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Effect of metformin on arginine and dimethylarginines in patients with advanced type 2 diabetes: A post hoc analysis of a randomized trial
- Source :
- Diabetes Obesity & Metabolism, 24(10), 1983-1988. Wiley, Diabetes, Obesity and Metabolism, 24(10), 1983-1988. Wiley
- Publication Year :
- 2022
-
Abstract
- AIM: To study the effect of metformin on plasma levels of arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), indicators of the nitric oxide pathway.MATERIALS AND METHODS: In this post hoc analysis of the HOME trial, we analysed plasma levels of arginine, ADMA and SDMA during the 4.3-year follow-up (comparing the effects of metformin versus placebo on top of insulin therapy). Statistical analysis was performed with a mixed model approach, in which simultaneously constant treatment effects were estimated, as well as time-dependent treatment effects.RESULTS: We found that metformin compared with placebo did not affect ADMA or SDMA plasma levels but rapidly decreased arginine plasma levels and hence the arginine to ADMA ratio. The constant treatment effect on ADMA was 0.99 (95% CI 0.97, 1.00) relative to placebo and the time-dependent treatment effect was 1.00 (95% CI 1.00, 1.01). By contrast, the constant treatment effect on arginine was 0.86 (95% CI 0.84, 0.88), with only a minimal time-dependent change of 1.01 (95% CI 1.00, 1.01).CONCLUSIONS: The potential benefits of metformin on endothelial function cannot be explained by a decrease in ADMA or by improved global arginine availability. The clinical significance of the decreased arginine plasma levels is not clear and can be harmful or beneficial, depending on the mechanism involved. However, a potential effect of metformin on the nitric oxide pathway is not restricted to the studied metabolites.
- Subjects :
- CITRULLINE
BIOAVAILABILITY
Endocrinology, Diabetes and Metabolism
ENDOTHELIAL FUNCTION
METABOLISM
Arginine
Nitric Oxide
INSULIN
DISEASE
DYSFUNCTION
Metformin
ADMA
INDIVIDUALS
Endocrinology
Diabetes Mellitus, Type 2
cardiovascular disease
Internal Medicine
randomized trial
Humans
type 2 diabetes
NITRIC-OXIDE SYNTHASE
Biomarkers
Subjects
Details
- ISSN :
- 14631326 and 14628902
- Volume :
- 24
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Diabetes, obesitymetabolismREFERENCES
- Accession number :
- edsair.doi.dedup.....12c4898b47ebc3c0bb31a1c8dba9fa4e