Magnetic Resonance Neurography Reveals Smoking-Associated Decrease in Sciatic Nerve Structural Integrity in Type 2 Diabetes.

Johann M E Jende,Alexander Juerchott,Felix T Kurz,Sabine Heiland,Stefan Kopf,Martin Bendszus,Peter Nawroth,Christoph Mooshage,Jan B Groener,Zoltan Kender

doi:10.3389/fnins.2021.811085

Abstract

ObjectiveIt is controversially discussed in how far smoking contributes to diabetic polyneuropathy (DPN) in type 2 diabetes (T2D). Diffusion-weighted magnetic resonance neurography (MRN) at 3 Tesla has been shown to provide objective values for structural nerve integrity in patients with T2D. The aim of this study was to investigate the contribution of cigarette smoking on structural nerve integrity in T2D.MethodsThis cross-sectional prospective cohort study investigated the structural integrity of the sciatic nerve in 10 smokers, 40 never-smokers, and 20 ex-smokers with T2D and 10 healthy control subjects, using diffusion tensor imaging MRN at 3 Tesla and semi-automated nerve fiber tracking. Results were correlated with clinical, electrophysiological, and serological data.ResultsThe sciatic nerve’s fractional anisotropy (FA), a parameter for structural nerve integrity, was significantly lower in smokers with T2D when compared to controls (p = 0.002) and never-smokers (p = 0.015), and lower in ex-smokers when compared to controls (p = 0.015). In addition, sciatic nerve radial diffusivity, a marker of myelin damage, was increased in smokers versus controls and never-smokers (p = 0.048, p = 0.049, respectively). Furthermore, FA in T2D patients was negatively correlated with clinical and electrophysiological markers of DPN. FA also showed negative correlations with the pulse wave velocity, a marker of arterial stiffness and associated microangiopathy, in controls (r = −0.70; p = 0.037), never-smokers (r = −0.45; p = 0.004), ex-smokers (r = −0.55; p = 0.009), and a similar trend in smokers (r = −0.63; p = 0.076). Negative correlations were found between FA and skin auto-fluorescence, a marker of tissue advanced glycation end product accumulation and therefore long-term glycemic stress in T2D, in never-smokers (r = −0.39; p = 0.020) and smokers (r = −0.84; p = 0.004), but not in ex-smokers (r = −0.07; p = 0.765).ConclusionThe findings indicate that smoking contributes to sciatic nerve damage in T2D, potentially worsening DPN due to glycemic stress and less microangiopathy-associated myelin damage in active smokers, while angiopathic effects predominate in ex-smokers. To stop smoking may therefore pose a promising preventive measure to slow the progression of DPN in T2D.

Highlights

Distal symmetric diabetic polyneuropathy (DPN) is one of the most disabling complications of diabetes with increasing prevalence affecting about 200 million patients worldwide causing high morbidity and extensive healthcare costs (Alleman et al, 2015)
Several clinical studies concluded that smoking increases the risk for DPN, and it was found recently that smoking is associated with structural changes in dorsal root ganglia (Jende et al, 2020c), it has not yet been possible to quantify the amount and extent of structural nerve damage caused by smoking in vivo
nerve conduction velocities (NCVs) and CMAP, and pulse wave velocity (PWV); (iii) in never-smokers and smokers, fractional anisotropy (FA) was negatively correlated with skin auto fluorescence (SAF), whereas in ex-smokers no such correlation could be found; and (iv) in smokers, radial diffusivity (RD) was positively correlated with High sensitivity Troponin T (hsTNT), SAF, body-mass index (BMI), and hemoglobin A1c (HbA1c) levels

Summary

Introduction

Distal symmetric diabetic polyneuropathy (DPN) is one of the most disabling complications of diabetes with increasing prevalence affecting about 200 million patients worldwide causing high morbidity and extensive healthcare costs (Alleman et al, 2015). Several clinical studies concluded that smoking increases the risk for DPN, and it was found recently that smoking is associated with structural changes in dorsal root ganglia (Jende et al, 2020c), it has not yet been possible to quantify the amount and extent of structural nerve damage caused by smoking in vivo It remains to be determined whether the main contributing factor to nerve damage caused by smoking in T2D is either microangiopathy as a consequence of oxidative stress to the endothelium or oscillations of blood glucose induced by smoking (Csordas and Bernhard, 2013; Christensen et al, 2020)

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