1308-P: Glutamic Acid Decarboxylase Autoantibodies (GADA) in Type 2 Diabetes Do Not Predict Long-Term Diabetes Complications

Abstract

Some adults with type 2 diabetes (T2D) have islet autoantibodies that may explain clinical heterogeneity, yet limited long-term studies have examined their relationship with diabetes outcomes. We investigated the association between GADA, the most prevalent islet autoantibody, and diabetes complications and mortality in Look AHEAD (Action for Health in Diabetes), a trial that randomized adults with clinically-diagnosed T2D to intensive lifestyle intervention vs. control for 9.6 years, and then followed them observationally. GADA was measured by radioligand binding assay in 87% of the cohort at baseline and categorized as negative, low-level (35-199 U/mL) or high-level (≥200 U/mL). We used Cox proportional hazards regression adjusted for age, sex, race/ethnicity, and study arm to analyze the association between GADA category and time-to-event outcomes: CVD (MI, stroke, hospitalized angina, CVD death), incident eGFR <45 ml/min/1.73m2, incident end stage kidney disease, and all-cause mortality. Among 4,492 participants, the median age was 59 years and diabetes duration 5 years. GADA was low-level and high-level positive in 131 (2.9%) and 85 (1.9%), respectively. Over a median follow-up of 17 years, there was no significant association between GADA levels and outcomes (Table). Overall, the presence of GADA above 35 U/mL was not predictive of CVD, or renal outcomes or mortality. Disclosure S.J.Pilla: None. A.Ramelius: None. R.Bennet: None. Å.Lernmark: Advisory Panel; Diamyd Medical. N.N.Mathioudakis: None. J.Clark: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions. W.C.Knowler: None. A.Balasubramanyam: None. C.S.Hampe: Employee; Immusoft corp. S.Pietropaolo: None. A.M.Anderson: None. M.Li: None. N.Zhao: None. S.L.Zeger: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126825, K23DK128572)