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10-27-2022 | Screening | News

IAA screening may improve classification of autoimmune diabetes in children

Author: Laura Cowen

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medwireNews: Testing for autoantibodies to endogenous insulin (IAA) in addition to regular autoantibody screening can increase the proportion of children with an autoimmune classification for newly diagnosed type 1 diabetes, UK research suggests.

“Robust testing for IAA in children will help inform clinical decision making in young children and make screening for monogenic diabetes more efficient,” write Claire Williams and colleagues from the University of Bristol in Diabetic Medicine.

Williams et al explain that although current UK National Institute for Health and Care Excellence guidelines do not recommend routine testing of islet autoantibodies in children, it is important to identify potential cases of monogenic diabetes (approximately 2.5% of cases in UK children) for subsequent genetic screening and optimal non-insulin treatment strategies.

In their analysis of 486 children (54.1% boys; median age 10.4 years) with newly diagnosed type 1 diabetes, 95.7% were positive for at least one of the three most commonly tested autoantibodies – glutamate decarboxylase 65 (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) – with the majority (81.7%) positive for multiple autoantibodies.

Additional testing for IAA using a high-performance radiobinding assay reclassified nine (42.9%) of the 21 autoantibody negative children as autoantibody positive, thus almost halving the number of children that would be referred for genetic screening, where costs are 10-fold greater than islet autoantibody screening, the researchers note.

The remaining 12 (2.5%) children who were negative for all four autoantibodies were also tested for the recently discovered autoantibody Tetraspanin-7 but no additional cases of autoimmunity were identified. Follow-up data for these children were limited, but one child was subsequently diagnosed with Maturity Onset of Diabetes in the Young.

Williams and team also found that islet autoantibody positivity was significantly associated with age at diagnosis, with the relationship varying among the specific antibodies; IAA positivity decreased with age whereas GADA and ZnT8A positivity increased with age.

In the whole cohort, IAA achieved the highest sensitivity as a single test in children aged below 5 years, with 83 (91.2%) of 91 children positive for IAA. Conversely, GADA was the most sensitive single test for children over 10 years of age, identifying 88.5% of those aged 10–15 years and 90.6% of those aged 15–18 years.

In children aged 5–10 years, all four markers had similar sensitivity, at around 73–79%.

Williams and co-authors conclude: “The optimal strategy to prove autoimmunity or identify possible genetic cases of diabetes is to test for all four islet autoantibodies.”

However, they add: “If cost-saving strategies are required, our study shows that those making clinical decisions regarding genetic screening would be best incorporating IAA testing in young children (<5 years) at diagnosis of diabetes and children >10 years should be screened for GADA.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Diabetic Med 2022; doi:10.1111/dme.14979

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