Impact of Autoimmune Hypothyroidism and Celiac Disease on Progression to Diabetes in Individuals Positive for <scp>GAD65</scp> or <scp>IA</scp> ‐2 Autoantibodies

AIMS: To assess whether autoimmune hypothyroidism (AH) or celiac disease (CD) influences diabetes progression among individuals who tested positive on a pooled screening assay for glutamic acid decarboxylase 65 and insulinoma-associated protein 2 autoantibodies (GADA/IA-2A). MATERIAL AND METHODS: This retrospective cohort study used data from Maccabi Healthcare Services, Israel (2010-2024), and included 363 GADA/IA-2A-positive individuals without diabetes. In a 316-patient subcohort, individual GADA autoreactivity was assessed. The primary outcome was incident clinical diabetes. Cox regression estimated hazard ratios (HRs) for incident diabetes associated with AH, CD, and asthma (comparator), modelled as time-dependent covariates, adjusting for age, sex, socioeconomic status and baseline fasting plasma glucose. RESULTS: Over a median 5.8-year follow-up, 75 individuals (20.7%) developed clinical diabetes. Progression occurred in 35.8% of dysglyceamic versus 9.9% of normoglycemic individuals (p < 0.001). The prevalence of AH or CD was higher among progressors (21.3% vs. 10.4%; p = 0.01). Adjusted HRs (95% CI) were 2.55 (1.40-4.64) for the composite of AH or CD, 2.85 (1.00-8.15) for AH, and 2.41 (1.21-4.81) for CD. The HR for the composite association was 3.08 (1.36-3.96) in individuals aged < 18 years and 2.10 (0.86-5.12) in adults (p for interaction = 0.56). In a secondary analysis of the subcohort with individual GADA assessment (n = 316), further adjustment for GADA status attenuated the composite HR to 1.97 (1.06-3.65). CONCLUSIONS: Concurrent AH or CD is associated with accelerated diabetes progression in autoantibody-positive individuals. Although this partly reflects a shared polyautoimmune predisposition, both conditions may serve as accessible markers for risk stratification.