NIDDK director Griffin Rodgers and Judith Fradkin, NIDDK’s director of the Division of Diabetes, Endocrinology and Metabolic Diseases responded to questions by Endocrine News about future opportunities and challenges in diabetes research.
EN: What are the opportunities and challenges in diabetes research?
The prevalence, costs, and human burden associated with diabetes create both opportunities and challenges for diabetes research. Research is needed to address the particularly troubling emergence of type 2 diabetes and rising rates of both type 2 diabetes and type 1 diabetes in youth. In addition to eye, nerve, kidney, and heart complications, diabetes substantially increases risk for dementia, cancer, and other major concomitants of aging.
NIDDK is collaborating across the National Institutes of Health (NIH) in research to understand and develop therapies to mitigate these risks. Prioritizing across the many unanswered questions about prevention and management of diabetes and its complications is a challenge. Also challenging is translating into practice hugely successful NIDDK-supported research studies such as the Diabetes Prevention Program and Diabetes Control and Complications Trial, and diminishing the disproportionate burden of diabetes in disadvantaged populations. Novel therapies for diabetes and the new Precision Medicine Initiative® create an opportunity to determine which therapy is best for a specific individual. Central to all forms of diabetes are exciting opportunities to regenerate or replace beta cells.
New therapeutic approaches are anticipated through major investments in brain and gut regulation of appetite and metabolism; beta cell biology; brown and beige fat; and tissue crosstalk mediated by hormones, myokines, adipokines, and incretins.
EN: The Special Diabetes Program (SDP) is up for reauthorization next year. How has the SDP helped improve research and treatment over the past two years?
Early SDP funding contributed to the development of the first FDA-approved hybrid closed-loop device, and current funding is supporting phase 3 artificial pancreas (AP) trials and development of next generation AP components. The Environmental Determinants of Diabetes in the Young (TEDDY) Study has begun applying ‘omics’ technologies to 2.7 million biosamples from an observational study of over 8,000 newborns at high genetic risk yielding hundreds of children with autoimmunity or type 1 diabetes. This case-control analysis will be the largest study of microbiome development in children and is poised to identify environmental triggers of type 1 diabetes.
In 2015, the Endocrine Society, the American Diabetes Association (ADA), and JDRF adopted a new staging approach for presymptomatic type 1 diabetes based on data from TEDDY, TrialNet, and other SDP-supported studies. TrialNet is near completion of three major randomized trials testing prevention strategies for type 1 diabetes with results expected in 2017 and 2018. The Human Islet Research Network (HIRN) is progressing toward producing and protecting new beta cells; finding markers of silent beta cell loss; identifying beta cell heterogeneity; and creating an “islet on a chip” with multiple islet cell types constituted from human pluripotent stem cells housed in 3-D niches. These tools will help researchers understand how beta cell function is lost in diabetes and test new approaches to slow progression of the disease or replace lost beta cells.
EN: What are some of the exciting diabetes-related research that NIDDK is working on right now?
Major NIDDK clinical trials include: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a head-to-head comparison of four commonly used drugs in combination with metformin; Restoring Insulin Secretion study (RISE), testing whether early aggressive therapy of type 2 diabetes will slow or reverse beta cell loss; Vitamin D and Type 2 Diabetes study (D2d), testing vitamin D’s efficacy in type 2 diabetes prevention; the Diabetes Prevention Program Outcomes Study (DPPOS), phase 3 studying the effect of metformin on cardiovascular disease and cancer; and Preventing Early Renal Function Loss in Diabetes (PERL) trial, which is studying allopurinol for diabetic nephropathy.
The prevalence, costs, and human burden associated with diabetes create both opportunities and challenges for diabetes research.
New therapeutic approaches are anticipated through major investments in brain and gut regulation of appetite and metabolism; beta cell biology; brown and beige fat; and tissue crosstalk mediated by hormones, myokines, adipokines, and incretins.
EN: What NIDDK-supported resources should scientists be aware of to help advance diabetes research?
The AMP Type 2 Diabetes Knowledge Portal enables browsing, searching, and analysis of human genetic information linked to type 2 diabetes and related traits from more than 100,000 DNA samples. The National Mouse Metabolic Phenotyping Centers (MMPC) provide experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice. The NIDDK Central Repository provides access to data and biospecimens from NIDDK-funded clinical studies. The NIDDK Information Network (dkNET) enables researchers to search for resources such as mouse strains, antibodies, or data sets. Finally, the Integrated Islet Distribution Program (IIDP) distributes high quality human islets.
Links to these and other resources are at www.niddk.nih.gov/research-funding/research-resources.
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