2376-P: Impact of Autoimmune Hypothyroidism and Celiac Disease on Progression to Diabetes in GAD- or IA-2–Positive Individuals

Introduction and Objective: Recent evidence suggests that the risk of developing autoimmune diabetes is higher in individuals with autoimmune hypothyroidism (AH) or celiac disease (CD). We aimed to assess whether a diagnosis of AH or CD influences the risk of progression to clinical diabetes among normoglycemic or dysglycemic individuals who tested positive for autoantibodies against glutamic acid decarboxylase (GAD) or islet antigen-2 (IA-2). Methods: This retrospective cohort study utilized electronic health records from Maccabi Healthcare Services, Israel. We included individuals of all ages identified between January 1, 2010, and December 31, 2024, who had at least one positive autoantibody (GAD or IA-2). The index date was the first positive autoantibody test. Individuals diagnosed with diabetes within 3 months of the index date were excluded. AH was defined by ICD-9 codes plus positive thyroid peroxidase antibodies; CD was defined by ICD-9 codes. Follow-up concluded at diabetes diagnosis or September 30, 2025. Cox regression models, adjusted for age, sex, and socioeconomic status, estimated hazard ratios (HR) for incident diabetes. Results: We analyzed 363 individuals (mean age 27.1 ± 18.4 years; 52.9% female), of whom 151 (41.6%) were dysglycemic at baseline. During a median follow-up of 5.8 years [IQR 2.2-9.4], 75 individuals (20.7%) developed diabetes, with a median time to diagnosis of 1.6 years [IQR 0.8-3.6]. Progression rates were 35.8% among dysglycemic versus 9.9% among normoglycemic individuals (P < 0.001). At the end of follow-up, the prevalence of AH or CD was significantly higher in progressors versus non-progressors (21.3% vs. 10.4%; P = 0.01). The HR for incident diabetes was 2.23 (95% CI 1.27-3.91) for individuals with AH or CD compared to those without either. When analyzed separately, the HR was 3.10 (95% CI 1.32-7.28) for AH and 1.94 (95% CI 1.01-3.74) for CD. Conclusion: In individuals with islet autoimmunity, concurrent AH or CD was independently associated with a higher risk of incident diabetes. Disclosure A. Nakhleh: None. N. Shehadeh: None.