Islet autoantibody types mark differential clinical characteristics at diagnosis of pediatric type 1 diabetes

Abstract

Background: We aimed to study whether islet autoantibody type marks differential characteristics at the time of type 1 diabetes (T1D) diagnosis.

Methods: We studied 711 children with newly diagnosed autoimmune T1D. We compared demographic (sex, age, race/ethnicity), clinical (pubertal development, BMI percentile, diabetic ketoacidosis [DKA]) and laboratory (glucose, hemoglobin A1c [HbA1c], C-peptide, tissue transglutaminase antibodies [tTGA], thyroglobulin antibodies, and thyroid peroxidase antibodies [TPOA]) characteristics by presence/absence of autoantibodies to insulin (IAA), GAD65 (GADA), or IA-2/ICA512 (IA-2A). Islet autoantibody titers were evaluated among the children positive for the relevant autoantibody type. We used multivariable analysis to adjust for potential confounders.

Results: IAA+ was statistically associated with younger age (p < 0.0001) and lower HbA1c (p = 0.049) while Tanner stage, GADA status and number of positive islet autoantibodies were not significant in the multivariable model. GADA+ was associated with female sex (OR = 4.0, p = 0.002) and negatively with elevated tTGA titers (>50 U/mL) (OR = 0.21, p = 0.026) but not with age, IAA status, IA-2A status, islet autoantibody number, or thyroid autoimmunity. None of the associations with IA-2A positivity was statistically significant in the multivariable analysis. In multivariable models, IAA titer was significantly associated with younger age (p = 0.006), DKA (p = 0.017) and higher tTGA levels (p = 0.002); GADA titer with female sex (p = 0.028), racial minority (p = 0.046) and TPOA positivity (p = 0.021); and IA-2A titer with older age (p = 0.001) and not being African American (p = 0.024).

Conclusions: Islet autoantibody type is associated with differential characteristics at diagnosis of pediatric T1D. Longitudinal and mechanistic studies are needed to evaluate T1D endotypes by autoantibody type.

Keywords: autoantibody; diagnosis; heterogeneity; pediatric; type 1 diabetes.