ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This register-based cohort study compared the familial aggregation and heritability of childhood-onset (≤18 years) vs. adult-onset (19-30 years) type 1 diabetes (T1D), using data collected from over 2.9 million individuals born in Sweden between 1982-2010, and from their relatives. Adult-onset T1D showed weaker familial aggregation and lower heritability than childhood-onset T1D.

Although T1D is considered a typical childhood-onset autoimmune condition, it can occur at any age. Indeed, recent data indicate that 62% of all new T1D diagnoses occur in individuals aged 20 years or older (1). Furthermore, T1D shows strong familial aggregation and high heritability (range: 0.50 to 0.88), although previous family-based and twin studies included mostly childhood-onset T1D or a mix of childhood-onset and adult-onset T1D (2).

The current study examined T1D familial aggregation and heritability by age at diagnosis. Having a first-degree relative with T1D conferred a lower risk for adult-onset T1D (hazard ratio (HR)=7.21) than childhood-onset T1D (HR=9.92). The HR of developing T1D at < 30 years was smaller if relatives developed T1D during adulthood than during childhood. Heritability was lower for adult-onset than childhood-onset T1D (0.56 vs 0.81). These findings indicate a larger contribution of environmental factors to the development of T1D in adults than in children and highlight the importance of identifying these factors to potentially prevent T1D.

Study limitations include the upper age limit 30 years, restriction to a single country and small sample size for some types of relatives. However, it sheds light on age-differences in genetic/environmental factors in T1D pathogenesis. Further studies are needed to characterize environmental factors contributing to adult-onset T1D. Understanding these factors is crucial for developing targeted interventions to prevent T1D development and progression.

References: 1. Gregory, G.A., et al., Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diabetes Endocrinol. 2022;10(10):741-760.2. Redondo MJ, Steck AK, Pugliese A. Genetics of type 1 diabetes. Pediatr Diabetes. 2018;19(3):346-53.