A1 Refereed original research article in a scientific journal
Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes
Authors: Parviainen Anna, Härkönen Taina, Ilonen Jorma, But Anna, Knip Mikael; The Finnish Pediatric Diabetes Register
Publisher: NLM (Medline)
Publication year: 2022
Journal: Diabetes Care
Journal name in source: Diabetes care
Volume: 45
Issue: 4
First page : 871
Last page: 879
eISSN: 1935-5548
DOI: https://doi.org/10.2337/dc21-1251(external)
Web address : https://doi.org/10.2337/dc21-1251
OBJECTIVE
Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age <7 years compared with those diagnosed at age ≥13 years. We set out to explore whether variation in demographic, clinical, autoimmune, and genetic characteristics of children and adolescents with newly diagnosed type 1 diabetes support the existence of these proposed endotypes.
RESEARCH DESIGN AND METHODS
We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6,015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profiles, and HLA class II–associated disease risk between three groups formed based on age at diagnosis: <7, 7–12, and ≥13 years.
RESULTS
We found significant age-related differences in most of the characteristics analyzed. Children diagnosed at age <7 years were characterized by a higher prevalence of affected first-degree relatives, stronger HLA-conferred disease susceptibility, and higher number of autoantibodies at diagnosis, in particular a higher frequency of insulin autoantibodies, when compared with older children. Those diagnosed at age ≥13 years had a considerably higher male preponderance, higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation, reflected, for example, by a higher frequency of diabetic ketoacidosis.
CONCLUSIONS
Our findings suggest that the heterogeneity of type 1 diabetes is associated with the underlying disease process and support the existence of distinct endotypes of type 1 diabetes related to age at diagnosis.