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

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, 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.

• Authors: M Loredana Marcovecchio, A Emile J Hendriks, Carl Delfin, Tadej Battelino, Thomas Danne, Mark L Evans, Jesper Johannesen, Simranjeet Kaur, Mikael Knip, Lut Overbergh, Flemming Pociot, John A Todd, Bart Van der Schueren, Linda S Wicker, Mark Peakman, Chantal Mathieu, INNODIA consortium
• Journal: Diabetologia (Diabetologia) Vol. 67 Issue 6 Pg. 995-1008 (Jun 2024) ISSN: 1432-0428 [Electronic] Germany
• PMID: 38517484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2024. The Author(s).

Chemical References

• C-Peptide
• Autoantibodies
• Glycated Hemoglobin
• Blood Glucose

Topics

• Humans
• Diabetes Mellitus, Type 1 (diagnosis, blood, epidemiology)
• Adolescent
• Child
• Male
• Female
• C-Peptide (blood)
• Adult
• Young Adult
• Child, Preschool
• Autoantibodies (blood)
• Glycated Hemoglobin (metabolism)
• Blood Glucose (metabolism)
• Cohort Studies
• Infant
• Europe (epidemiology)
• Middle Aged
• Insulin-Secreting Cells (metabolism)