ESPE Yearbook of Paediatric Endocrinology

Brief summary: Using data from the Type 1 Diabetes Intelligence (T1DI) cohort (n=24 662), this prospective study aimed to identify optimal ages for initial islet autoantibody (IAb) screening to predict the development of clinical type 1 diabetes (T1D). The identified optimal screening ages were 2 years and 6 years, with sensitivity of 82% and positive predictive value of 79% for T1D by age 15 years.

Screening for T1D is a growing research topic and, although for many years the focus has been on family members of individuals with T1D, it is now extending to general population screening (1). As for any potential new screening program, several aspects should be considered and the classical Wilson & Jungner criteria should be fulfilled (2). One important question is the optimal age for IAb testing.

In this large study combining data from 5 prospective birth cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the USA (DAISY and DEW-IT), 6722 out of the total 24 662 children were followed up to age 15 years or until onset of T1D, with 672 developing T1D. The main finding was that screening at only two ages (2 years and 6 years) can identify most children (4 out of 5) who will develop T1D by age 15 years. This is important because fewer tests means lower screening costs and greater accessibility. Indeed, for wide implementation of population screening several aspects need to be considered: costs, global access, acceptability, and monitoring and support/education programs for people identified at-risk.

Previous epidemiological data showed that seroconversion occurs during infancy and early childhood with a peak around the age of 1–1.5 years (3). The proposed two-age approach aims to catch as many cases as possible. However, one limitation of first screening at age 2 is that it would miss the small number of very young children who develop T1D before age 2 and who often have the highest rates of DKA at diagnosis.

The study also confirmed that, after the detection of islet autoantibodies, the rate of progression to clinical T1D varies depending on genetics, autoantibody characteristics (number, type, and titre), metabolic parameters and demographic factors (age, race and ethnicity, and sex). Some differences in prediction performance were found among cohorts, likely due to geographical diversity in the genetic and environmental factors, and these factors need to be further investigated in future studies.

References: 1. Sims EK, Besser REJ, Dayan C, et al. Screening for type 1 diabetes in the general population: A status report and perspective. Diabetes. 2022;71(4):610–623. 2. Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. Geneva, World Health Organization, 1968. 3. Krischer JP, Lynch KF, Schatz DA, Ilonen J, Lernmark A, Hagopian WA, et al. The 6-year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015;58(5):980–998.