Leena Hakola1, Maija E Miettinen1,2, Essi Syrjälä1, Mari Åkerlund1,2, Hanna-Mari Takkinen1,2, Tuuli E Korhonen2, Suvi Ahonen1,2,3, Jorma Ilonen4, Jorma Toppari5,6, Riitta Veijola7,8, Jaakko Nevalainen1, Mikael Knip9,10,11,12, Suvi M Virtanen1,2,3,13. 1. Faculty of Social Sciences, Health Sciences, Tampere University, Tampere, Finland. 2. Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland. 3. Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland. 4. Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland. 5. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland. 6. Department of Pediatrics, Turku University Hospital, Turku, Finland. 7. Department of Pediatrics, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland. 8. Oulu University Hospital, Oulu, Finland. 9. Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 10. Folkhälsan Research Center, Helsinki, Finland. 11. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 12. Department of Pediatrics, Tampere University Hospital, Tampere, Finland. 13. Center for Child Health Research, Tampere University, Tampere University Hospital, Tampere, Finland.
Abstract
IMPORTANCE: Dietary proteins, such as gluten, have been suggested as triggers of the disease process in type 1 diabetes (T1D). OBJECTIVE: To study the associations of cereal, gluten, and dietary fiber intake with the development of islet autoimmunity (IA) and T1D. DESIGN, SETTING, AND PARTICIPANTS: The prospective birth cohort Finnish Type 1 Diabetes Prediction and Prevention Study recruited children with genetic susceptibility to type 1 diabetes from September 1996 to September 2004 from 2 university hospitals in Finland and followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Altogether 6081 infants (78% of those invited) participated in the study. Dietary data were available for 5714 children (94.0%) and dietary and IA data were available for 5545 children (91.2%), of whom 3762 (68%) had data on islet autoantibodies up to age 6 years. Information on T1D was available for all children. Data were analyzed in 2018 and end point data were updated in 2015. EXPOSURES: Each child's intake of cereals, gluten, and dietary fiber was calculated from repeated 3-day food records up to 6 years. MAIN OUTCOMES AND MEASURES: Islet autoimmunity was defined as repeated positivity for islet cell antibodies and at least 1 biochemical autoantibody of 3 analyzed, or T1D. Data on the diagnosis of T1D were obtained from Finnish Pediatric Diabetes Register. RESULTS: Of 5545 children (2950 boys [53.2%]), 246 (4.4%) developed IA and of 5714 children (3033 boys [53.1%]), 90 (1.6%) developed T1D during the 6-year follow-up. Based on joint models, the intake of oats (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13), wheat (HR, 1.09; 95% CI, 1.03-1.15), rye (HR, 1.13; 95% CI, 1.03-1.23), gluten-containing cereals (HR, 1.07; 95% CI, 1.03-1.11), gluten without avenin from oats (HR, 2.23; 95% CI, 1.40-3.57), gluten with avenin (HR, 2.06; 95% CI, 1.45-2.92), and dietary fiber (HR, 1.41; 95% CI, 1.10-1.81) was associated with the risk of developing IA (HRs for 1 g/MJ increase in intake). The intake of oats (HR, 1.10; 95% CI, 1.00-1.21) and rye (HR, 1.20; 95% CI, 1.03-1.41) was associated with the risk of developing T1D. After multiple testing correction, the associations with IA remained statistically significant. CONCLUSIONS AND RELEVANCE: A high intake of oats, gluten-containing cereals, gluten, and dietary fiber was associated with an increased risk of IA. Further studies are needed to confirm or rule out the findings and study potential mechanisms.
IMPORTANCE: Dietary proteins, such as gluten, have been suggested as triggers of the disease process in type 1 diabetes (T1D). OBJECTIVE: To study the associations of cereal, gluten, and dietary fiber intake with the development of islet autoimmunity (IA) and T1D. DESIGN, SETTING, AND PARTICIPANTS: The prospective birth cohort Finnish Type 1 Diabetes Prediction and Prevention Study recruited children with genetic susceptibility to type 1 diabetes from September 1996 to September 2004 from 2 university hospitals in Finland and followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Altogether 6081 infants (78% of those invited) participated in the study. Dietary data were available for 5714 children (94.0%) and dietary and IA data were available for 5545 children (91.2%), of whom 3762 (68%) had data on islet autoantibodies up to age 6 years. Information on T1D was available for all children. Data were analyzed in 2018 and end point data were updated in 2015. EXPOSURES: Each child's intake of cereals, gluten, and dietary fiber was calculated from repeated 3-day food records up to 6 years. MAIN OUTCOMES AND MEASURES: Islet autoimmunity was defined as repeated positivity for islet cell antibodies and at least 1 biochemical autoantibody of 3 analyzed, or T1D. Data on the diagnosis of T1D were obtained from Finnish Pediatric Diabetes Register. RESULTS: Of 5545 children (2950 boys [53.2%]), 246 (4.4%) developed IA and of 5714 children (3033 boys [53.1%]), 90 (1.6%) developed T1D during the 6-year follow-up. Based on joint models, the intake of oats (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13), wheat (HR, 1.09; 95% CI, 1.03-1.15), rye (HR, 1.13; 95% CI, 1.03-1.23), gluten-containing cereals (HR, 1.07; 95% CI, 1.03-1.11), gluten without avenin from oats (HR, 2.23; 95% CI, 1.40-3.57), gluten with avenin (HR, 2.06; 95% CI, 1.45-2.92), and dietary fiber (HR, 1.41; 95% CI, 1.10-1.81) was associated with the risk of developing IA (HRs for 1 g/MJ increase in intake). The intake of oats (HR, 1.10; 95% CI, 1.00-1.21) and rye (HR, 1.20; 95% CI, 1.03-1.41) was associated with the risk of developing T1D. After multiple testing correction, the associations with IA remained statistically significant. CONCLUSIONS AND RELEVANCE: A high intake of oats, gluten-containing cereals, gluten, and dietary fiber was associated with an increased risk of IA. Further studies are needed to confirm or rule out the findings and study potential mechanisms.
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