Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes

OBJECTIVE <p>Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed < 7 years compared with those diagnosed ≥ 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. </p> <p>RESEARCH DESIGN AND METHODS</p> <p>We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profile and HLA class II associated disease risk between three groups formed based on age at diagnosis; <7, 7–12 and ≥13 years. </p> <p>RESULTS</p> <p>We found significant age-related differences in most of the characteristics analyzed. Children diagnosed < 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 to older children. Those diagnosed ≥ 13 years had a considerably higher male preponderance, a higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis and more severe metabolic decompensation, reflected e.g. by a higher frequency of diabetic ketoacidosis.</p> <p>CONCLUSIONS</p> <p>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.</p>