Saturday, September 18th, 2021

Could mass screening benefit kids at high risk of diabetes?

Children with type 1 diabetes must aggressively monitor their blood sugar.


Long before type 1 diabetes is diagnosed in patients, who sometimes show up at the hospital so sick they need to be admitted to intensive care, it has taken a silent toll: The immune system has mounted stealth attacks on insulinmaking cells in the pancreas. Scientists are now weighing whether to routinely screen children for those hidden attacks, which could spot youngsters at risk years before symptoms surge.

At the moment, there is no way to prevent the disease. But screening trials suggest finding high-risk children can avert severe illness at diagnosis. Identifying those likely to develop diabetes could also accelerate the testing of preventive therapies.

Still, screening across populations carries caveats. “Is this plausible” on a grand scale, asks Anette-Gabriele Ziegler, director of the Institute of Diabetes Research at Helmholtz Zentrum Munich. Cost effectiveness is also critical, and “different in every country,” she says.

At least one in 300 children in many countries develops type 1 diabetes by age 18. The disease calls for constant blood sugar monitoring and can cause complications including heart disease. Past studies have tested family members of affected people for several different autoantibodies in the blood that provide an early warning of the immune assault. The screening works: Studies show that each year, about 10% of children with two or more autoantibodies will develop diabetes, and after 15 years, about 85% have the disease.

But just 10% of people diagnosed have affected relatives. With growing hope that treatments to stave off disease are possible, screening efforts are now stretching to thousands of children with no family history. In January, Ziegler’s team reported results in JAMA from the first mass screening effort, after enlisting hundreds of paediatricians to collect blood from finger pricks of 90,000 2- to 5-year-olds in Bavaria . Similar efforts are underway in northwestern Germany and Colorado.

In medicine, it is unusual to screen for disease risk without a prevention strategy. The paradox, some say, is that without mass screening to find at-risk people, preventives are harder to test. “We need the screening to develop these therapies. We cannot do the one without the other,” Ziegler says.

A case in point was the first successful trial to delay diabetes, published last year. Screening to identify participants was limited to people with a family history, and it took more than 6 years to find the 76 enrollees. The trial reported that the experimental drug teplizumab, a monoclonal antibody that blunts immune activity, pushed back disease by about 2 years. That finding “changes the thinking” around prevention, says Olga Kordonouri, who specializes in pediatric diabetes at Children’s Hospital in Hanover, Germany, and is leading a screening study in Lower Saxony.

Ziegler’s study suggested mass screening could also avert a complication of the disease: a dangerous condition called diabetic ketoacidosis (DKA). DKA occurs when lack of insulin prompts the body to break down fat for fuel, resulting in high blood levels of compounds called ketones. Marked by vomiting, shortness of breath, and confusion, DKA can be life threatening and is associated with longer term difficulties in controlling blood sugar. In Europe, about 20% of children have DKA upon diagnosis of type 1 diabetes, and in the United States, about 40%.

Because the 280 children identified as high risk in Ziegler’s study were referred to specialists and their families were educated about diabetes, just two children developed DKA—out of 43 who progressed to diabetes over 2.5 years.

Marian Rewers, executive director of the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine, is leading the screening trial in Colorado. So far, his study has tested nearly 25,000 children, with results similar to Ziegler’s: two DKA cases among the 22 children who have developed diabetes.

Although those numbers are hopeful, some say screening for all would be premature. One concern is that finding a child has autoantibodies “doesn’t absolutely guarantee you’re going to have diabetes,” says David Nathan, director of the diabetes center at Massachusetts General Hospital. He’s curious whether screening studies that continue to follow participants can find ways to better refine who is at highest risk.

And even though Rewers and Ziegler have found physicians and families eager to participate, “There is a high bar to adding anything to the routine screening in any country,” Rewers says. Some screening proponents are trying to think practically. In the United States, many toddlers get a blood test for lead levels, so diabetes screening could be bundled in, says Jessica Dunne, director of the prevention program at JDRF, which helps fund and advise some screening projects. Rewers’s study combines diabetes screening with a test for an autoantibody that appears in celiac disease, in which the body can’t tolerate gluten. The study led by Kordonouri includes a cholesterol test, which in young children can indicate the genetic condition familial hypercholesteremia.

Ziegler is now studying the cost effectiveness of mass screening in Germany and trying to define the best age to screen. Australia and Israel are weighing mass screening. Different health systems and the results of the studies now running will play into the decisions, but Rewers is optimistic. “Support,” he says, “is snowballing.”

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