Pediatric endocrinologist Kurt J. Griffin, MD, PhD, has frequently seen children come to his clinic with diabetic ketoacidosis (DKA), a life-threatening condition caused by the body’s inability to regulate blood sugars.
Early intervention can reduce DKA rates to about 5% which improves long-term glycemic measures. Lower A1c levels are also associated with fewer long-term complications. But because type 1 diabetes (T1D) is difficult to diagnose early—and 92% of children don’t have a family history of the disease—many kids fall through the cracks.
“We've always had this notion that if we could catch it sooner, kids will do better,” said Dr. Griffin, research director for diabetes clinical trials at Sanford Research, part of Sanford Health.
At Sanford Health, more than 50% of children are diagnosed with type 1 diabetes only after developing DKA. To change this, the health system launched the Population Level Estimate of type 1 Diabetes risk Genes in Children (PLEDGE) study in 2020. The program screens children for type 1 diabetes antibodies and celiac disease to detect disease at earlier stages.
“Early identification allows us to monitor them more closely and provide treatment sooner to prevent DKA, improve long-term health and offer clinical trial opportunities that might slow the progression,” Sanford Research explained on its website.
As the largest rural health system in the U.S., Sanford Health serves more than 2 million patients across seven states in the upper Midwest. Its wide geographic footprint made it an ideal setting to test population-based screening. PLEDGE offers screening to all Sanford patients younger than 6 or between 9 and 16 years old and has already enrolled more than 13,000 children.
Sanford Health is part of the AMA Health System Member Program, which provides enterprise solutions to equip leadership, physicians and care teams with resources to help drive the future of medicine.
Early intervention is vital
Research has shown that a patient with two or more diabetes antibodies approaches 100% lifetime risk of needing insulin. Dr. Griffin believes type 1 diabetes should be recognized first as an autoimmune disease rather than only when high blood sugars appear.
Patients are considered at stage 1 if they have two or more antibodies but normal blood sugar, and stage 2 if blood sugar levels are already abnormal. Identifying children in these presymptomatic stages opens the door to early interventions, including a recently approved drug, teplizumab, which can delay progression to stage 3 diabetes.
“Our hope is that earlier recognition of T1D autoimmunity will enable more effective interventions,” Dr. Griffin said. With an episode of diabetic ketoacidosis, “you can measure an impact on the brain that accumulates. If we can avoid that in the first place, that's a win.”
A team effort
The PLEDGE study began as a small, hands-on effort in Sioux Falls, South Dakota.
“We learned a lot from that first clinic—about which parts were working smoothly and which parts were a little cumbersome to implement in a busy clinic,” said Dr. Griffin.
Physician engagement and patient buy-in were critical. Candice L. Nelson, MD, one of the first physician participants, said her team developed one- to two-minute explanation for families on why the study was important.
“The research team asked for our input right off the bat—what we thought was going to work well, how we could make it better,” said Dr. Nelson, co-chair for general pediatrics at Sanford Children's Hospital and chief of staff at Sanford USD Medical Center.
Today, patients in 192 different locations across the health system are participating in PLEDGE.
Harness the EHR
Despite covering a large and sparsely populated region, Sanford Health integrates all patients into one EHR. Each week, the system automatically identifies eligible children with upcoming appointments, and those parents receive an invitation message in the patient portal about enrolling in PLEDGE.
“This centralization enables implementation in a way that we don't need a coordinator sitting in each clinic: what would normally need hundreds of staff is being accomplished by three people,” said Dr. Griffin.
With the parent’s consent, the child’s blood is drawn during a regular visit at the clinic. Results are then posted to the patient portal, and families are contacted directly if antibodies are found. Patients with positive results are monitored like in a typical research study, with the EHR flagging care gaps and next test dates.
“It’s our obligation to keep an eye on them. If they do progress to where they need intervention, we catch it before they get sick,” Dr. Griffin said.
The study also screens for celiac disease, which often overlaps genetically with type 1 diabetes. So far, 80 patients are being monitored for diabetes antibodies and 81 have been referred to gastroenterology for celiac disease evaluation.
Several children who had vague symptoms didn't know they had celiac disease. Those patients are now on a gluten-free diet and their families “are really happy,” said Dr. Griffin.
The standard of care in physician well-being recognition
Institutions in this article have been honored by the Joy in Medicine® Health System Recognition Program.
Partner with primary care doctors
Dr. Griffin’s research team works closely with the primary care physicians since families often turn to their trusted doctor even after receiving results from PLEDGE.
Emails and messages through MyChart explain results and next steps, easing the burden on pediatricians, said Dr. Nelson. Sometimes the child is signed up for PLEDGE before the doctor even brings it up.
Education is key for families
The care teams ensure that parents know every step of the care plan if their child has a positive result.
“Will you as a parent be able to be proactive? Will you be able to watch out for all the signs and symptoms before your child gets sick?” said Dr. Nelson. These are the scenarios the team prepares them for.
Most families are “just so thankful that we empowered them to help prevent issues from developing,” she said, noting many participate in follow-up research or prevention trials.
Doctors see results
Already, several children identified through PLEDGE have progressed to higher blood sugar levels requiring clinical care—but none developed diabetic ketoacidosis. This is a striking difference from what Dr. Griffin is used to seeing in clinic, where patients often arrived critically ill and in need of intensive care.
PLEDGE has also gained momentum among physicians. When positive cases appear, signups increase at that clinic.
“The physician sees this has been a benefit and they start talking about it more with their patients,” said Dr. Griffin. If the doctor endorses it, that encourages the families to sign up. This is also true of the patients who undergo celiac disease testing.
He would eventually like to see PLEDGE evolve from a classic research study to a clinical program separate from research. And Dr. Nelson believes these types of screenings should also become a standard of care.
As a research study, there are no costs to participate in PLEDGE. It is not covered by insurance but since it is part of a research study, there is no cost for patients to participate. When T1D screenings become included in standards of care—such as American Academy of Pediatrics Bright Futures—the screenings would be covered by insurance. Until then, children screened outside of a research study may be responsible for the out-of-pocket costs, creating a barrier to care for many families.
“If we can make this the standard of care, to take the cost part out of the equation for families, I think that’s really important,” said Dr. Nelson.
The PLEDGE Study is supported by Sanford Health and the Leona M. and Harry B. Helmsley Charitable Trust.
