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Changes in arginine are inversely associated with type 2 diabetes: A case‐cohort study in the PREDIMED trial
Author(s) -
Yu Edward,
RuizCanela Miguel,
Razquin Cristina,
GuaschFerré Marta,
Toledo Estefania,
Wang Dong D.,
Papandreou Christopher,
Dennis Courtney,
Clish Clary,
Liang Liming,
Bullo Monica,
Corella Dolores,
Fitó Montserrat,
GutiérrezBedmar Mario,
Lapetra José,
Estruch Ramón,
Ros Emilio,
Cofán Montserrat,
Arós Fernando,
Romaguera Dora,
SerraMajem Lluis,
Sorlí Jose V.,
SalasSalvadó Jordi,
Hu Frank B.,
MartínezGonzález Miguel A.
Publication year - 2019
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13514
Subject(s) - insulin resistance , asymmetric dimethylarginine , medicine , type 2 diabetes , ornithine , arginine , hazard ratio , confidence interval , endocrinology , cohort , diabetes mellitus , citrulline , gastroenterology , insulin , biology , biochemistry , amino acid
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.