Plasma metabolomic profiling of dietary patterns associated with glucose metabolism status:The Maastricht Study

BACKGROUND: Glucose metabolism has been reported to be affected by dietary patterns, while the underlying mechanisms involved remain unclear. This study aimed to investigate the potential mediation role of circulating metabolites in relation to dietary patterns for prediabetes and type 2 diabetes.METHODS: Data was derived from The Maastricht Study that comprised of 3441 participants (mean age of 60 years) with 28% type 2 diabetes patients by design. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ), and the glucose metabolism status (GMS) was defined according to WHO guidelines. Both cross-sectional and prospective analyses were performed for the circulating metabolome to investigate their associations and mediations with responses to dietary patterns and GMS.RESULTS: Among 226 eligible metabolite measures obtained from targeted metabolomics, 14 were identified to be associated and mediated with three dietary patterns (i.e. Mediterranean Diet (MED), Dietary Approaches to Stop Hypertension Diet (DASH), and Dutch Healthy Diet (DHD)) and overall GMS. Of these, the mediation effects of 5 metabolite measures were consistent for all three dietary patterns and GMS. Based on a 7-year follow-up, a decreased risk for apolipoprotein A1 (APOA1) and docosahexaenoic acid (DHA) (RR 0.60, 95% CI 0.55, 0.65; RR 0.89, 95% CI 0.83, 0.97, respectively) but an increased risk for ratio of ω-6 to ω-3 fatty acids (RR 1.29, 95% CI 1.05, 1.43) of type 2 diabetes were observed from prediabetes, while APOA1 showed a decreased risk of type 2 diabetes from normal glucose metabolism (NGM; RR 0.82, 95% CI 0.75, 0.89).CONCLUSIONS: In summary, this study suggests that adherence to a healthy dietary pattern (i.e. MED, DASH, or DHD) could affect the GMS through circulating metabolites, which provides novel insights into understanding the biological mechanisms of diet on glucose metabolism and leads to facilitating prevention strategy for type 2 diabetes.