Islet Autoantibody Tests at 2 Ages Predict Pediatric T1D

Initial screening for islet autoantibodies at ages 2 and 6 years demonstrated high sensitivity and efficiency at predicting type 1 diabetes (T1D) onset, according to a study published in The Lancet Diabetes & Endocrinology.

The study authors also noted that screenings at these 2 ages could be implemented in clinical practice, but may need to be adjusted based on country due to varying disease characteristics specific to each population.

“Early prediction of childhood type 1 diabetes reduces ketoacidosis at diagnosis and provides opportunities for disease prevention,” the authors explained. “However, only highly efficient approaches are likely to succeed in public health settings.”

To identify the best approach for an initial islet autoantibody screening in children younger than 15 years, the authors gathered data from 5 prospective cohorts in Finland, Germany, Sweden, and the United States and entered the data into the T1D Intelligence (T1DI) cohort.

Data were available for a total of 24,662 children at high risk for T1D who were enrolled in their respective cohorts prior to age 2. Of this group, only 6722 were followed up for islet autoantibodies and T1D until age 15 or T1D onset, whichever occurred earlier.

The authors found that 672 children developed T1D by age 15, while 6050 did not. They also noted that about 74% of children in the cohort did not have an immediate family member with T1D.

A median (IQR) of 18 (14-24) samples were collected per participant and analyzed for islet autoantibodies. Median (IQR) age at first test was 4.2 (2.4-9.6) months, follow-up was 15.4 (15.0-17.5) years, and age at first appearance of islet autoantibodies was 4.5 (2.0-8.6) years.

The optimal screening ages for 2 measurements were ages 2 and 6, which demonstrated a sensitivity of 82% (95% CI, 79-86) and a positive predictive value (PPV) of 79% (95% CI, 75-80) for T1D onset by age 15.

“For the prediction of diabetes, we found that screening at two ages was better than screening at a single age and that the presence of any islet autoantibodies had greater comparative sensitivity but lower PPV than the presence of multiple islet autoantibodies,” the authors wrote.

Additionally, islet autoantibody positivity at the beginning of both optimal test ages was highly predictive of T1D diagnosis in the subsequent age intervals of 2 and 5.99 years and 6 and 15 years. Among children who received a T1D diagnosis later in childhood, the autoantibodies usually appeared before age 6.

Another important observation the authors noted was that sensitivity was similar between high and moderate human leukocyte antigen risk, suggesting the screening method works for patients with varying risk.

“When used after genetic prescreening, the majority of future cases should be detected, all at a net investment of less than one islet-autoantibody measurement per child,” the authors said. “Following children with any islet autoantibodies rather than just multiple islet autoantibodies increases case detection with acceptable predictive value.”

Reference

Ghalwash M, Dunne JL, Lundgren M, et al. Two-age islet-autoantibody screening for childhood type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. Published online July 5, 2022. doi:10.1016/S2213-8587(22)00141-3