Levels of soluble advanced glycation end product-receptors and other soluble serum markers as indicators of diabetic neuropathy in the foot

Objective: Advanced glycation end products (AGEs) and the interaction with their receptors (RAGE) play an important role in the pathogenesis of diabetic foot (DF) associated with diabetic neuropathy. Our study examined the association between asymmetric dimethyl arginine (ADMA), fructosamine, nitric oxide (NO), and soluble (s) RAGE levels in serum of diabetic patients with and without neuropathy. Methods: Circulating levels of ADMA, fructosamine, NO, and sRAGE, estimated either chemically or by enzyme-linked immunosorbent assay, were examined in 60 type 2 diabetes mellitus (T2DM) overweight/obese (body mass index, 30.5 ± 1.5 kg/m2) male patients and 20 age-matched (55 T 3 years) obese healthy subjects as control group. The T2DM subjects were categorized as patients without DF (n = 30), and the remaining were patients with DF associated with neuropathy. Results: First sRAGE levels were significantly increased in T2DM patients without DF in comparison to healthy controls (1656.6 [1198.8-2065.4] vs 1111.7 [909-1605.3] pg/mL, respectively; P < 0.05). However, in the DF group (1049.6 [783.7-1221.8] pg/mL), its level decreased significantly in comparison to both groups (P G 0.05). However, ADMA and fructosamine were significantly higher in diabetic patients with DF than both T2DM without DF and healthy controls. Moreover, NO was significantly lower in DF than in diabetic patients without DF and controls (5 T 0.4 and 8 T 0.4 vs 42 T 2.5 Kmol/L, respectively; P G 0.05). Finally, sRAGE levels were significantly correlated with ADMA, fructosamine, and NO. Conclusions: Soluble forms of the receptor for advanced glycation end product could be an endogenous protection factor against occurrence of DF, hence may be of therapeutic value in the treatment of DF. © 2011 by The American Federation for Medical Research.