Islet autoantibody types mark differential clinical characteristics at diagnosis of pediatric type 1 diabetes. Issue 6 (31st May 2021) - Nieto, Jacobo
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. Abstract :