Glutamic Acid Decarboxylase Autoantibodies (GADA) in Type 2 Diabetes Predict Glycemic Control over 16 Years

A minority of adults diagnosed with type 2 diabetes (T2D) have islet autoantibodies that may predict diabetes progression. We investigated the association between GADA, the most prevalent islet autoantibody, and longitudinal HbA1c in Look AHEAD (Action for Health in Diabetes), a trial that randomized adults with clinically-diagnosed T2D and overweight/obesity 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 analyzed the association between GADA category and HbA1c (yearly through year 4, then on alternating years) using linear mixed effects regression adjusted for age, sex, race/ethnicity, calendar time and study arm. 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 15.9 years, the modeled mean HbA1c was 7.24% in GADA-, 7.49% in low-level GADA, and 7.67% in high-level GADA (p<0.001). GADA+ participants had consistently higher HbA1c over follow-up in both study arms (Figure). In conclusion, a substantial minority of adults with clinically-diagnosed T2D had GADA positivity that predicted worse glycemic control for more than a decade. 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)