Abstract

DIABETIC POLYNEUROPATHY: ROLE OF OXIDATIVE STRESS AND INFLAMMATION

Qasim H. Abdullah, Sherwan H. Omer* and Mohammed O.Mohammed

ABSTRACT

Background: The pathogenesis of diabetic peripheral polyneuropathy occurs as a consequence of complex interactions among multiple hyperglycemia initiated mechanisms, impaired insulin signaling, inflammation and disturbances of metabolism. Increasing evidence has highlighted the roles of oxidative stress and inflammation in the promotion of diabetic complication including diabetic polyneuropathy. Objective: To evaluate the role of oxidative stress and inflammation in the pathogenesis of peripheral polyneuropathy in patients with type 2 diabetes mellitus. Subjects and Methods: This cross-sectional study involved 50 healthy control subjects and 103 patients with type 2 diabetes mellitus. The entire subjects met certain inclusion and exclusion criteria to exclude other possible contributing factors of neuropathy. According to the results of nerve conduction study, diabetic patients were divided into three groups including diabetic patients with normal nerve conduction study, diabetic with polyneuropathy and diabetic patients with entrapment neuropathy. The following biochemical parameters were measured: Serum total antioxidant capacity (TAC) by ELISA technique, serum soluble receptors for advanced glycation end products (sRAGE) by ELISA technique, serum gamma glutamyl transferase, serum high sensitivity C-reactive protein by fluorescence immunoassay technique. Results: Type 2 diabetic patients with or without neuropathy showed significantly lower serum TAC levels compared to control group, Mean serum RAGE level was lower among diabetic patients with polyneuropathy compared to diabetic with entrapment neuropathy (249.7 Vs 312.5 pg/ml, P = 0.001) and diabetic with normal nerve conduction study (249.7 Vs 308.8 pg/ml, P =0.001). Patients with peripheral polyneuropathy showed significantly higher serum levels of hs-CRP and GGT compared with other diabetic groups as well as control subjects. In diabetic patients with polyneuropathy, serum hs-CRP is significantly inversely correlated with sensory nerve action potential amplitude of median, ulnar, radial and sural nerves. Serum hs-CRP significantly positively correlated with serum GGT (r = 0.592, P < 0.001), while serum GGT is significantly positively correlated with sural sensory latency (r = 356, P = 0.009) and negatively correlated with median sensory nerve action potential amplitude ( r = -0.315, P = 0.021). Conclusions: Data of the present study demonstrated that inflammation and oxidative stress play essential role in the pathophysiology of peripheral polyneuropathy in patients with type 2 diabetes mellitus.

Keywords: diabetes mellitus, polyneuropathy, oxidative stress, inflammation.