International guidance and new European data back type 1 diabetes screening for all children

Nearly two-thirds of children that were found to have early-stage type 1 diabetes through a screening program in eight European countries had no parent or sibling with the disease, researchers reported at the European Association for the Study of Diabetes (EASD) Annual Meeting in Milan earlier this month.

The data arrived weeks after an international panel published the first consensus guidance on screening the general population for early-stage type 1 diabetes in Diabetologia. The guidance calls for a first blood test for diabetes-related antibodies between ages 2 and 4. Children who test negative would be retested at ages 6 to 8 and again at ages 10 to 15.

Type 1 diabetes develops in stages. In stages 1 and 2, the immune system has started attacking insulin-producing cells, but the person has no symptoms. Stage 3 is clinical type 1 diabetes. Identifying people in the earlier stages has been associated with clinical benefits, including a lower risk of diabetic ketoacidosis (DKA) at diagnosis, according to EASD.

What the European type 1 diabetes screening program found

The screening was run by the EDENT1FI consortium, a European effort coordinated by Chantal Mathieu, M.D., Ph.D., of KU Leuven in Belgium, and Anette-Gabriele Ziegler, M.D., director of the Institute of Diabetes Research at Helmholtz Munich in Germany. Sites in the Czech Republic, Denmark, Germany, Italy, Poland, Portugal, Sweden and the U.K. used a common protocol. Children were screened with a finger-stick blood sample, and those with two or more antibodies had a second blood sample taken to confirm the result.

In all, 140,568 children and teens were screened. Their median age was 7.6 years. Among the 10,273 participants with a first-degree relative with type 1 diabetes, 219 (2.13%) had early-stage disease, or about 1 in 45. Among the 127,754 participants without that family history, 408 (0.32%) had early-stage disease, or about 1 in 350.

Rates among children without a family history varied by country, from 0.22% in Germany to 0.47% in Sweden. They also rose with age, from 0.22% in children younger than 4 to 0.40% in children ages 8 to 12.

Out of the 634 participants identified with early-stage disease, 386 completed follow-up testing to determine their stage. Most (78%) were in stage 1 and 18% were in stage 2. Sixteen children (4.1%) had already progressed to stage 3 disease.

The authors said the results show that screening methods first developed in Germany “can be successfully applied to regions with different healthcare systems.”

What the new screening guidance recommends

The consensus guidance was developed by an international group of nearly 30 experts convened by Breakthrough T1D, with Ziegler as first author. It has been endorsed by 20 professional and patient organizations, including EASD, the International Society for Pediatric and Adolescent Diabetes and the International Diabetes Federation Europe.

The authors said screening only families with a history of the disease would miss most cases, because more than 85% of people newly diagnosed with type 1 diabetes have no family history. They also noted that the disease progresses at a similar pace in people with confirmed antibodies whether or not they have a family history.

Under the guidance, diagnosis happens in steps. A sensitive screening test comes first, followed by more specific tests and a second blood sample to confirm. Countries can align the testing windows with existing screening programs. They can also start with children at higher risk and expand from there. The authors added that families should get a confirmed diagnosis in person, with psychosocial support available if needed.

A separate 2024 consensus guidance, also led by Breakthrough T1D, covers how to monitor people after they screen positive.

Type 1 diabetes screening and treatment in the U.S.

Screening has gained momentum as treatment options for early-stage disease have grown. The FDA this year expanded the approval of Sanofi’s Tzield (teplizumab) to include children as young as 1 with stage 2 type 1 diabetes, to delay the onset of stage 3 disease. The FDA also granted accelerated approval for teplizumab in children and teens with newly diagnosed stage 3 disease, with a required follow-up study to confirm clinical benefit.

Breakthrough T1D is funding a series of pilot screening programs across the U.S. The EDENT1FI authors said the next step is to make screening for early-stage type 1 diabetes in the general population part of standard medical care.

Italy has already passed legislation for nationwide type 1 diabetes screening, although the national government and regional health systems are still working to put the law into practice, according to EASD.