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

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

  • Yu, E
  • Ruiz-Canela, M
  • Razquin, C
  • Guasch-Ferré, M
  • Toledo, E
  • Wang, DD
  • Papandreou, C
  • Dennis, C
  • Clish, C
  • Liang, L
  • Bullo, M
  • Corella, D
  • Fitó, M
  • Gutiérrez-Bedmar, M
  • Lapetra, J
  • Estruch, R
  • Ros, E
  • Cofán, M
  • Arós, F
  • Romaguera, D
  • Serra-Majem, L
  • Sorlí, JV
  • Salas-Salvadó, J
  • Hu, FB
  • Martinez-Gonzalez, Miguel A

publication date

  • 2019