The current binary classification (T1D vs. T2D) is inadequate to comprehensively dissect the heterogeneity of pediatric diabetes. The Aβ classification system, based on presence of islet autoimmunity (A+ or A-) and beta-cell functional reserve (β+ or β-), has been validated to define distinct phenotypic forms of Ketosis-Prone Diabetes in adults. Here, we aimed to study the utility of the Aβ classification system in children with new-onset diabetes. “A+” was defined as presence of ≥1 islet autoantibodies (GAD65, ICA512, insulin and ZnT8 autoantibodies) and “β+” as random C-peptide level ≥0.6 ng/mL at diagnosis. We compared the clinical characteristics at diabetes onset between the groups. The study cohort (n=67) was 46% female, 33% non-Hispanic white, 43% Hispanic, 21% non-Hispanic black and 3% Other. Mean age was 11.2 years and mean BMI was 59.3%ile. Aβ classification at diagnosis defined the following groups: A+β- (43%), A+β+ (24%) and A-β+ (33%). There were no A-β- patients. Median C-peptide levels in the three groups were 0.3, 0.7 and 3.3 ng/mL, respectively. Mean BMI %iles were 34.4 in A+β-, 53.1 in A+β+, and 96.4 in A-β+ group (p<0.001). A-β+ group were older (14 y/o) compared to A+β- (8.9 y/o) and A+β+ (11.7 y/o) (p<0.001). Diabetic ketoacidosis at diabetes onset was most frequent in A+β- (69%), intermediate in A+β+ (44%) and least in A-β+ (18%) (p<0.01). Hispanic ethnicity was more common in A-β+ (64%) compared to A+β+ (44%) and A+β- (28%) (p=0.03). There were no significant differences in sex, mean HbA1c and daily insulin dose per kg at diabetes diagnosis between the groups. The Aβ classification system provides more pathophysiologic insight and discrimination of characteristics than the current classification system. The A-β- group, which we previously reported to be 2.6% of a large pediatric diabetes cohort, was not represented in this smaller study. If prospective follow-up confirms distinct natural histories for these groups, the Aβ classification will be useful in clinical practice and for the design of intervention trials.
M. Tosur: Advisory Panel; Self; Provention Bio, Inc. S. Deen: None. S. Uysal: None. M. Astudillo: None. F. Jahoor: None. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc. A. Balasubramanyam: None.
Texas Children’s Hospital