The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults

Journal article

Aims/hypothesis: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual’s clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. Methods: Data were collected from the large INNODIA cohort of individuals (aged 1.0–45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10–17 years; and ≥18 years. Results: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0–382.0) pmol/l (AUC 749.3 [466.2–1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). Conclusions/interpretation: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline. Graphical Abstract:

Authors: Marcovecchio, ML; Hendriks, AEJ; Delfin, C; Battelino, T; Danne, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Diabetologia
• Volume: 67
• Issue: 6
• Pages: 995-1008
• Publication date: 2024-03-22
• Acceptance date: 2024-01-24
• DOI: 10.1007/s00125-024-06124-5
• EISSN: 1432-0428
• ISSN: 0012-186X
• Language: English
• Keywords: Subgroups; Prevention; Beta cell function; C-peptide; Treatment; Type 1 diabetes; Age