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

• Published in: Diabetologia Vol. 67; no. 6; pp. 995 - 1008
• Main Authors: Marcovecchio, M. Loredana, Hendriks, A. Emile J., Delfin, Carl, Battelino, Tadej, Danne, Thomas, Evans, Mark L., Johannesen, Jesper, Kaur, Simranjeet, Knip, Mikael, Overbergh, Lut, Pociot, Flemming, Todd, John A., Van der Schueren, Bart, Wicker, Linda S., Peakman, Mark, Mathieu, Chantal
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2024; Springer Nature B.V
• Subjects: Adolescent; Adult; Age; Age differences; Age groups; Autoantibodies; Autoantibodies - blood; Beta cells; Blood Glucose - metabolism; C-Peptide - blood; Child; Child, Preschool; Cohort Studies; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - epidemiology; Diagnosis; Europe - epidemiology; Fasting; Female; Glycated Hemoglobin - metabolism; Human Physiology; Humans; Infant; Insulin-Secreting Cells - metabolism; Internal Medicine; Ketoacidosis; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Peptides; Population studies; Teenagers; Young Adult; Europe; Prevention; Treatment; Type 1 diabetes; C-peptide; Beta cell function; Age; Subgroups
• DOI: 10.1007/s00125-024-06124-5
• EISSN: 1432-0428
• ISSN: 0012-186X

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