The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy.

Elisabetta Toffanin,Marcello Romano,Susanna Ruggero,Matteo Francesco Lauriola,Giampietro Zanette,Marialuigia Praitano,Chiara Briani,George Chummar Peter,Francesca Magrinelli,Giuseppa Triolo,Stefano Tamburin

doi:10.1155/2015/547834

Abstract

Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.

Highlights

Diabetic peripheral neuropathy (DPN) is the most common long-term complication of type 2 diabetes mellitus (DM) and affects approximately half of the patients over the course of disease [1]
IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or neuropathic pain (NP)
body mass index (BMI) was significantly smaller in IL-10+ patients (25.2 ± 3.2 kg/m2) in comparison to the IL-10− group (30.5 ± 5.5 kg/m2; Mann-Whitney U test: p = 0.02; Table 1)

Summary

Introduction

Diabetic peripheral neuropathy (DPN) is the most common long-term complication of type 2 diabetes mellitus (DM) and affects approximately half of the patients over the course of disease [1]. Small and large peripheral nerve fibers may be involved in DPN. Large nerve fiber damage causes paresthesia, sensory loss, and muscle weakness and small nerve fiber damage is associated with pain, anesthesia, foot ulcer, and autonomic symptoms. Nerve conduction study (NCS) is important in experimental studies in that it may document the extent and severity of nerve involvement and demonstrates the presence of axonal damage and/or demyelination. The mechanisms of DPN are only partially understood, and hyperglycemia, dyslipidemia, and insulin resistance are considered to be involved in its pathophysiology. The observation that successful treatment of hyperglycemia often fails to prevent DPN suggests the presence of early biochemical mediators that, once activated, may act independently of the initial stimulus. The biochemical pathways leading to nerve damage in DPN are complex and they include the accumulation of sorbitol, lipoxygenase activation, oxidization, and glycation of proteins and lipoproteins. Glucose and oxidized and glycated proteins may bind various receptors on neurons

Methods

Results

Conclusion