Erythrocyte membrane docosapentaenoic acid levels are associated with islet autoimmunity: the Diabetes Autoimmunity Study in the Young

Abstract

Aims/hypotheses We previously reported that lower n-3 fatty acid intake and levels in erythrocyte membranes were associated with increased risk of islet autoimmunity (IA) but not progression to type 1 diabetes in children at increased risk for diabetes. We hypothesise that specific n-3 fatty acids and genetic markers contribute synergistically to this increased risk of IA in the Diabetes Autoimmunity Study in the Young (DAISY). Methods DAISY is following 2547 children at increased risk for type 1 diabetes for the development of IA, defined as being positive for glutamic acid decarboxylase (GAD)65, IA-2 or insulin autoantibodies on two consecutive visits. Using a case-cohort design, erythrocyte membrane fatty acids and dietary intake were measured prospectively in 58 IA-positive children and 299 IA-negative children. Results Lower membrane levels of the n-3 fatty acid, docosapentaenoic acid (DPA), were predictive of IA (HR 0.23; 95% CI 0.09,0.55), while alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not, adjusting for HLA and diabetes family history. We examined whether the effect of dietary intake of the n-3 fatty acid ALA on IA risk was modified by fatty acid elongation and desaturation genes. Adjusting for HLA, diabetes family history, ethnicity, energy intake and questionnaire type, ALA intake was significantly more protective for IA in the presence of an increasing number of minor alleles at FADS1 rs174556 (pinteraction=0.017), at FADS2 rs174570 (pinteraction=0.016) and at FADS2 rs174583 (pinteraction=0.045). Conclusions/interpretation The putative protective effect of n-3 fatty acids on IA may result from a complex interaction between intake and genetically-controlled fatty acid desaturation.

Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity

“…Furthermore, the prospective Diabetes Autoimmunity Study in the Young (DAISY), investigating older children (9 months to 8 years of age), found that high dietary intake and erythrocyte membrane content of n-3 PUFAs were associated with a decreased risk of islet autoimmunity (defined as repeated positivity for at least one autoantibody) [10,11], but not with progression to type 1 diabetes [13]. Results from DAISY as well as the DIPP cohort support the view that early stages of autoimmunity are affected by long-chain n-3 PUFAs.…”

“…Long-chain n-3 polyunsaturated fatty acid (PUFA) intake and/or status were protectively related to type 1 diabetes-associated autoimmunity or clinical disease in several [9][10][11], but not all [12,13], epidemiological studies. Maternal intake and status of fish-derived fatty acids during pregnancy were not associated with the risk of developing type 1 diabetes in the offspring [9,14,15], with the exception of one case-control study reporting a protective association [16].…”

Dietary factors in the development of type 1 diabetes

“…A child's serum proportion of dairy-associated fatty acids was related to an increased risk of advanced islet autoimmunity at or closest to the time of seroconversion, whereas that of linoleic acid conferred a lower risk (29). Fatty acid desynthetase (FADS) genes could interact with αlinolenic acid intake, resulting in a protective effect against islet autoimmunity in children with higher number of minor alleles of these genes (66).…”

Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study

“…According to these studies, the benefit of n‐3 FA may be in the inhibition of IA seroconversion. More recently, the DAISY Study has shown a reduced risk for IA in children who consume alpha‐linoleic acid rich foods and supplements and have a specific genetic variant in FA desaturation …”