Gluten Intake and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in Children at Increased Risk of Disease

Background: Few studies have examined gluten intake as a risk factor for islet autoimmunity (IA) and type 1 diabetes (T1D). Our aim was to study the association of gluten intake with development of IA and progression to T1D, accounting for HLA genotype. Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of T1D based on presence of a first-degree relative with T1D, or HLA genotype. HLA genotypes were categorized in three groups as DR3/4 (DR3/4-DQ2/8), DR3 (DR3/3 or 3/X), and DR4 (DR4/4, 4/X or X/X, where X was neither 3 nor 4). Blood samples were collected at age 9, 15 and 24 months, and annually thereafter. IA was defined by the appearance of at least one autoantibody against insulin, IA-2, GAD or ZnT8 in at least two consecutive blood samples; T1D was defined using ADA criteria. Using FFQs we estimated the gluten intake (g/d) annually from 1 year of age. Cox regression was used to estimate hazard ratios adjusted for potential confounders. Results: This report includes 1,916 subjects followed from birth to the median age 13.5 y; 178 developed IA and 56 of these progressed to T1D. At the first assessment (median age 1.4 y) the average daily gluten intake was 11.4 g (SD: 5.6). The amount of gluten intake did not predict risk of IA (HR per 4 g 0.93; 95% CI 0.78-1.11) or progression from IA to T1D (HR 1.30; 95% CI 0.94-1.78). Four grams of gluten equal to a slice of bread. However, we found a significant interaction with HLA (p=0.02), where the association between gluten and IA were significantly different between all groups. Moreover, we found a significant interaction for progression to T1D (p=0.04) where in children with IA, gluten intake was associated with T1D among children with DR3/4 (HR 1.66 95% CI 1.10-2.51), but not in children with the other HLA groups. Conclusion: Gluten intake may have different effects on development of IA and progression from IA to T1D depending on HLA genotype.