6533b82cfe1ef96bd128f6f8

RESEARCH PRODUCT

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

Miguel ÁNgel Martínez-gonzálezMiguel ÁNgel Martínez-gonzálezLiming LiangJosé LapetraDolores CorellaDolores CorellaMario Gutiérrez-bedmarEdward YuDong D. WangRamon EstruchRamon EstruchJosé V SorlíJosé V. SorlíMontserrat CofánMontserrat CofánMarta Guasch-ferréMarta Guasch-ferréMarta Guasch-ferréMiguel Ruiz-canelaMiguel Ruiz-canelaFrank B. HuFrank B. HuCourtney DennisMontserrat FitóMontserrat FitóMònica BullóCristina RazquinLluis Serra-majemLluis Serra-majemJordi Salas-salvadóJordi Salas-salvadóFernando ArósClary B. ClishDora RomagueraEstefanía ToledoEstefanía ToledoChristopher PapandreouEmilio RosEmilio Ros

subject

MaleOrnithineArginineEndocrinology Diabetes and MetabolismType 2 diabetes030204 cardiovascular system & hematologyDiet MediterraneanCohort Studieschemistry.chemical_compound0302 clinical medicineEndocrinologyRisk FactorsObservational studyCitrullineDiet Fat-RestrictedAged 80 and overIncidenceType 2 diabetesMiddle AgedOrnithineHomeostatic model assessmentFemaleCohort studyPopulation studymedicine.medical_specialtypopulation study type 2 diabetes030209 endocrinology & metabolismArginineArticle03 medical and health sciencesInsulin resistanceDiabetes mellitusInternal medicineInternal MedicinemedicineHumansAgedomega-N-Methylargininebusiness.industryInsulin resistancemedicine.diseaseDietary interventionEndocrinologyDiabetes Mellitus Type 2chemistryCase-Control StudiesCitrullineAsymmetric dimethylargininebusiness

description

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.

yearjournalcountryeditionlanguage
2018-10-02
10.1111/dom.13514http://hdl.handle.net/10261/213128