form and a questionnaire to determine the potential for having atypical forms of diabetes. Participants identified as potentially atypical based on questionnaire responses will be asked to provide a blood sample to test for islet autoantibodies and complete additional questionnaires.

The RADIANT Adjudication Committee, which is comprised of a team of experts in diabetes, will assess the data collected in Stage 1 and select and prioritize participants to proceed to Stage 2 and 3 for Whole Genome Sequencing (WGS) and other testing.

Stage 2:

Stage 2 of the study includes genetic screening for known forms of monogenic diabetes. Participants will consent for this stage of the study, complete a family history questionnaire, and have blood collected for DNA and RNA extraction, storage, and analysis. WGS will be performed on all DNA samples. If no pathogenic/likely pathogenic variant in a known monogenic diabetes gene that is thought to explain the participant's diabetes is identified by WGS, RNA Sequencing will be performed at Baylor College of Medicine.

Stage 3:

Stage 3 of the study includes deeper phenotyping. All participants who proceed to Stage 3 will visit a study clinic to consent and complete Stage 3 Standard procedures which include: an Oral Glucose Tolerance Test (OGTT), additional blood collection, a detailed physical exam, and additional questionnaires.

Discovery Team Review:

The work of the Discovery Team is expected to be an iterative process analyzing all data collected up to this point in the study to understand the significance of novel variants. In some instances, the Discovery Team may determine that enrollment of the Proband's family members is necessary. Family members with suspected atypical diabetes will follow the same study procedures as described above. Affected and unaffected family members may also be enrolled for Sanger Sequencing. The Discovery Team may also recommend additional optional procedures to better characterize the participant's form of diabetes.

Study Design

Study Type:
Anticipated Enrollment :
2000 participants
Observational Model:
Time Perspective:
Official Title:
Rare and Atypical Diabetes Network
Actual Study Start Date :
Sep 30, 2020
Anticipated Primary Completion Date :
Sep 1, 2030
Anticipated Study Completion Date :
Sep 1, 2030

Outcome Measures

Primary Outcome Measures

  1. Phenotypic and genotypic characterization of previously unknown forms of diabetes using Whole Genome Sequencing (WGS), and deeper phenotyping methods [Through study completion, an average of 3 years.]

    Deeper phenotyping methods include both clinical and laboratory assessments. Clinical data includes anthropometric and biometric data, medical histories, and standard questionnaires (ASA24, PROMIS, environmental exposures depression and anxiety). Laboratory data includes WGS, transcriptomics, metabolomics, mitochondrial sequencing, Oral Glucose Tolerance Test (OGTT), and Islet autoantibodies. Clustering methods will be used to define cohorts of similar diabetes genotypes and phenotypes based on this data.

Eligibility Criteria


Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:

The following criteria or phenotypes will be considered for suspecting "atypical" participants:

  • Type 2 diabetes diagnosed at a time when the individual was prepubertal or non-obese

  • Mendelian pattern, especially with early onset (<18 years old)

  • Syndromic (multiple systems involved)

  • Lipodystrophic

  • Extremes of BMI

  • "Mitochondrial" characteristics (e.g., myopathy, hearing deficits)

  • Non-progressive

  • Rapidly progressive ("fulminant")

  • Low insulin requirements (<0.5 u/kg/day)

  • Cyclical hyperglycemia with periods of remission

  • Lean persons with polycystic ovarian syndrome (PCOS)

  • History of gestational diabetes (GDM) when lean

  • Lean insulin-resistant persons

  • If islet autoantibodies and beta-cell function parameters have been measured (where "A" = islet cell autoantibodies, "B" = beta-cell function):

oA-B- (i.e., lacking islet autoimmunity makers and lacking beta cell function) oA-B+ with unprovoked DKA at initial presentation (i.e., lacking islet autoimmune markers, with preserved beta-cell function, but presenting with unprovoked DKA) oA-B+ of very young onset (pre-pubertal) (i.e., lacking islet autoimmune markers, with preserved beta-cell function, but very early onset T2D-like phenotype)

Exclusion Criteria:
  • Those with high likelihood of typical type 1, typical type 2, known monogenic, or other known secondary forms of diabetes

  • Refusal of consent for genetic testing

  • Islet autoantibody positive (participants who are islet autoantibody positive but present with additional atypical features i.e. syndromic, strong linear family history of diabetes may not be excluded)

  • Women who are currently pregnant

Contacts and Locations


Site City State Country Postal Code
1 University of Colorado- Denver Aurora Colorado United States 80045
2 University of Chicago Chicago Illinois United States 60637
3 Indiana University Indianapolis Indiana United States 46202
4 University of Maryland Baltimore Maryland United States 21201
5 Massachusetts General Hospital (MGH) Boston Massachusetts United States 02114
6 University of Michigan Ann Arbor Michigan United States 48109
7 Washington University in St. Louis Saint Louis Missouri United States 63110
8 SUNY Downstate Health Sciences University Brooklyn New York United States 11203
9 Columbia University New York New York United States 10032
10 University of North Carolina at Chapel Hill Chapel Hill North Carolina United States 27514
11 Vanderbilt University Nashville Tennessee United States 37232
12 Baylor College of Medicine Houston Texas United States 77030
13 Seattle Children's Seattle Washington United States 98105
14 University of Washington Seattle Washington United States 98109

Sponsors and Collaborators

  • University of South Florida
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


  • Study Chair: Jeffrey Krischer, PhD, University of South Florida

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
University of South Florida
ClinicalTrials.gov Identifier:
Other Study ID Numbers:
  • 5U54DK118638
  • 5U54DK118612
First Posted:
Sep 16, 2022
Last Update Posted:
Sep 16, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by University of South Florida
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 16, 2022