ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 10.6 | DOI: 10.1530/ey.18.10.6

JAMA. 2020;323(4):339–351. doi: 10.1001/jama.2019.21565

This study aimed to determine the prevalence of pre-symptomatic T1D in young children participating in a public health screening program for islet autoantibodies and the risk for progression to clinical T1D in children carrying multiple autoantibodies. On screening, 0.03% were found to have clinical T1D. Of the 0.31% who were found to have pre-symptomatic T1D, 24.9% developed clinical T1D during the 3-year follow-up.

Public health screening for T1D in its pre-symptomatic stages may reduce disease severity and burden on a population level. In this study, screening for islet autoantibodies was offered to children aged 1.75 to 5.99 years in Bavaria, Germany, between 2015 and 2019 by primary care pediatricians during routine well-baby visits. Children with multiple islet autoantibodies were invited to participate in a program of diabetes education, metabolic staging, assessment of psychological stress associated with the diagnosis, and prospective follow-up for progression to clinical T1D. The primary outcome was pre-symptomatic T1D, defined as 2 or more islet autoantibodies, with categorization into Stage 1 (normoglycemia), Stage 2 (dysglycemia), or Stage 3 (clinical T1D).

In total, 90,632 children were screened (median [interquartile range {IQR}] age, 3.1 [2.1–4.2] years). Of these, 280 (0.31%) had pre-symptomatic T1D, including 196 (0.22%) with Stage 1, 17 (0.02%) with Stage 2, and 26 (0.03%) with Stage 3 (and 41 were not staged). After a median 2.4 years follow-up, another 36 children developed Stage 3 T1D. The 3-year cumulative risk for Stage 3 T1D among the 280 children with pre-symptomatic T1D was 24.9% ([95% CI, 18.5%–30.7%]; 54 cases; annualized rate, 9.0%). Only two children developed diabetic ketoacidosis. Median (IQR) psychological stress scores were modestly higher at the time of staging in mothers of children with pre-symptomatic T1D (3 [1-7]) compared with mothers of children without islet autoantibodies (2 [1-4]) (P=0.002), but declined after 12 months of follow-up (2 [0-4]) (P<0.001).

This study shows both the potential and benefits of early detection of presymptomatic islet cell autoimmunity as well as the potential risks and drawbacks as shown by severe distress in the families once the diagnosis of asymptomatic albeit proven had been made early.

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