Abstract 022: Plasma Metabolome Related To Plant-based Diets And The Association With Type 2 Diabetes: A Prospective Cohort Study

Background: Plant-based diets have been associated with a lower risk of type 2 diabetes. However, the underlying mechanisms are not completely understood, and the evidence using objective approaches to assess the adherence of plant-based diets is limited. Methods: In the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study, we characterized the plasma metabolome related to plant-based diets and examined its association with the incidence of type 2 diabetes among 10 699 participants. Plasma metabolomic profiling was conducted by liquid chromatography-tandem mass spectrometry. Adherence to plant-based diets was assessed by three plant-based diet indices derived from the food frequency questionnaire: an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI). Metabolomic signatures reflecting the adherence to plant-based diets were created using elastic net regression, and their associations with risk of type 2 diabetes were subsequently evaluated using multivariable Cox proportional hazards regression. Results: Among 263 metabolites measured, nearly half were significantly associated with PDI (41.4%, 109 of 263), hPDI (51.7%, 136 of 263), and uPDI (40.3%, 106 of 263) after Bonferroni correction. We developed a metabolomic signature comprising 53 metabolites for PDI, 76 metabolites for hPDI, and 88 metabolites for uPDI, each robustly correlated with the corresponding diet index (r=0.34-0.36 for PDI, 0.43-0.44 for hPDI, and 0.36-0.37 for uPDI). We observed an inverse association of PDI metabolomic signature (HR 0.86, 95% CI 0.79-0.93 per one standard deviation) and hPDI metabolomic signature (0.79, 0.72-0.86) with type 2 diabetes risk after adjustment for body mass index and other potential confounders. These two inverse associations remained significant even further adjusting for the corresponding diet index PDI and hPDI. The metabolomic signature for uPDI was not associated with type 2 diabetes risk (1.00, 0.93-1.09). Conclusion: Plasma metabolome can robustly reflect adherence and metabolic response to plant-based diets. Metabolomic signatures reflecting greater adherence to an overall plant-based diet, especially a healthful plant-based diet, were associated with a lower risk of type 2 diabetes. These findings support and provide mechanistic insights on the important role of healthful plant-based diets in diabetes prevention.