In the era of precision medicine, diabetes patients do not always fall neatly into diagnostic categories. A pioneering research network is tackling the gray area beyond type 1 (T1D) and type 2 (T2D) diabetes to better characterize atypical presentations.
The Rare and Atypical Diabetes Network (RADIANT) spans 15 clinical centers and two genetic core facilities from across the U.S. Principal investigators include Andrea Ramirez, M.D., an assistant professor in the Division of Diabetes, Endocrinology, and Metabolism at Vanderbilt University Medical Center.
“With so many forms, atypical diabetes can be a diagnostic challenge for providers. RADIANT provides a platform to share data so we can develop more precise testing and treatment strategies,” Ramirez said.
RADIANT centers around a study designed to build a database of clinical, genetic, metabolomic and laboratory data from people with rare and atypical diabetes. The data will fuel research into both diagnostics and targeted therapeutics.
“With so many forms, atypical diabetes can be a diagnostic challenge for providers.”
Participants include those already enrolled in existing diabetes and disease registries, who will be retrospectively recruited, plus prospective referrals. No ages are specifically excluded.
The RADIANT team will investigate all suspected atypical cases to rule out those with known forms of diabetes. Those participants will not provide additional biologic samples and will instead serve as a comparison population.
The remaining referrals, who do not fit in existing diagnostic categories, will undergo further testing including whole genome sequencing. The RADIANT team also plans to study affected family members. Through this process, RADIANT will build a rich resource for researchers. The study could help characterize previously unknown types of diabetes.
Fostering Research Collaboration
A major goal of RADIANT is to foster data sharing. Qualified collaborators around the country may access methods, technologies, data, and even biologic samples through the RADIANT Data Coordinating Center. RADIANT is also submitting data to the NIDDK Central Repository. The RADIANT team is encouraging investigators to submit ancillary studies for consideration.
Data sharing is key to uncovering the etiologic basis of atypical diabetes, said Kevin Niswender, M.D., an associate professor of medicine, molecular physiology, and biophysics at Vanderbilt. Niswender is collaborating with researchers in the Vanderbilt Diabetes Research and Training Center to analyze RADIANT data.
“RADIANT provides a platform to share data so we can develop more precise testing and treatment strategies.”
“Research into atypical diabetes is currently quite limited, and study numbers are small,” Niswender said. “We’re aggregating existing data, and collecting new samples — all to phenotype and genotype perhaps the least understood forms of diabetes, which has not been done previously.”
Understudied and Misdiagnosed
The researchers say RADIANT will lay a foundation to uncover novel pathways that can lead to diabetes. Long-term, the study may help patients with rare and atypical diabetes avoid a more generalized diagnosis. Studies suggest atypical diabetes affects up to 8 percent of people who receive a T1D or T2D diagnosis. Ramirez says these misdiagnoses can delay or lead to inappropriate treatment.
“Currently, patients with atypical diabetes are seen throughout the country, but in an uncoordinated way. This makes it challenging for providers to identify effective therapeutics.”
The researchers emphasize the heterogeneity in diabetes development and presentation. Understudied subtypes like latent autoimmune diabetes in adults, Wolfram syndrome, neonatal diabetes and Ketosis-Prone diabetes are now recognized. RADIANT provides a path to detailing a far greater range of disease, Ramirez said.