1388-P: Clinical Features Associated with Glutamic Acid Decarboxylase Autoantibodies (GADA) in Adults with Type 2 Diabetes

Abstract

Islet autoantibodies in adults classified as having type 2 diabetes (T2D) have been associated with lower adiposity and early insulin requirement. We examined the association between GADA, the most prevalent islet autoantibody, and baseline clinical features in Look AHEAD (Action for Health in Diabetes), a randomized trial of adults with clinically-diagnosed T2D and overweight/obesity from 16 geographically diverse U.S. study centers. GADA was measured by radioligand binding assay in 87% of the randomized cohort at study baseline and categorized as negative (GADA-), low-level (35-199 U/mL, GADA+) or high-level (≥200 U/mL, GADA++). We compared clinical features across GADA categories using Fisher’s exact or Kruskal-Wallis tests. There were 4,492 participants who had a median age 59 years and diabetes duration 5 years. Participants were 59% female, 67% white, 16% Black and 13% Hispanic. GADA was positive (≥35 U/mL) in 216 participants (4.8%); 131 were GADA+ (2.9%) and 85 GADA++ (1.9%). Insulin was used by 15% of GADA-, 25% of GADA+, and 40% of GADA++ (p<0.001). The median HbA1c was 7.0% in GADA-, 7.1% in GADA+, and 7.4% in GADA++ (p=0.004). There was a history of hypothyroidism in 12% of GADA-, 14% of GADA+, and 29% of GADA++ (p<0.001). There was a history of hyperthyroidism in 2% of GADA-, 2% of GADA+, and 7% of GADA++ (p=0.006). GADA level was not associated with age, sex, race/ethnicity, diabetes duration, BMI, waist circumference, or history of microvascular or macrovascular complications. In conclusion, a substantial minority of this population of adults with overweight/obesity who were clinically diagnosed as T2D have GADA positivity, and high levels were strongly associated with phenotypic differences including insulin use and thyroid disease. In contrast to prior studies, GADA was not associated with lower adiposity. These findings highlight the heterogeneity of this population and the need to further study the clinical implications of GADA positivity. 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)