Gluten Intake and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in Children at Increased Risk of the Disease: The Diabetes Autoimmunity Study in the Young (DAISY)

Abstract

Objective: To study the association of gluten intake with development of islet autoimmunity and progression to type 1 diabetes.

Research design and methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of type 1 diabetes. Blood samples were collected at 9, 15, and 24 months of age, and annually thereafter. Islet autoimmunity was defined by the appearance of at least one autoantibody against insulin, IA2, GAD, or ZnT8 (zinc transporter 8) in at least two consecutive blood samples. Using food frequency questionnaires, we estimated the gluten intake (in grams per day) annually from 1 year of age. Cox regression modeling early gluten intake, and joint modeling of the cumulative gluten intake during follow-up, were used to estimate hazard ratios adjusted for confounders (aHR).

Results: By August 2017, 1,916 subjects were included (median age at end of follow-up 13.5 years), islet autoimmunity had developed in 178 participants, and 56 of these progressed to type 1 diabetes. We found no association between islet autoimmunity and gluten intake at 1-2 years of age or during follow-up (aHR per 4 g/day increase in gluten intake 1.00, 95% CI 0.85-1.17 and 1.01, 0.99-1.02, respectively). We found similar null results for progression from islet autoimmunity to type 1 diabetes. Introduction of gluten at <4 months of age was associated with an increased risk of progressing from islet autoimmunity to type 1 diabetes compared with introduction at 4-5.9 months (aHR 8.69, 95% CI 1.69-44.8).

Conclusions: Our findings indicate no strong rationale to reduce the amount of gluten in high-risk children to prevent development of type 1 diabetes.

Figure 1

Flow chart of the DAISY cohort. IA, islet autoimmunity; T1D, type 1 diabetes. *Cohort for joint modeling analyses was used in analyses of cumulative amount of gluten intake during follow-up and the risk of IA and progression from IA to T1D. †Cohort for Cox model analyses was used in analyses of age at the introduction of gluten, the amount of gluten intake at age 1–2 years, and the risk of IA and progression from IA to T1D.

Figure 2

Probability of islet autoimmunity (A) and progression to type 1 diabetes (B) according to tertiles for the amount of gluten intake at age 1–2 years. 1 = lowest third; 2 = middle third; 3 = highest third. When comparing subjects in the lowest third of gluten intake at age 1–2 years to those in the middle and highest third, we found no association with the risk of the development of islet autoimmunity or progression from islet autoimmunity to type 1 diabetes (all P values >0.47).