Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity
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We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk.
We performed a nested case–control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate <0.05.
Serum fatty acid composition differed between breastfed and non-breastfed infants, reflecting differences in the fatty acid composition of the milk. Fatty acids were associated with islet autoimmunity (higher serum pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids decreased risk; higher arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Furthermore, fatty acids were associated with primary insulin autoimmunity, these associations being stronger (higher palmitoleic acid, cis-vaccenic, arachidonic, docosapentaenoic and docosahexaenoic acids decreased risk; higher α-linoleic acid and arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Moreover, the quantity of breast milk consumed per day was inversely associated with primary insulin autoimmunity, while the quantity of cow’s milk consumed per day was directly associated.
Fatty acid status may play a role in the development of type 1 diabetes-associated autoimmunity. Fish-derived fatty acids may be protective, particularly during infancy. Furthermore, fatty acids consumed during breastfeeding may provide protection against type 1 diabetes-associated autoimmunity. Further studies are warranted to clarify the independent role of fatty acids in the development of type 1 diabetes.
KeywordsAutoimmunity Breast milk Fatty acid status Infant n-3 fatty acids Type 1 diabetes
Conjugated linoleic acid
Type 1 diabetes prediction and prevention study
False discovery rate
Autoantibodies to 65 kDa isoform of GAD
Antibodies to tyrosine phosphatase-related islet antigen 2
Islet cell autoantibodies
Monounsaturated fatty acid
Polyunsaturated fatty acid
Saturated fatty acid
We express our gratitude to the children and parents who participated. We thank the DIPP research nurses, doctors, nutritionists and laboratory staff in the University Hospitals of Oulu and Tampere, Faculty of Social Sciences of the University of Tampere and the Nutrition Unit in the National Institute for Health and Welfare for excellent collaboration over the years. I. Salminen (Public Health Solutions, National Institute for Health and Welfare, Finland) is gratefully acknowledged for scientific advice and assistance during fatty acid analysis.
The datasets generated during and/or analysed during the current study are not publicly available due to the protection of the identity of the study participants and their clinical data, but data is available from the corresponding author on reasonable request.
This work was supported by the Academy of Finland (Grants 63672, 68292, 79685, 79686, 80846, 114666, 126813, 129492, 139391, 201988, 210632, 276475), European Foundation for the Study of Diabetes (EFSD/Novo Nordisk Partnership and EFSD/JDRF/Novo Nordisk Programme), the Juho Vainio Foundation, the Yrjö Jahnsson Foundation, the Competitive State Research Financing of the Expert Responsibility area of Tampere, Turku and Oulu University Hospitals (Grants 9E082, 9F089, 9G087, 9H092, 9J147, 9K149, 9L042, 9L117, 9M036, 9M114, 9N086, 9P057, 9R055, 9S074), the JDRF (grants 4-1998-274, 4-1999-731, 4-2001-435), the European Union (grant BMH4-CT98-3314), the Novo Nordisk Foundation, the Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012–2017, Decision No. 250114) and the Sigrid Juselius Foundation. The study sponsors were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
All authors were responsible for the study concept and design, acquisition of data and analysis or interpretation of the data. SN, IE, OV and SMV researched data. IE supervised serum fatty acid analyses. H-MT performed statistical analysis. SA supervised dietary data collection, processing and analysis. JT, RV and MK provided the clinical data used in this study and supervised the clinical work. RV and MK were responsible for the autoantibody analyses and JI for the genetic analyses. SN wrote the first version of the manuscript. IE contributed significantly to the writing and revision of the manuscript. SMV reviewed the manuscript. All authors edited the manuscript. All authors have approved the final version to be published. SMV is the guarantor of this work and, as such had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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