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

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.

• Authors: Edward Yu, Miguel Ruiz-Canela, Cristina Razquin, Marta Guasch-Ferré, Estefania Toledo, Dong D Wang, Christopher Papandreou, Courtney Dennis, Clary Clish, Liming Liang, Monica Bullo, Dolores Corella, Montserrat Fitó, Mario Gutiérrez-Bedmar, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Dora Romaguera, Lluis Serra-Majem, Jose V Sorlí, Jordi Salas-Salvadó, Frank B Hu, Miguel A Martínez-González
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 21 Issue 2 Pg. 397-401 (02 2019) ISSN: 1463-1326 [Electronic] England
• PMID: 30146690 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• omega-N-Methylarginine
• Citrulline
• symmetric dimethylarginine
• N,N-dimethylarginine
• Arginine
• Ornithine

Topics

• Aged
• Aged, 80 and over
• Arginine (analogs & derivatives, blood)
• Case-Control Studies
• Citrulline (blood)
• Cohort Studies
• Diabetes Mellitus, Type 2 (blood, epidemiology, pathology)
• Diet, Fat-Restricted (statistics & numerical data)
• Diet, Mediterranean (statistics & numerical data)
• Female
• Humans
• Incidence
• Insulin Resistance (physiology)
• Male
• Middle Aged
• Ornithine (blood)
• Risk Factors
• omega-N-Methylarginine (blood)