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Diabetes Obes Metab. 2019 Feb;21(2):397-401. doi: 10.1111/dom.13514. Epub 2018 Oct 2.

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

Author information

1
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
2
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
3
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
4
Medicina Preventiva y Salud Pública, IdiSNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain.
5
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
6
Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
7
Broad Institute of MIT and Harvard University, Cambridge, Massachusetts.
8
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
9
Department of Preventive Medicine, University of Valencia, Valencia, Spain.
10
Department of Preventive Medicine, University of Málaga, Málaga, Spain.
11
Department of Family Medicine, Unit Research, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain.
12
Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
13
Lipid Clinic, Department of Endocrinology and Nutrition, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
14
Department of Cardiology, University Hospital of Álava, Vitoria, Spain.
15
Epidemiología Clínica y Salud Pública, Health Research Institute of Palma (IdISPa), University Hospital Son Espases, Palma de Mallorca, Spain.
16
Department of Clinical Sciences, Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
17
Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Massachusetts.

Abstract

The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.

KEYWORDS:

cohort study; dietary intervention; insulin resistance; observational study; population study, type 2 diabetes

PMID:
30146690
PMCID:
PMC6329637
[Available on 2020-02-01]
DOI:
10.1111/dom.13514

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