One-Time Islet Autoantibody Testing Can Predict T1D Development in Adolescents

A single screening of 10-year-old adolescents at risk for type 1 diabetes (T1D) to detect islet autoantibodies was highly effective at predicting whether they would develop T1D by age 18. This, in turn, could prevent the occurrence of diabetic ketoacidosis and allow for participation in secondary prevention trials.

These findings were published in The Lancet Child & Adolescent Health.

Data from studies conducted in Finland (Diabetes Prediction and Prevention study), Germany (BABYDIAB study), and the United States (Diabetes Autoimmunity Study in the Young, Diabetes Evaluation in Washington study) were harmonized, bringing together data of 20,303 children with increased risk of T1D.

Of this group, 8682 children were included for analysis using inverse probability censoring weighting, and 1890 children received follow-up until they reached 18 years of age or developed T1D between ages 10 and 18 years. The median (IQR) follow-up was 18.3 (14.5-20.3) years of age and a median of 16 (10–21) samples per participant were analyzed for islet autoantibodies. Children who were lost to follow-up or received a T1D diagnosis before the age of 10 were excluded from the analysis.

At each follow-up visit after the initial screening, autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured. The study's primary outcomes were the sensitivity and positive predictive value of these autoantibodies when tested at 1 or 2 ages to predict T1D by age 18.

Of 1890 adolescents, 442 (23.4%) screened positive for at least 1 islet autoantibody, and 262 (13.9%) developed T1D by age 18. The authors also found that, for each 1-year increment of age at T1D diagnosis, time between seroconversion and T1D diagnosis increased by 0.64 years (95% CI, 0.34-0.95). The median (IQR) interval between the last prediagnostic sample and T1D diagnosis was 0.3 years (0.1-1.3) in the 227 adolescents who were autoantibody positive and 6.8 years (1.6-9.9) years in the 35 adolescents who were autoantibody negative.

When evaluating only children who completed both testing and observation, the observed sensitivity for one-time screening at age 10 was very high at 90% (95% CI, 86%-95%), with a positive predictive value of 66% (60%-72%). When screening at the ages 10 and 14 years, the observed sensitivity increased slightly to 93% (95% CI, 89%-97%) while the positive predictive value decreased to 55% (95% CI, 49%-60%).

“Childhood type 1 diabetes is most prevalent in northern European populations, and the current results can first be applied in these countries,” the authors said. “Although the incidence of type 1 diabetes is lower elsewhere, the much larger childhood populations in these settings mean that screening for islet autoimmunity could save larger numbers of children from diabetic ketoacidosis.”

The authors further compared the differences between screening once and twice.

Screening just once at 10 years showed the highest comparative sensitivity of 63% (95% CI, 56%-71%), with a corresponding positive predictive value of 38% (95% CI, 32%-46%) and specificity of 38% (95% CI, 36%-40%).

When screening was performed twice at ages 10 and 14, the comparative sensitivity improved to 72% (95% CI, 65%-78%) and specificity increased to 63% (95% CI, 61%-66%), but the positive predictive value decreased to 29% (95% CI, 24%-34%).

According to the authors, this analysis demonstrates that single islet autoantibody screening at age 10 is an effective method of identifying adolescents at high risk of developing T1D, and screening twice at the ages of 10 and 14 improves sensitivity only marginally.

“Given that the cost of two­-age screening is twice that of a single screening, we consider a single screening at 10 years of age a good choice,” the authors said. “However, the acceptability of islet autoantibody screening by families, adolescents, and clinicians is important to consider when planning screening programmes for islet autoimmunity. Single testing might be more economical and more acceptable, but this needs to be evaluated in the setting of each specific country.”

Reference

Ghalwash M, Anand V, Lou O, et al; Type 1 Diabetes Intelligence Study Group. Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study. Lancet Child Adolesc Health. 2023;7(4):261-268. doi:10.1016/S2352-4642(22)00350-9