Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study

Sari Niinistö, Maija E Miettinen, David Cuthbertson, Jarno Honkanen, Leena Hakola, Reija Autio, Iris Erlund, Petra Arohonka, Arja Vuorela, Taina Härkönen, Heikki Hyöty, Jeffrey P Krischer, Outi Vaarala, Mikael Knip, Suvi M Virtanen, TRIGR Investigators, Sari Niinistö, Maija E Miettinen, David Cuthbertson, Jarno Honkanen, Leena Hakola, Reija Autio, Iris Erlund, Petra Arohonka, Arja Vuorela, Taina Härkönen, Heikki Hyöty, Jeffrey P Krischer, Outi Vaarala, Mikael Knip, Suvi M Virtanen, TRIGR Investigators

Abstract

Aims: Altered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity.

Methods: Serum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers.

Results: Correlations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations.

Conclusions: In cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored.

Trial registry number: NCT00179777.

Keywords: chemokines; children; cytokines; fatty acids; growth factors; immunological markers; islet autoimmunity; type 1 diabetes.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Niinistö, Miettinen, Cuthbertson, Honkanen, Hakola, Autio, Erlund, Arohonka, Vuorela, Härkönen, Hyöty, Krischer, Vaarala, Knip, Virtanen and TRIGR Investigators.

Figures

Figure 1
Figure 1
Spearman correlation coefficients between serum fatty acids and immunological markers separately in case and in control children in cord serum, and at the ages of 6 and 12 months. All the direct correlations are marked with red edges, while the inverse correlations are marked with blue edges with a cutoff of p < 0.01.

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