Noora Nurminen1, Damiano Cerrone2, Jussi Lehtonen1, Anirudra Parajuli3, Marja Roslund3, Maria Lönnrot1,4, Jorma Ilonen5,6, Jorma Toppari7,8, Riitta Veijola9, Mikael Knip10,11,12,13, Juho Rajaniemi2, Olli H Laitinen1, Aki Sinkkonen3,14, Heikki Hyöty15,16. 1. Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. 2. Faculty of Built Environment, Tampere University, Tampere, Finland. 3. Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland. 4. Department of Dermatology, Tampere University Hospital, Tampere, Finland. 5. Institute of Biomedicine, University of Turku, Turku, Finland. 6. Clinical Microbiology, Turku University Hospital, Turku, Finland. 7. Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland. 8. Department of Pediatrics, Turku University Hospital, Turku, Finland. 9. Department of Pediatrics, University of Oulu and Oulu University Hospital, Oulu, Finland. 10. Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 11. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 12. Folkhälsan Research Center, Helsinki, Finland. 13. Department of Pediatrics, Tampere University Hospital, Tampere, Finland. 14. Natural Resources Institute Finland Luke, Turku, Finland. 15. Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland heikki.hyoty@tuni.fi. 16. Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
Abstract
OBJECTIVE: Environmental microbial exposures have been implicated to protect against immune-mediated diseases such as type 1 diabetes. Our objective was to study the association of land cover around the early-life dwelling with the development of islet autoimmunity and type 1 diabetes to evaluate the role of environmental microbial biodiversity in the pathogenesis. RESEARCH DESIGN AND METHODS: Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease-associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies. RESULTS: Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16-0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity. CONCLUSIONS: The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry areas) early in life is inversely associated with the risk of type 1 diabetes. This association may be mediated by early exposure to environmental microbial diversity.
OBJECTIVE: Environmental microbial exposures have been implicated to protect against immune-mediated diseases such as type 1 diabetes. Our objective was to study the association of land cover around the early-life dwelling with the development of islet autoimmunity and type 1 diabetes to evaluate the role of environmental microbial biodiversity in the pathogenesis. RESEARCH DESIGN AND METHODS: Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease-associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies. RESULTS: Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16-0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity. CONCLUSIONS: The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry areas) early in life is inversely associated with the risk of type 1 diabetes. This association may be mediated by early exposure to environmental microbial diversity.
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