Improvement of temperature and flow in feet of subjects with diabetes with use of a transdermal preparation of L-arginine: a pilot study.

Circulatory impairment and its sequlae have long been known to be major complications of diabetes. It has been shown that in diabetes, the functionality of the endothelial nitric oxide (NO)/nitric oxide synthase (eNOS) system is impaired (1–3). NO is generated in the endothelium through the oxidation of the amino acid l-arginine by the enzyme eNOS. NO causes vascular smooth muscle to relax, resulting in increased blood flow. In addition to being a substrate of eNOS, l-arginine facilitates the dimerization of two identical subunits, forming a homodimer. The enzyme is only active in the dimeric form. Under proper conditions, dimerization occurs rapidly, on a timescale of minutes. Once formed, the dimer is stable (4). Subjects with diabetes have abnormally low levels of l-arginine (5) and elevated levels of the eNOS inhibitor asymmetric dimethylarginine (ADME) (6) in their plasma. Though the value of increasing l-arginine levels in cases of impaired circulation is …