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, 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.

Keywords: Age; Beta cell function; C-peptide; Prevention; Subgroups; Treatment; Type 1 diabetes.

Fig. 1

Time course of glucose metabolism variables during the first 12 months post diagnosis by age group. Data are shown as median and IQR for fasting C-peptide (a), fasting glucose (b), AUC C-peptide (c), AUC glucose (d), HbA_1c (e), insulin dose (f) and IDAA1c (g). Number of participants with completed data at baseline by age group (1–9; 10–17; 18–45 years): fasting C-peptide (246; 244; 92), fasting glucose (246; 244; 92), AUC C-peptide (134; 188; 69), AUC glucose (140; 205; 75), HbA_1c (249; 253; 92), insulin dose (264; 256; 93) and IDAA1c (242; 241; 86)

Fig. 2

Participants with HbA_1c <53 mmol/mol and IDAA1c ≤9 at baseline and follow-up. (a, b) Proportion of all study participants with HbA_1c <53 mmol/mol (orange bars) or HbA_1c ≥53 mmol/mol (green bars) at baseline and follow-up visits (3, 6, 12 months) (a), and divided by age groups (1–9, 10–17 and 18–45 years) (b). (c, d) Proportion of all participants with IDAA1c ≤9 (green bars) or IDAA1c >9 (orange bars) at baseline and follow-up visits (3, 6, 12 months) (c) and divided by age groups (1–9, 10–17 and 18–45 years) (d)