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Land Cover of Early Life Environment Modulates the Risk of Type 1 Diabetes

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posted on 05.05.2021, 18:35 by Noora Nurminen, Damiano Cerrone, Jussi Lehtonen, Anirudra Parajuli, Marja Roslund, Maria Lönnrot, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Mikael Knip, Juho Rajaniemi, Olli H. Laitinen, Aki Sinkkonen, Heikki Hyöty
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 in order 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 CORINE 2012 and 2000 data around the dwelling during the first year of life for 10681 children genotyped for disease associated HLA-DQ alleles and followed from birth in the DIPP study. Land cover was compared between children who developed type 1 diabetes (N=271) or multiple diabetes-associated islet autoantibodies (N=384) and non-diabetic autoantibody negative children.

RESULTS

Agricultural land cover around the home was inversely associated with diabetes risk (OR 0.37, 95% CI 0.16-0.87, P = 0.02 within a distance of 1500 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 microbial community indoors leading to reduced bacterial richness and diversity indoors which might explain the regional difference in the association. In survival models, agricultural environment was associated with a decreased risk of multiple islet autoantibodies (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 to urban environment known to have lower environmental microbial diversity.

CONCLUSIONS

The study suggests that exposure to agricultural environment (comprising non-irrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agro-forestry 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.

Funding

This work is supported by the Finnish Funding Agency for Innovation TEKES under the Large Strategic Opening project ‘ADELE’ (grant number 40333/14) and HiLIFE Proof of Concept grant. This work and the DIPP study is additionally supported by JDRF (grants 1-SRA-2016-342-M-R, 1-SRA-2019-732-M-B); Novo Nordisk Foundation; Academy of Finland (Decision No 292538 and Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017, Decision No. 250114); Special Research Funds for University Hospitals in Finland; Sigrid Juselius Foundation and the Diabetes Research Foundation in Finland.

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