PLASMA LEVELS OF ASYMMETRIC DI METHYL ARGININE IN DIABETIC PATIENTS WITH NEUROPATHIC FOOT ULCERATION

Abstract

Background. Increased cardiovascular mortality had been reported in diabetic subjects with neuropathic foot ulceration (NFU). Endothelial dysfunction (ED) was found to be more remarkable in diabetic subjects with NFU than those without peripheral nerve dysfunction (PND) which could explain the excess cardiovascular morbidity and mortality. By inhibiting nitric oxide (NO) formation, Asymmetric dimethylarginine (ADMA) was found to cause ED.
Aim of the work. To evaluate plasma ADMA level as a marker of ED in diabetic subjects with NFU, and to study the possible relations of plasma ADMA level with ED and atherosclerosis in diabetic subjects.
Subjects and methods. The study included forty diabetic subjects with NFU (Gr.1), twenty diabetic subjects with PND (Gr.2) and twenty without PND (Gr.3), and ten age and sex matched healthy subjects (Gr.4). Subjects with renal impairment, peripheral arterial disease, ischemic heart disease, smoking or using lipid lowering drugs were excluded. ED was evaluated by measuring the flow mediated dilatation (FMD) of brachial artery using high-resolution ultrasound (Toshiba Power vision 6000 with a 7.5 MHz transducer). Carotid intima media thickness (CIMT) was also used to evaluate atherosclerosis. Fasting blood samples were obtained from all subjects to measure plasma ADMA levels by ELISA kit supplied by EAGLE BIOSCIENCES, INC (Germany).
Results. Gr.1 and Gr.2 were having a significantly lower FMD and higher CIMT in comparison to Gr.3 and Gr.4 (both P< 0.001). However, there was no significant difference between Gr.1 and other study groups as regard plasma ADMA levels (P= 0.126). FMD was inversely and strongly related to CIMT (r= -0.520, P< 0.001). Plasma ADMA was found to be positively correlated with CIMT (r= 0.330, P= 0.003) with no significant correlation with FMD (r = -0.176, P =0.118).
Conclusion. Plasma ADMA levels are not increased in diabetic subjects with NFU, and are not associated with the remarkable ED in these patients. In diabetic subjects, plasma ADMA levels are positively correlated with atherosclerosis.