engleski

Advanced Glycation Endproducts in Peripheral Nerve in Type 2 Diabetes with Neuropathy

Advanced glycation endproducts accumulate over proteins as a consequence of diabetic hyperglycemia, and thus contribute to the pathogenesis of diabetic complications. To improve the understanding of the pathology of diabetic neuropathy, AGE accumulation was analyzed in sural and/or femoral nerves obtained under spinal anesthesia from type 2 diabetic patients (n=8) with both distal symmetrical polyneuropathy and proximal neuropathy. Pronounced AGE immunoreactivity was detected on axons and myelin sheaths in 90% of diabetic peripheral nerves but not in the control specimen. The intensity of axonal AGE immunopositivity significantly correlated with the severity of morphological alterations (p<0.005). These structural changes of axons may have been related to neurophyisiological abnormalities in study patients, including significant retardation of the motor and sensory conductivity with very low amplitudes of muscular and neural responses. AGE localization, demonstrated by immunohistochemical methods, was also present in the endoneurium, perineurium and microvessels. Morphometric analysis of the diabetic peripheral nerve showed perineurial thickening (DM vs C: 15.5&#61617; 4.9 vs 6.6&#61617; 2.1 &#61549; m, p<0.001), narrowing of the microvessel lumina (DM vs C: 66.6&#61617; 50.5 vs 579.5&#61617; 38.4 x103 &#61549; m2, p<0.000) and significant reduction in the number of preserved axons (DM vs C: 3.6&#61617; 3 vs 8.9&#61617; 2.3 per area of 105 &#61549; m2, p<0.037). In the present study, the sera of diabetic patients were shown to contain autoantibodies to epitope(s) of AGE structure. Additionally, the presence of soluble immune complexes containing AGE moiety was demonstrated. In conclusion, these results provide evidence for excessive AGE formation on peripheral nerve components, primarily on axons, and a significantly higher level of circulating AGE-immune complexes in patients with both distal diabetic polyneuropathy and proximal neuropathy.

Advanced glycation; Peripheral nerve; Neurophaty

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