ESPE Yearbook of Paediatric Endocrinology

Diabetes Care. 2022 Apr 1;45(4):871-879. https://pubmed.ncbi.nlm.nih.gov/35147706/

Brief Summary: This Finnish cross-sectional register-based study of 6015 youth with new onset type 1 diabetes (T1D) explored potential differences in clinical, autoimmune and genetic characteristics across three age groups: <7, 7-12 and ≥13 years. Significant differences emerged primarily between the youngest and oldest age groups, confirming a substantial T1D heterogeneity associated with age at diagnosis.

Previous studies have highlighted the heterogeneity of T1D and introduced the important concept of age-related ‘endotypes’, which are disease subtypes defined by distinct pathophysiological mechanisms (1). Substantial differences were previously identified between children diagnosed <7 years vs ≥13 years. The former group was characterized by a hyperimmune pattern of insulitis, less residual insulin-containing islets, abnormal proinsulin processing and lower circulating C-peptide (2,3).

The present study explores differences in clinical and biochemical characteristics across different age groups, using a large population of Finnish youth newly diagnosed with T1D. The study confirms clear differences in children based on their age at diagnosis, particularly between the youngest and oldest age groups, with intermediate characteristics for the age group 7-12 years. Children diagnosed at age <7 years had a higher prevalence of affected first-degree relatives, stronger at-risk HLA, and higher number of autoantibodies than older children. This supports a more aggressive autoimmune process. This age group also showed shorter duration of symptoms and metabolic decompensation, likely reflecting higher awareness and recognition of early symptoms, which could be partly influenced by the higher prevalence of affected family members. Those diagnosed when ≥13 years had higher male preponderance, frequency of GAD autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation.

Overall, these data provide further support to the concept that T1D is not a single disease but that distinct endotypes exist. Further understanding of these endotypes is essential to inform the design of future immunotherapeutic interventions to arrest or prevent T1D.

References: 1. Battaglia M, Ahmed S, Anderson MS, et al. Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes. Diabetes Care 2020;43:5–12. 2. Arif S, Leete P, Nguyen V, et al. Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes 2014;63:3835–45. 3. Leete P, Oram RA, McDonald TJ, et al. Studies of insulin and proinsulin in pancreas and serum support the existence of aetiopathological endotypes of type 1 diabetes associated with age at diagnosis. Diabetologia 2020;63:1258–1267.