Changes in Arginine Are Inversely Associated With Type 2 Diabetes: A Case-Cohort Study in the PREDIMED Trial

Diabetes Obes Metab. 2019 Feb;21(2):397-401. doi: 10.1111/dom.13514. Epub 2018 Oct 2.

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.

Keywords: cohort study; dietary intervention; insulin resistance; observational study; population study, type 2 diabetes.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives
  • Arginine / blood*
  • Case-Control Studies
  • Citrulline / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / 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

Substances

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