New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

Feldman, Eva L.; Nave, Klaus Armin; Jensen, Troels Staehelin; Bennett, David L.H.

doi:10.1016/j.neuron.2017.02.005

Cited by 674 publications

(707 citation statements)

References 173 publications

(188 reference statements)

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“…Diabetic neuropathy affects both the peripheral and the autonomic nervous systems, with a variety of concomitant clinical manifestations that are not consistent in occurrence. The pathogenesis of diabetic neuropathy includes chronic hyperglycemia leading to metabolic insults of the nerve structure and diabetic microvascular affection of the vasa nervorum [1]. …”

Section: Introductionmentioning

confidence: 99%

Oropharyngeal Dysphagia and Diabetes Mellitus: Screening of 200 Type 1 and Type 2 Patients in Cairo, Egypt

Zakaria

Bekhet

Khodeir

et al. 2018

Folia Phoniatr Logop

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Background: Although diabetes mellitus is a well-researched systemic endocrinal disease, literature is scarce addressing the co-occurrence of oropharyngeal dysphagia with diabetes. Objective: The aim of this work was to screen Egyptian diabetic patients for symptoms suggestive of oropharyngeal dysphagia using the validated Arabic version of the Eating Assessment Tool (A-EAT-10). Participants and Methods: 200 Egyptian adult diabetic patients, aged from 18 to 59 years participated in the study. The inclusion criteria were being diabetic patients of type 1 or type 2. Patients were asked to complete the A-EAT-10 questionnaire. Results: Age progression and being female were found to be risk factors for dysphagia among diabetic patients participating in this study. The most common symptom among diabetic patients who complained of dysphagia was “I cough when I eat.” Conclusion: The present study suggests the presence of oropharyngeal swallowing problems among patients with diabetes mellitus.

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Section: Introductionmentioning

confidence: 99%

Oropharyngeal Dysphagia and Diabetes Mellitus: Screening of 200 Type 1 and Type 2 Patients in Cairo, Egypt

Zakaria

Bekhet

Khodeir

et al. 2018

Folia Phoniatr Logop

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“…An array of factors, such as dysfunction of mitochondria and endoplasmic reticulum, hypercholesterolemia, endothelial dysfunction, and ischemia/hypoxia, are considered to play an important role in the development of diabetic neuropathy Cashman & Höke, 2015;Feldman, Nave, Jensen, & Bennett, 2017;Gonçalves et al, 2017). Pathological studies of sural nerve biopsies from patients with diabetic neuropathy typically demonstrate axonal atrophy, demyelination, axonal degeneration with regeneration, and microangiopathy (Biessels et al, 2014;Malik et al, 1989Malik et al, , 2005Thomas et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy

et al. 2017

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Objectives: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagyrelated structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Patients and Methods:Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM.Results: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. Conclusions:We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy. K E Y W O R D Sautophagy, diabetes, endoneurial capillary, impaired glucose tolerance, morphometry, peripheral neuropathy

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“…Symptoms include pain, muscle weakness, and sensory loss [37,38]. Diabetic neuropathy affects sensory and autonomic nerve fibers more than motor fibers; this is because the cell body of sensory nerves is located in DRG and the blood nerve barrier (BNB) is leaky in this area allowing toxins to enter and cause damage to the cells [39,40]. In addition, the sensory and autonomic nerve fibers are either unmyelinated or have a thin myelin sheath which makes them more vulnerable [40].…”

Section: Diabetic Neuropathymentioning

confidence: 99%

“…Formation of advanced glycation end products (AGEs) and activation of protein kinase C (PKC) pathway can also contribute to DN. Activation of the PKC pathway causes, for example, vascular changes like basal membrane thickening and endothelial cell proliferation, which lead to hypoxia [32,40,41]. Oxidative stress contributes to development of diabetic neuropathy [44].…”

Section: Diabetic Neuropathymentioning

confidence: 99%

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

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Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy. In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury. Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits. 6 Populärvetenskaplig sammanfattningNervskador (neuropati) orsakade av sjukdomar eller olycksfall påverkar miljontals individer runt om i världen. Nervskador som orsakas av diabetes kallas diabetesneuropati och drabbar varannan patient med diabetes. Neuropati kan också orsakas av kronisk inflammation i nerven eller uppstå utan känd orsak, så kallad kronisk idiopatisk axonal polyneuropati. Patienterna som drabbas av neuropati uppvisar varierande symptom beroende på vilka nerver som drabbas men domningar, stickningar, smärta, känselbortfall och muskelsvaghet finns ofta i symptombilden. Nervskador efter trauma kräver oftast kirurgisk rekonstruktion. För närvarande finns det ingen behandling för diabetesneuropati. Allt fler människor i fysiskt aktiv ålder drabbas av åldersdiabetes (typ 2 diabetes). Detta leder till att fler patienter med diabetes drabbas av traumatiska nervskador som kräver nervreparation. Det är därför viktigt att utveckla reparationsmetoder som fungerar br...

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New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

Cited by 674 publications

References 173 publications

Oropharyngeal Dysphagia and Diabetes Mellitus: Screening of 200 Type 1 and Type 2 Patients in Cairo, Egypt

Oropharyngeal Dysphagia and Diabetes Mellitus: Screening of 200 Type 1 and Type 2 Patients in Cairo, Egypt

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy

Autophagy in Peripheral Neuropathy

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