Advancing Type 1 Diabetes Research
Sanford Health is offering general population screening for type 1 diabetes and celiac autoantibodies through the PLEDGE study (Population Level Estimate of type 1 Diabetes risk Genes in children). The central innovation in PLEDGE is the integration into routine pediatric care across all Sanford clinics. This will enable measurement of costs and cost savings, to support inclusion of these tests in standard pediatric screening recommendations. Sanford Health is seeking to enroll ~ 20,000 children by 2025. Sanford patients under 6 years or between 9-16 years of age are eligible.
Type 1 Diabetes Research
Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta cells that produce insulin. At the centennial of insulin’s discovery, this drug remains the mainstay of treatment, while physicians still lack anything to address the underlying immune causes of T1D. A majority of children who develop T1D present at a late stage with diabetic ketoacidosis (DKA), resulting in increased costs of necessary intensive care, potentially worse glycemic control and cognitive deficits compared to those who were able to start insulin earlier and avoid DKA.
Hyperglycemia typically comes after a long period of autoimmunity, providing a window of opportunity to identify children at high risk of progressing to overt diabetes. Early identification and family awareness can enable ongoing monitoring and appropriate testing so that insulin can be started early enough to prevent serious illness. Such an approach has been shown in the ASK study to reduce the rate of DKA at presentation from 60% to 3%. In the long term, identifying these high-risk children will enable trials of prevention therapies. In the meantime, there are significant benefits to preventing DKA at presentation.
To date, it has been challenging to screen beyond immediate family members of people with T1D. Programs to offer screening more widely – such as the TEDDY, Fr1da and ASK studies – have relied on clinical research staff to recruit children from clinics, an approach that is difficult to scale up. For eventual acceptance into standard primary care, any population-based screening tool must be simple, reliable, cost-effective and easily implemented when children are present for routine visits.
The Screening Process
A blood spot for a SNP-based genetic risk score (GRS) is taken at study entry. For children enrolled prenatally, the GRS can be collected simultaneously with routine newborn screening samples. Autoantibodies for T1D are collected at routine clinic appointments at approximately between 2 and 5 years of age, or once between 9 and 16 years of age. At the latter screenings, celiac antibodies are also collected, the inclusion of which has shown increased family engagement in other T1D screening programs. Children identified to have T1D autoantibodies will be offered ongoing education, monitoring, and enrollment in appropriate intervention trials.
Critical to the success of this project is the innovative use of the electronic health record and associated patient messaging tools. Sanford Health has leveraged these platforms to automate invitations to participate, enable documentation of consent, collect assessments of parental worry, enter orders, and return results. Children with presymptomatic type 1 diabetes (multiple autoantibodies) are flagged for easy recognition to encourage appropriate testing in case they present for care with T1D symptoms.
As part of this project, economic modeling will be performed to assess costs and savings related to this screening approach. We will use real-world data from our health system and insurance plan to determine economic impacts.
This project is generously supported by Sanford Health and the Leona M. and Harry B. Helmsley Charitable Trust, with screening assays performed in collaboration with William Hagopian, MD, PhD, from the Pacific Northwest Research Institute and Richard Oram, PhD, from the University of Exeter and the Royal Devon and Exeter Hospital.
Request information about enrolling a child through My Sanford Chart.
For research-related questions about the Sanford PLEDGE study, email Kurt Griffin, PhD, MD.
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Sanford PLEDGE Study Patient Information
Children who are Sanford Health patients and are ages 0-5 or 9-16 years old or have a sibling with T1D or T1D antibodies may qualify for the PLEDGE study.
Our Commitment to End Type 1 Diabetes
The PLEDGE study is part of our mission to end type 1 diabetes. Learn more about our key research areas.