The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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, HbA 1c 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. HbA 1c 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
Source: Diabetologia
Institutions: University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Novo Nordisk (Denmark), University of Ljubljana, Ljubljana University Medical Centre, Kinderkrankenhaus auf der Bult, Wellcome/MRC Institute of Metabolic Science, University of Copenhagen, Herlev Hospital, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, University of Helsinki, Helsinki University Hospital, Helsinki Children's Hospital, KU Leuven, Centre for Human Genetics, University of Oxford, Sanofi (United States)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,290
Funders: Leona M. and Harry B. Helmsley Charitable Trust, Wellcome Trust, Nottingham University Hospitals NHS Trust, University Hospitals of Leicester NHS Trust, European Federation of Pharmaceutical Industries and Associations, Steno Diabetes Center Copenhagen, National Institute for Health and Care Research, University of Oxford, University of Nottingham, Universität Wien, Novo Nordisk, Medizinische Universität Wien, Innovative Medicines Initiative, Barts Health NHS Trust, NIHR Cambridge Biomedical Research Centre
OpenAlex ID: W4393085378