%0 Journal Article %A Jäger, Susanne %A Kuxhaus, Olga %A Prada, Marcela %A Huybrechts, Inge %A Tong, Tammy Y N %A Forouhi, Nita G %A Razquin, Cristina %A Corella, Dolores %A Martinez-Gonzalez, Miguel A %A Dahm, Christina C %A Ibsen, Daniel B %A Tjønneland, Anne %A Halkjær, Jytte %A Marques, Chloé %A Cadeau, Claire %A Ren, Xuan %A Katzke, Verena %A Bendinelli, Benedetta %A Agnoli, Claudia %A Catalano, Alberto %A Farràs, Marta %A Sánchez, Maria-Jose %A López, María Dolores Chirlaque %A Guevara, Marcela %A Aune, Dagfinn %A Sharp, Stephen J %A Wareham, Nicholas J %A Schulze, Matthias B %T Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies. %J BMC medicine %V 23 %N 1 %@ 1741-7015 %C London %I BioMed Central %M DKFZ-2025-01175 %P 344 %D 2025 %X Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels-reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial.In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1.In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95 %K Humans %K Diabetes Mellitus, Type 2: genetics %K Diabetes Mellitus, Type 2: blood %K Diabetes Mellitus, Type 2: epidemiology %K Fatty Acid Desaturases: genetics %K Delta-5 Fatty Acid Desaturase %K alpha-Linolenic Acid: administration & dosage %K Male %K Female %K Linoleic Acid: administration & dosage %K Linoleic Acid: blood %K Middle Aged %K Aged %K Nuts %K Fatty Acids: blood %K Cohort Studies %K Polymorphism, Single Nucleotide %K Risk Factors %K Cohort study (Other) %K Fatty acid desaturase (Other) %K Plasma phospholipid fatty acids (Other) %K Polyunsaturated fatty acids (Other) %K Randomized controlled trial (Other) %K Fatty Acid Desaturases (NLM Chemicals) %K Delta-5 Fatty Acid Desaturase (NLM Chemicals) %K FADS1 protein, human (NLM Chemicals) %K alpha-Linolenic Acid (NLM Chemicals) %K Linoleic Acid (NLM Chemicals) %K Fatty Acids (NLM Chemicals) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:40484934 %R 10.1186/s12916-025-04187-8 %U https://inrepo02.dkfz.de/record/301905