Children with type 1 diabetes of early age at onset - immune and metabolic phenotypes.
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.
['Sales Luis|Madalena|M|https://orcid.org/0000-0002-0324-0486', 'Alcafache|Margarida|M|', 'Ferreira|Sara|S|', 'Fitas|Ana Laura|AL|', 'Simões Pereira|Joana|J|https://orcid.org/0000-0002-7119-5058', 'Caramalho|Íris|Í|', 'Lopes|Lurdes|L|', 'Limbert|Catarina|C|']
D000293:Adolescent D017668:Age of Onset D001323:Autoantibodies D001327:Autoimmune Diseases D015415:Biomarkers D001786:Blood Glucose D002096:C-Peptide D002648:Child D002675:Child, Preschool D003922:Diabetes Mellitus, Type 1 D016883:Diabetic Ketoacidosis D005260:Female D005500:Follow-Up Studies D006442:Glycated Hemoglobin A D006801:Humans D007004:Hypoglycemic Agents D007223:Infant D007231:Infant, Newborn D007328:Insulin D008297:Male D010641:Phenotype D011379:Prognosis D012189:Retrospective Studies
type 1 diabetes autoantibodies early onset innate immunity β-cells