PLEDGE Pediatric Screening Study

Advancing Type 1 Diabetes Research

Sanford Health has implemented a type 1 diabetes screening program using routine well child visits. To demonstrate the feasibility and develop evidence to support eventual inclusion in standard primary care, we have initiated the PLEDGE study (Population Level Estimate of type 1 Diabetes risk Genes in children). Sanford Health is seeking to screen 33,000 children over four years (2020 to 2024), focusing on children under 6 years of age.

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.

The onset of hyperglycemia 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 the prevention of 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 into the study, 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 present for routine visits.

The Screening Process

A blood spot for a SNP-based genetic risk score is taken at study entry, which can be collected as early as the usual newborn screening samples. Autoantibodies for T1D are collected at approximately age 2 and 5 years of age at well child clinic appointments. At the latter screening, antibodies relevant to celiac disease will also be collected. This addition has been shown to increase family engagement and participation in other T1D screening programs. Children identified to have T1D autoantibodies will be offered ongoing monitoring and enrollment in appropriate intervention trials.

Critical to the success of this project is the innovative use of the electronic medical 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.

Timeline of PLEDGE Study Clinic Visits

0-60 Days Old

Newborn Screening
Blood spot
Genetic risk score for type 1 diabetes and celiac disease

2 Years Old

24-Month Well-Child Visit
Blood sample
Type 1 diabetes autoantibodies

4-6 Years Old

Pre-K Well-Child Visit
Blood sample
Type 1 diabetes and celiac disease autoantibodies

As part of this project, Sanford Research’s population health group will develop a dynamic economic model to assess costs and savings related to this screening approach. We will then 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.

For research-related questions about the Sanford PLEDGE study, email Kurt Griffin, MD.

Request information about enrolling a child through My Sanford Chart.