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Diabetologia. 2018 Jul;61(7):1560-1571. doi: 10.1007/s00125-018-4611-5. Epub 2018 Apr 16.

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

Author information

1
Department of Preventive Medicine and Public Health, Facultad de Medicina, Universidad de Navarra, Irunlarrea 1, 31008, Pamplona, Spain. mcanela@unav.es.
2
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. mcanela@unav.es.
3
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. mcanela@unav.es.
4
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
5
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
6
Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain.
7
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
8
Department of Preventive Medicine and Public Health, Facultad de Medicina, Universidad de Navarra, Irunlarrea 1, 31008, Pamplona, Spain.
9
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
10
Broad Institute of MIT and Harvard University, Cambridge, MA, USA.
11
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
12
Department of Preventive Medicine, University of Valencia, Valencia, Spain.
13
Department of Internal Medicine, Biomedical Research Institute August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
14
Cardiovascular and Nutrition Research Group (Regicor Study Group), Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
15
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
16
Department of Preventive Medicine, University of Malaga, Malaga, Spain.
17
Department of Cardiology, University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
18
Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases, Mallorca, Spain.
19
Lipid Clinic, Department of Endocrinology and Nutrition Biomedical Research Institute August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
20
Department of Family Medicine, Research Unit, Primary Care Division of Sevilla, Sevilla, Spain.
21
Research Institute of Biomedical and Health Sciences and Medical School University of Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Spain.

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 ).

KEYWORDS:

Aromatic amino acids; Branched-chain amino acids; Mediterranean diet; Type 2 diabetes

PMID:
29663011
PMCID:
PMC5988977
[Available on 2019-07-01]
DOI:
10.1007/s00125-018-4611-5
[Indexed for MEDLINE]

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