Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Ruiz-Canela, Miguel; Hernáez, Álvaro; Fitó Colomer, Montserrat; Martínez-González, Miguel Ángel, 1957-

doi:http://dx.doi.org/10.1007/s00125-018-4611-5

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Citation

Ruiz-Canela M, Guasch-Ferré M, Toledo E, Clish CB, Razquin C, Liang L et al. Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial. Diabetologia. 2018 Jul;61(7):1560-71. DOI: 10.1007/s00125-018-4611-5

Abstract

Aims/hypothesis: Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. Methods: We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. Results: Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD = 1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p = 0.005 vs the control group). Conclusions/interpretation: Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence. Clinical trial number: SRCTN35739639 ( www.controlled-trials.com ).