Plasma Metabolite Profiles Associated with the Amount and Source of Meat and Fish Consumption and the Risk of Type 2 Diabetes

Scope: Consumption of meat has been associated with a higher risk of type 2 diabetes (T2D), but if plasma metabolite profiles associated with these foods reflect this relationship is unknown. The objective is to identify a metabolite signature of consumption of total meat (TM), red meat (RM), processed red meat (PRM), and fish and examine if they are associated with T2D risk. Methods and results: The discovery population includes 1833 participants from the PREDIMED trial. The internal validation sample includes 1522 participants with available 1-year follow-up metabolomic data. Associations between metabolites and TM, RM, PRM, and fish are evaluated with elastic net regression. Associations between the profiles and incident T2D are estimated using Cox regressions. The profiles included 72 metabolites for TM, 69 for RM, 74 for PRM, and 66 for fish. After adjusting for T2D risk factors, only profiles of TM (Hazard Ratio (HR): 1.25, 95% CI: 1.06-1.49), RM (HR: 1.27, 95% CI: 1.07-1.52), and PRM (HR: 1.27, 95% CI: 1.07-1.51) are associated with T2D. Conclusions: The consumption of TM, its subtypes, and fish is associated with different metabolites, some of which have been previously associated with T2D. Scores based on the identified metabolites for TM, RM, and PRM show a significant association with T2D risk. The PREDIMED study was funded by NIH grants R01 HL118264 and R01 DK102896 and by the Spanish Ministry of Health (Instituto de Salud Carlos III, The PREDIMED Network grant RD 06/0045, 2006–2013, coordinated by MAM-G; and a previous network grant RTIC-G03/140, 2003–2005, coordinated R. Estruch). Additional grants were received from the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304, and AGL2010-22319-C03-03) and the Generalitat Valenciana (ACOMP2010-181, AP-111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159, ACOMP/213/165, and PROMETEO17/2017). M.G.-F. is supported by R21AG070375-01A1. J.S.-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program. I.P.-G. receives a grant from the Ministerio de Ciencia, Innovación y Universidades (MICINN) (FPU 17/01925). S.K.N. gratefully acknowledges support from a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR, MFE-171207).