TY - JOUR
T1 - The INNODIA Type 1 Diabetes Natural History Study
T2 - a European cohort of newly diagnosed children, adolescents and adults
AU - Marcovecchio, M Loredana
AU - Hendriks, A Emile J
AU - Delfin, Carl
AU - Battelino, Tadej
AU - Danne, Thomas
AU - Evans, Mark L
AU - Johannesen, Jesper
AU - Kaur, Simranjeet
AU - Knip, Mikael
AU - Overbergh, Lut
AU - Pociot, Flemming
AU - Todd, John A
AU - Van der Schueren, Bart
AU - Wicker, Linda S
AU - Peakman, Mark
AU - Mathieu, Chantal
AU - INNODIA consortium
N1 - © 2024. The Author(s).
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Autoantibodies/blood
KW - Blood Glucose/metabolism
KW - C-Peptide/blood
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Diabetes Mellitus, Type 1/diagnosis
KW - Europe/epidemiology
KW - Female
KW - Glycated Hemoglobin/metabolism
KW - Humans
KW - Infant
KW - Insulin-Secreting Cells/metabolism
KW - Male
KW - Middle Aged
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85188308637&partnerID=8YFLogxK
U2 - 10.1007/s00125-024-06124-5
DO - 10.1007/s00125-024-06124-5
M3 - Journal article
C2 - 38517484
SN - 0012-186X
VL - 67
SP - 995
EP - 1008
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -