Screening children for type 1 diabetes-associated islet autoantibodies at ages 2 years and 6 years would identify most of those who go on to develop the condition by mid-adolescence, new data suggest.

Both genetic screening and islet-cell autoantibody screening for type 1 diabetes risk have become less expensive in recent years. Nonetheless, as of now, most children who receive such screening do so through programs that screen relatives of people who already have the condition, such as the global TrialNet program.

Some in the type 1 diabetes field have urged wider screening, with the rationale that knowledge of increased risk can prepare families to recognize the early signs of hyperglycemia and seek medical help to prevent onset of diabetic ketoacidosis.

Moreover, potential therapies to prevent or delay type 1 diabetes are currently in development, including the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio).

However, given that the incidence of type 1 diabetes is about 1 in 300 children, any population-wide screening program would need to be implemented in the most efficient and cost-effective way possible with limited numbers of tests, say Mohamed Ghalwash, PhD, of the Center for Computational Health, IBM Research, Yorktown Heights, New York, and colleagues.

Results from their analysis of nearly 25,000 children from five prospective cohorts in Europe and the United States were published online July 5 in Lancet Diabetes & Endocrinology.

Screening in Kids Feasible, but May Need Geographic Tweaking

“Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics,” Ghalwash and colleagues write.

In an accompanying editorial, pediatric endocrinologist Maria J. Redondo, MD, PhD, writes: “This study is timely because recent successes in preventing type 1 diabetes highlight the need to identify the best candidates for intervention…This paper constitutes an important contribution to the literature.”

However, Redondo, of Baylor College of Medicine and Texas Children’s Hospital, Houston, also cautioned: “It remains to be seen whether Ghalwash and colleagues’ strategy could work in the general population because all the participants in the combined dataset had genetic risk factors for the disease or a relative with type 1 diabetes, in whom performance is expected to be higher.”

She also noted that most participants were of northern European ancestry and that it is unknown whether the same or a similar screening strategy could be applied to individuals older than 15 years, in whom preclinical type 1 diabetes progresses more slowly.

Two-Time Childhood Screening Yielded High Sensitivity, Specificity

The data from a total of 24,662 participants were pooled from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the United States (DAISY and DEW-IT).

All were at elevated risk for type 1 diabetes based on human leukocyte antigen (HLA) genotyping, and some had first-degree relatives with the condition. Participants were screened annually for three type 1 diabetes-associated autoantibodies up to age 15 years or the onset of type 1 diabetes.

During follow-up, 672 children developed type 1 diabetes by age 15 years and 6050 did not. (The rest hadn’t yet reached age 15 years or type 1 diabetes onset.) The median age at first appearance of islet autoantibodies was 4.5 years.

A two-age screening strategy at 2 years and 6 years was more sensitive than screening at just one age, with a sensitivity of 82% and a positive predictive value of 79% for the development of type 1 diabetes by age 15 years.

The predictive value increased with the number of autoantibodies tested. For example, a single islet autoantibody at age 2 years indicated a 4-year risk of developing type 1 diabetes by age 5.99 years of 31%, while multiple antibody positivity at age 2 years carried a 4-year risk of 55%.

By age 6 years, the risk over the next 9 years was 39% if the test had been negative at age 2 years and 70% if the test had been positive at 2 years. But overall, a 6-year-old with multiple autoantibodies had an overall 83% risk of type 1 diabetes regardless of the test result at 2 years.

The predictive performance of sensitivity by age differed by country, suggesting that the optimal ages for autoantibody testing might differ by geographic region, Ghalwash and colleagues say.

Redondo commented, “The model might require adaptation to local factors that affect the progression and prevalence of type 1 diabetes.” And, she added, “important aspects, such as screening cost, global access, acceptability, and follow-up support will need to be addressed for this strategy to be a viable public health option.”

The study was funded by JDRF. Ghalwash and another author are employees of IBM. A third author was a JDRF employee when the research was done and is now an employee of Janssen Research and Development. Redondo has reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online July 5, 2022. Article, Editorial

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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