1298-P: Independent Associations of GAD65, IA2, and ZnT8 Autoantibody (Ab) Positivity with C-Peptide (CPep) in a Diverse Cohort of Youth with Diabetes (DM)

Abstract

The current DM classification does not fully enable precision medicine in DM due to heterogeneity between and within DM types, especially in racially diverse populations. Insulin deficiency (ID) is one of the most clinically actionable DM outcomes and, while its association with islet autoimmunity is known, the influence of Ab type and number after DM onset is uncertain. Thus, we assessed the effect of Ab characteristics on ID (measured as Cpep loss) in youth with established DM. We studied 151 youth with DM (median [IQR] age 15.0 [4.2] yrs, DM duration 5.4 [3.4] yrs), 61% female, 53% Hispanic and 17% non-Hispanic African American. We measured postprandial serum Cpep, glucose and Ab (GAD65, IA2 and ZnT8) and collected clinical/demographic data. Cpep loss was pre-specified as postprandial CPep <0.6 ng/ml. We found 0, 1, 2, or 3 +Ab in 34%, 22%, 31% and 13% of participants, respectively (Figure, left panel). A Breslow-Day statistic suggested homogeneity of the risk ratios across the 3 Ab types for CPep loss (p = 0.42), which were all larger than 1 (Figure, right panel). Cpep loss was significantly associated with ≥1 (vs 0) Ab+ (p < 0.0001) but not with single (vs multiple) Ab+ (p = 0.60). In sum, each of GAD65, IA2 and ZnT8 Ab are significantly associated with ID among diverse youth with DM. This suggests that models predicting ID post-onset should include each of GAD65, IA2 and ZnT8 Ab. Disclosure M.J.Redondo: None. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. D.Dabelea: None. W.Hagopian: Research Support; Janssen Research & Development, LLC, Provention Bio, Inc., Randox R & D. Discover study group: n/a. K.K.Harrall: None. D.H.Glueck: None. M.Tosur: Advisory Panel; Provention Bio, Inc. S.Uysal: None. A.Muir: None. K.Vehik: None. T.M.Brusko: Consultant; Repertoire Immune Medicines, Quell Therapeutics, Research Support; Immunocore, Ltd., Adaptive Biotechnologies. M.A.Atkinson: None. Funding National Institutes of Health (R01DK124395)