TY - JOUR
T1 - Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes
T2 - case-cohort study within the PREDIMED Trial
AU - Ruiz-Canela, Miguel
AU - Guasch-Ferré, Marta
AU - Toledo, Estefanía
AU - Clish, Clary B.
AU - Razquin, Cristina
AU - Liang, Liming
AU - Wang, Dong D.
AU - Corella, Dolores
AU - Estruch, Ramón
AU - Hernáez, Álvaro
AU - Yu, Edward
AU - Gómez-Gracia, Enrique
AU - Zheng, Yan
AU - Arós, Fernando
AU - Romaguera, Dora
AU - Dennis, Courtney
AU - Ros, Emilio
AU - Lapetra, José
AU - Serra-Majem, Lluis
AU - Papandreou, Christopher
AU - Portoles, Olga
AU - Fitó, Montserrat
AU - Salas-Salvadó, Jordi
AU - Hu, Frank B.
AU - Martínez-González, Miguel A.
N1 - Funding Information:
Funding This study was supported by research grant NIDDK-R01DK 102896 from the National Institutes of Health. EY was supported with the grant F31 DK114938-01. MG-F was supported by EFSD (European Foundation for the Study of Diabetes)/Lilly through the Institut d’Investigacions Sanitàries Pere i Virgili (IISPV). CP was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016–2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428).
Funding Information:
We are very grateful to all the participants for their enthusiastic collaboration, the PREDIMED personnel for their excellent assistance, and the personnel of all affiliated primary care centres. CIBEROBN is an initiative of Instituto de Salud Carlos III, Spain. MR-C and MAM-G conducted the statistical analyses and drafted the article. MR-C, FBH, ET, CBC, LL, JS-S, and MAM-G made substantial contributions to the conception and design of the work. All authors contributed substantially in the acquisition of data or analysis and interpretation of data. All authors revised the article critically for important intellectual content. All authors approved the version to be published. ER has received honoraria for lectures and grants for research through his institution from the California Walnut Commission and is a nonpaid member of its Scientific Advisory Committee. JS-S has received grants for research through his institution from the International Nut and Dried Fruit Council and is a nonpaid member of its Scientific Advisory Committee. The rest of the authors declare that there is no duality of interest associated with this manuscript.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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).
AB - 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).
KW - Aromatic amino acids
KW - Branched-chain amino acids
KW - Mediterranean diet
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85045441217&partnerID=8YFLogxK
U2 - 10.1007/s00125-018-4611-5
DO - 10.1007/s00125-018-4611-5
M3 - Article
C2 - 29663011
AN - SCOPUS:85045441217
SN - 0012-186X
VL - 61
SP - 1560
EP - 1571
JO - Diabetologia
JF - Diabetologia
IS - 7
ER -
