Decreased diabetes risk over 9 year after 18-month oral l-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of l-arginine study)

Abstract

PurposeThis study aimed to determine whether l-arginine supplementation lasting for 18 months maintained long-lasting effects on diabetes incidence, insulin secretion and sensitivity, oxidative stress, and endothelial function during 108 months among subjects at high risk of developing type 2 diabetes.MethodsOne hundred and forty-four middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an l-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. The primary outcome was a diagnosis of diabetes during the 108 month study period. Secondary outcomes included changes in insulin secretion (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress (AOPPs), and vascular function. After the 18 month participation, subjects that were still free of diabetes and willing to continue their participation (104 subjects) were further followed until diabetes diagnosis, with a time span of about 9 years from baseline.ResultsAlthough results derived from the 18 month of the intervention study demonstrated no differences in the probability of becoming diabetics, at the end of the study, the cumulative incidence of diabetes was of 40.6% in the l-arginine group and of 57.4% in the placebo group. The adjusted HR for diabetes (l-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP (p < 0.05) levels were ameliorated in l-arginine compared to placebo.ConclusionsThese results may suggest that the administration of l-arginine could delay the development of T2DM for a long period. This effect could be mediated, in some extent, by l-arginine-induced reduction in oxidative stress.

The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials

“…Subsequently, twenty-three full-text articles were carefully reviewed and eleven clinical trials were excluded because of the following reasons: five studies had a duration of supplementation period of less than 4 weeks; one study enrolled adolescents; two studies involved interventions that were a combination of other components together with L-arginine and the design did not enable evaluating L-arginine effect only; one study enrolled less than ten participants; and two articles reported the results from a same population. Finally, twelve trials (18,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) including fifteen treatment arms were considered eligible for the systematic review. However, one of the included articles (28) did not report the data required for the meta-analysis.…”

“…However, one of the included articles (28) did not report the data required for the meta-analysis. We contacted the corresponding author of the study twice but did not receive any response, and therefore it was subsequently, excluded, leaving eleven studies (18,(20)(21)(22)(23)(24)(25)(26)(27)29,30) for inclusion in the meta-analysis.…”

“…In total, 631 participants were enrolled in the selected articles, out of which 359 individuals were allocated to L-arginine supplementation group and 272 subjects to the control group. These studies were published between 1996 and 2019 and were carried out in the Iran (20)(21)(22)(23)29) , Italy (27) , Poland (18,24,26) , Israel (28) , UK (30) and Germany (25) . All studies except two (28,30) adopted a parallel study design.…”

“…In these studies, the daily supplementation dosage of L-arginine varied between 1 and 21 g/d. The health status of the included participants was mixed and included type 2 diabetes patients (22) , postmenopausal women (28) , patients with CVD (26) , subjects with hypercholesterolaemia (30) , obese individuals (18,20,24,29) , subjects with hypertriacylglycerolaemia (25) , individuals with the metabolic syndrome (23) , healthy subjects (21) and those with impaired glucose tolerance and the metabolic syndrome (27) . No major adverse effects attributable to intervention or control were reported in RCT.…”

“…Several trials investigated the potential of L-arginine supplementation for the treatment of abnormal lipid profile; however, the results are inconsistent. For instance, some trials report that L-arginine supplementation induced a reduction in circulating concentrations of lipid parameters (20)(21)(22)(23) , while others report no significant effect (18,(24)(25)(26)(27)(28)(29)(30) . Discrepancies in the findings may conceivably be attributed to the differences in study designs, characteristics of study participants, duration and the supplementation dosage applied in the trials.…”