Plasma metabolites associated with healthy Nordic dietary indexes and risk of type 2 diabetes-a nested case-control study in a Swedish population

Background: Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D. Objectives: We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort. Design: Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D. Results: In total, 31 metabolites were associated with BSDS and/or HNFI (-0.19 <= r <= 0.21, 0.10 <= ICC <= 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk. Conclusions: Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population