PLEDGE Pediatric Screening Study

Pediatric screening for type 1 diabetes and celiac disease integrated into routine care

From 2020 to 2026, Sanford offered general population screening for type 1 diabetes and celiac disease autoantibodies through the PLEDGE (Population Level Estimate of Type 1 Diabetes Risk Genes in Children) study.

The central innovation in PLEDGE was the integration of study procedures into routine pediatric care across all Sanford Health clinics. In addition to assessing efficacy, this enabled measurement of costs and cost savings. These economic analyses are critical to support inclusion of these tests in standard pediatric screening recommendations.

Sanford Health enrolled nearly 20,000 children. Sanford Health patients under 6 years old or between 9 and 16 years of age were eligible.

Why screen for type 1 diabetes?

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta cells that produce insulin. At the centennial of insulin’s discovery, it remains the mainstay of treatment but does nothing to address autoimmunity.

Now, with the approval of teplizumab for Stage 2 T1D, we have access to the first drug targeting the autoimmunity causing T1D. Other drugs are currently in development, too.

However, for any interventions to be used, we need to identify who might benefit from these therapies.

Most children who develop T1D present at a late stage with diabetic ketoacidosis (DKA), necessitating hospitalization and intensive care. DKA at presentation is associated with worse long-term glycemic control and cognitive deficits compared to those who were able to start insulin earlier and avoid DKA. Preventing initial DKA can decrease long-term complications with associated morbidity, mortality and related healthcare costs.

Hyperglycemia develops after a long period of autoimmunity, providing a window of opportunity to identify children who have a higher risk of progressing to overt diabetes. Early identification and family awareness can enable ongoing monitoring and appropriate testing so that insulin and other treatments can be started early enough to prevent serious illness.

Such an approach has been shown in the ASK Research Program 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.

Why screen all children?

To date, it has been challenging to screen beyond immediate family members of people with T1D. However, 90% of people with T1D do not have a family history of the disease.

Programs that offer screening more widely – such as the TEDDY, Fr1da and ASK studies – have relied on clinical research staff to recruit children from clinics. This approach is costly and difficult to scale.

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

For PLEDGE, a blood spot for a targeted SNP-based genetic risk score (GRS) was taken at study entry. For children enrolled prenatally, this was collected simultaneously with routine newborn screening samples.

Anti-islet antibodies were collected at routine clinic appointments at about 2 years old and again at about 5, or once between 9 and 16 years of age. At the latter screenings, celiac antibodies were also collected, the inclusion of which has shown increased family engagement in other T1D screening programs.

Children who have a close family member with T1D were sometimes eligible for more frequent screening.

Critical to the success of this project was the innovative use of the electronic health record and its associated patient messaging tools. Sanford leveraged these platforms to automate invitations to participate, enable documentation of consent, administer participant surveys, enter orders and return results.

The success of PLEDGE relied on the existing infrastructure of Sanford’s integrated health system. Labs were collected at routine clinic visits and specimens were sent to hub laboratories and Sanford’s reference lab for batching, processing and shipping to Pacific Northwest Research Institute and CU Anschutz Barbara Davis Center for Diabetes.

As a part of this project, economic modeling was performed to assess costs and savings related to this screening approach. We used real-world data from our health system and insurance plan to determine economic impacts. This data was an important factor when considering T1D screening inclusion in recommendations for standard preventive care.

Children with T1D-related antibodies

Children identified to have persistent T1D autoantibodies were offered ongoing education, monitoring or enrollment in appropriate intervention trials.

Monitoring is tailored to the individual’s risk. Throughout the monitoring process, we maintain communication with the primary care team. The shared electronic health record is flagged for easy recognition of antibody-positive children to encourage appropriate testing in case they present for care with T1D symptoms. 

Sanford Pledge Sites

Our Partners
The PLEDGE study was generously supported by Sanford Health and the Leona M. and Harry B. Helmsley Charitable Trust. Collaborators include William Hagopian, MD, PhD, from the Pacific Northwest Research Institute; Richard Oram, PhD, from the University of Exeter and the Royal Devon and Exeter Hospital; and Marian Rewers, MD, PhD, from the CU Anschutz Barbara Davis Center for Diabetes.

For research-related questions about the Sanford PLEDGE study, email kurt.griffin@sanfordhealth.org to contact Kurt Griffin, PhD, MD.

If you would like to enroll your child in a T1D screening, please visit our screening page.