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Children with type 1 diabetes of early age at onset - immune and metabolic phenotypes
Madalena Sales Luis1,2, Margarida Alcafache1, Sara Ferreira1
1Paediatric Endocrinology and Diabetology Unit, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
Insights
Children with early-onset type 1 diabetes (T1D) show increased autoimmune diseases and antibodies, with lower initial insulin production and higher insulin needs post-diagnosis. This suggests a distinct, faster-progressing disease phenotype in younger children with T1D.
Area of Science:
- Pediatrics
- Immunology
- Endocrinology
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction.
- Early age at onset (EAO) in T1D may represent distinct clinical and immunological phenotypes.
- Understanding these phenotypes is crucial for tailored management and therapeutic strategies.
Purpose of the Study:
- To evaluate clinical, immune, and metabolic features of T1D in children with early age at onset (EAO; ≤5 years) compared to later age at onset (LAO; >5 years).
- To identify age-related disease phenotypes in pediatric T1D.
- To investigate associations between EAO and other autoimmune diseases, ketoacidosis, immunological profiles, and metabolic outcomes.
Main Methods:
- A comparative study involving 137 children with T1D, divided into EAO (n=52) and LAO (n=85) groups.
- Assessment of concomitant autoimmune diseases, diabetes ketoacidosis at onset, and immunological markers.
- Collection of metabolic data, including C-peptide levels and hemoglobin A1c (HbA1c), one year post-diagnosis.
- Statistical analysis using p<0.05 as the significance threshold.
Main Results:
- EAO was significantly associated with a higher prevalence of concomitant autoimmune diseases (p=0.032).
- Children with EAO exhibited lower C-peptide levels (p=0.01) and a higher absolute lymphocyte count (p<0.0001) at onset, with an inverse correlation between these parameters (p=0.028).
- The EAO group showed a higher frequency of multiple autoantibodies (p=0.0008), particularly insulin antibodies (p=0.0001), and required higher total daily insulin (TDI) doses one year post-diagnosis (p=0.008) despite similar HbA1c levels.
Conclusions:
- Early age at onset T1D is linked to increased autoimmune comorbidities, a greater antibody burden, and diminished initial insulin secretion.
- Patients with EAO demonstrate a more pronounced immune dysregulation and potentially faster disease progression.
- These findings suggest distinct immunogenetic profiles and immune environments based on age at T1D onset, necessitating further research for improved patient stratification and novel therapeutic targets.
Abstract:
Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct "immune environment" with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.
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