Should Doctors Screen All Kids for Type 1 Diabetes?

Millions worldwide live with type 1 diabetes, and for most the diagnosis came as a shock, following mysterious symptoms such as thirst and weight loss. But diabetes specialists have long known that certain blood tests can foretell the disease years earlier. That has left the field wrestling with a difficult question: Should healthy children get these blood tests, and would knowing about incipient diabetes help them?

Now, as a first wave of studies indicates such testing can prevent life-threatening complications at diagnosis, and with a new treatment to delay disease onset, the answers are tipping toward “yes.” Mass screening studies are expanding throughout North America and Europe, and in September 2023, Italy became the first country to pass a law that aims to make screening, via finger-prick blood tests, available to all children. At a meeting in Florence last week, the Juvenile Diabetes Research Foundation (JDRF) presented draft recommendations on caring for those who test positive.

Mass screening is “a totally different way of thinking about type 1 diabetes,” says Emily Sims, a pediatric endocrinologist at the Indiana University School of Medicine. It relies not on signs of diabetes itself, such as high blood sugar, but on something of a crystal ball: autoantibodies in the blood that signal immune attacks on insulin-secreting cells in the pancreas. Once a child falls ill with full-blown diabetes, and typically needs insulin replacement therapy, those cells are mostly destroyed. In general, nearly 45% of children with at least two types of these autoantibodies develop full-blown diabetes within 5 years, and nearly 100% will get it in their lifetime.

A child gets blood testing for autoantibodies as part of a population screening program in Colorado. Credit: AUTOIMMUNITY SCREENING FOR KIDS

There is currently no way to prevent type 1 diabetes. But recent studies suggest screening can help avert a life-threatening condition called diabetic ketoacidosis (DKA), which strikes when insulin levels fall perilously low and the body, unable to metabolize sugar, starts to break down fat for energy. Anywhere from 20% to 70% of children have DKA at the time they’re diagnosed; they’re typically admitted to the pediatric intensive care unit (PICU), sometimes with brain swelling, shock, and loss of consciousness. “Last week I had three kids come in on a Friday, all with DKA, all in the PICU,” says Kurt Griffin, a pediatric endocrinologist at Sanford Health. “We have to do better.”

Griffin adds that with a positive autoantibody test, doctors can track a child’s progression, monitoring symptoms and glucose levels to catch a drop in insulin early and head off DKA. JDRF’s draft guidance—crafted with input from dozens of outside experts— suggests that a confirmed positive test should be followed by periodic medical monitoring for disease progression and symptoms, says Anastasia Albanese-O’Neill, JDRF’s associate vice president of community screening.

One project, in Germany, screened tens of thousands of children and tracked those who tested positive. It found that among 118 who progressed to full-blown diabetes, the rate of DKA was just 2.5%. In Colorado, a similar project recorded a DKA rate of about 4%, less than one-tenth of the usual prevalence there, says Marian Rewers, the project leader and a pediatric endocrinologist at the University of Colorado’s Barbara Davis Center for Diabetes.

And now, for the first time, a drug can delay the onset of full-blown diabetes. In November 2022, the United States approved teplizumab, which is given intravenously for 2 weeks to people with autoantibodies and abnormal glucose levels and on average forestalls the disease by 2 to 3 years. It’s now under review by European drug authorities. Trials of other preventive treatments are underway. The potential to delay disease onset greatly strengthens the case for screening, says Emanuele Bosi, an endocrinologist at Vita-Salute San Raffaele University who helped craft the new Italian law.

Rachel Besser, a pediatric diabetologist at the University of Oxford, sees upsides to mass screening but cautions that it may take a psychological toll on those who test positive. She asks: “Do people want this knowledge hanging over their head” that they or their child will likely get full-blown diabetes in some number of years? The German mass screening study, called Fr1da, revealed parents’ anxiety after a positive test but showed it abated over time. And screening may also have psychological benefits, Besser and others note. It can potentially ease the trauma of a sudden diabetes diagnosis, which brings what Sims calls a “firehose information overload” on how to manage a life-changing disease. Besser is now setting up a registry of people in the U.K. who have tested positive for autoantibodies to learn from their experience.

She’s also co-leading one arm of a new $24 million screening effort called EDENT1FI. It will screen 200,000 young people across seven European countries and explore issues such as when and how often to screen. “A kid who is negative at 6 can become positive at 10” for autoantibodies, says Chantal Mathieu, an endocrinologist at University Hospital Leuven who’s leading the effort. But cost, logistics, and national preferences limit how often tests can be repeated.

Rewers’s group is partnering with clinics in the Denver area to screen children just before kindergarten—because, he says, “if you have one shot” that’s the best age to test. His team is also experimenting with bundling autoantibody testing into one of two already-recommended blood tests for kids— lead testing in toddlers and cholesterol testing in older children. Many efforts, including Rewers’s, combine autoantibody and celiac disease screening in the same blood test.

Whether money saved in health care costs by mass screening exceeds its price tag is another question mark. Only about 0.3% of children will test positive. Griffin launched a screening study in 2020 called PLEDGE, which so far includes 8500 children across five states; currently costs are about $35 per test. He hopes that as screening expands, costs will drop to $10 or even lower. “That goes a long way to making it doable.”

Mass screening “stands or falls” on the willingness of families to agree to it, says Jurgen Vercauteren, who leads a patient advisory committee being established for EDENT1FI. “It’s upsetting” for children to submit to a finger-prick blood test, he notes, and “we have to take that into account” in deciding how often to screen. He has type 1 diabetes and had his three children screened for autoantibodies. (All were negative.)

Besser, who also has type 1 diabetes, says that whether to embrace screening could come down to “an individual question” for each family: “Is it worth it?”

Source: https://www.science.org/content/article/should-doctors-screen-all-kids-type-1-diabetes