Yu, EdwardRuiz-Canela, MiguelRazquin, CristinaGuasch-Ferré, MartaToledo, EstefaniaWang, Dong DPapandreou, ChristopherDennis, CourtneyClish, ClaryLiang, LimingBullo, MonicaCorella, DoloresFitó, MontserratGutiérrez-Bedmar, MarioLapetra, JoséEstruch, RamónRos, EmilioCofán, MontserratArós, FernandoRomaguera, DoraSerra-Majem, LluisSorlí, Jose VSalas-Salvadó, JordiHu, Frank BMartínez-González, Miguel A2023-01-252023-01-252018-10-02http://hdl.handle.net/10668/12873The 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.encohort studydietary interventioninsulin resistanceobservational studypopulation study, type 2 diabetesAgedAged, 80 and overArginineCase-Control StudiesCitrullineCohort StudiesDiabetes Mellitus, Type 2Diet, Fat-RestrictedDiet, MediterraneanFemaleHumansIncidenceInsulin ResistanceMaleMiddle AgedOrnithineRisk Factorsomega-N-Methylarginineresearch article30146690open access10.1111/dom.135141463-1326PMC6329637https://europepmc.org/articles/pmc6329637?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329637/pdf