Plasma levels of Asymmetric Di Methyl Arginine and endothelial dysfunction in diabetic subjects with neuropathic foot ulcer

Abstract

ObjectiveAsymmetric dimethyl arginine (ADMA) is an amino acid that acts as an endogenous competitive inhibitor of Nitric oxide synthase, leading to endothelial dysfunction (ED). The aim of this study was to evaluate the relationship between plasma ADMA (p-ADMA) level and ED in diabetic subjects with neuropathic foot ulcer (NFU), and the possible predictors of p-ADMA level. Materials and methods80 diabetic subjects of matched age, sex and BMI were included; 40 with NFU (G1), 20 with peripheral nerve dysfunction (PND) (G2) and 20 without PND (G3), plus 20 matched healthy subjects (G4). Flow-mediated-dilatation (FMD) of brachial artery and Carotid-intima-media-thickness (CIMT) were measured to evaluate ED and subclinical atherosclerosis, respectively. ResultsG1&2 had a significantly lower FMD than G3&4 [−5.09 (−22.5 to 22.92), 4.67 (−15 to 23.91) vs. 15.74 (8.33−36.59) and 20.1 (10.0–46.15)%, respectively] (p < 0.001), and higher CIMT [0.9 (0.6–1.5), 0.9 (0.6–1.3) vs. 0.6 (0.5−0.8) and 0.7 (0.5−0.9) cm, respectively] (p < 0.001, r = 0.237, p = 0.034, r = 0.330, p = 0.003, respectively), with no significant correlation with FMD (r = −0.176, p = 0.118). FMD was inversely and strongly related to CIMT (r = −0.520, p < 0.001). p-ADMA levels were significantly higher in uncontrolled hypertensive patients in comparison to controlled and normotensive subjects [717 (286−3611) vs. 648 (335−874) and 686 (526−857) ng/L, respectively] (p = 0.026). Metformin users and hypertensive subjects on ACEIs or ARBs had the lowest p-ADMA levels than the non-users (p < 0.001, p = 0.007, respectively). ConclusionThe remarkable ED in diabetic subjects with NFU is unlikely to be due to alteration in p-ADMA. Further studies are needed in order to conclude a causal association between p-ADMA and ED in this group of patients.