Emerging Nonpharmacologic Interventions to Treat Diabetic Peripheral Neuropathy

Enders, Jonathan; Elliott, Daniel S.; Wright, Douglas E.

doi:10.1089/ars.2022.0158

Cited by 4 publications

(1 citation statement)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, subtypes of Charcot-Marie-Tooth disease (CMT) include impaired axonal transport and mitochondrial function [45][46][47][48]. Notably, these consequences are implicated in chemotherapy-induced peripheral neuropathies [49][50][51][52] and neuropathies associated with diabetes and metabolic syndrome [53][54][55][56][57]. Impaired axonal transport is more amenable to the traditional model of Wallerian degeneration, in which disruption of distal nicotinamideadenine dinucleotide (NAD + ) homeostasis and energetic deficiencies lead to SARM1 activation [17,[58][59][60].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Thomas

Enders

Kaiser

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Intraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique. Methods: We conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5). Results: We analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 74 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of -47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of -31.6 % and -34.7% respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents. Interpretation: Reduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Thomas

Enders

Kaiser

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Zhu,

Hu,

Luo

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.

show abstract

Abnormal intraepidermal nerve fiber density in disease: A scoping review

et al. 2023

Self Cite

View full text Add to dashboard Cite

BackgroundIntraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique.MethodsWe conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5).ResultsWe analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 73 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of −47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of −31.6% and −34.7%, respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents.InterpretationReduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

show abstract

Emerging Nonpharmacologic Interventions to Treat Diabetic Peripheral Neuropathy

Cited by 4 publications

References 151 publications

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Abnormal intraepidermal nerve fiber density in disease: A scoping review

Contact Info

Product

Resources

About