Elevated asymmetric dimethylarginine in plasma: an early marker for endothelial dysfunction in non-alcoholic fatty liver disease?

Abstract

Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease. Asymmetric dimethylarginine (ADMA) is a novel marker of endothelial dysfunction and atherosclerosis. We aimed to investigate circulating ADMA concentrations in biopsy proven NAFLD and also to search its association with carotid atherosclerosis.

Methods: Sixty-seven nondiabetic and normotensive patients with NAFLD and 35 healthy controls were enrolled. Plasma ADMA was measured along with glucose, lipids and insulin levels. Insulin resistance (IR) was assessed by homeostasis model assessment-estimated insulin resistance (HOMA-IR) method. Carotid atherosclerosis was evaluated by carotid artery intima-media thickness (CIMT) using carotid ultrasonography.

Results: ADMA levels and CIMT measurements were significantly higher in NAFLD group than the controls. However, the difference regarding the CIMT disappeared when the findings were adjusted according to the metabolic parameters and insulin sensitivity. In contrast, the difference for ADMA remained significant between two groups. No significant association was found between ADMA, CIMT and histopathological findings.

Conclusions: Plasma ADMA levels are increased in subjects with NAFLD. This increase seems to be independent from traditional cardiovascular risk factors, insulin resistance and liver histology. Circulating ADMA may be an earlier marker of vascular damage with respect to CIMT in subjects with NAFLD.