title: Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus.
  
  
  METHODS
  A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study.
  
  
  RESULTS
  After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and β-cell function.
  
  
  CONCLUSIONS
  Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.
authors.affiliation: Metabolic and Cardiovascular Science Division, Department of Internal Medicine, San Raffaele Scientific Institute, Milan, Italy. monti.lucilla@hsr.it
authors.forename: L D
authors.initials: LD
authors.lastname: Monti
authors.forename: E
authors.initials: E
authors.lastname: Setola
authors.forename: P C G
authors.initials: PC
authors.lastname: Lucotti
authors.forename: M M
authors.initials: MM
authors.lastname: Marrocco-Trischitta
authors.forename: M
authors.initials: M
authors.lastname: Comola
authors.forename: E
authors.initials: E
authors.lastname: Galluccio
authors.forename: A
authors.initials: A
authors.lastname: Poggi
authors.forename: S
authors.initials: S
authors.lastname: Mammì
authors.forename: A L
authors.initials: AL
authors.lastname: Catapano
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: R
authors.initials: R
authors.lastname: Chiesa
authors.forename: E
authors.initials: E
authors.lastname: Bosi
authors.forename: P M
authors.initials: PM
authors.lastname: Piatti
mesh_terms: D000284:Administration, Oral; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D040242:Risk Reduction Behavior; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D001120:Arginine