Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments

Elafros, Melissa A.; Andersen, Henning; Bennett, David L.H.; Savelieff, Masha G.; Viswanathan, Vijay; Callaghan, Brian C.; Feldman, Eva L.

doi:10.1016/s1474-4422(22)00188-0

Cited by 75 publications

(67 citation statements)

References 110 publications

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“… 273 , 274 Energy and inflammation, oxidative stress, 275 insulin resistance, 276 AGEs, 277 nerve growth factors, 278 activation of the polyol pathway, 279 and activation of the hexosamine and PKC pathways 280 are core pathological factors and processes similar to those of other DM vascular complications. 281 , 282 Glucose and fatty acid metabolism, 283 neural metabolism, 284 and exosome regulation have recently attracted attention. 285 , 286 Much more is known about peripheral neuropathy than about DPVD.…”

Section: Introductionmentioning

confidence: 99%

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Liu

et al. 2023

Sig Transduct Target Ther

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Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.

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Section: Introductionmentioning

confidence: 99%

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Liu

et al. 2023

Sig Transduct Target Ther

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“…Of note, the diabetic vasculature is stimulated by the long-term presence of high glucose concentrations. This leads to atherosclerosis and luminal narrowing, which results in an insufficient blood supply to the distal peripheral circulation, hypoperfusion and intimal ischemia in the nerve trophoblastic vessels, further aggravating nerve degeneration and necrosis [ 76 ].…”

Section: The Pathological Process Of Dusmentioning

confidence: 99%

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Wei

et al. 2023

Biomater Res

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Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

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“…The clinical symptoms of DPN include pain, numbness, insect crawling, fever, and is a risk factor for diabetes foot and even amputation (Yu 2021). Studies have shown that the pathogenesis of DPN is related to a series of impairments such as axonal atrophy, demyelination, loss of nerve ber function and delayed regeneration of peripheral nerves in a hyperglycemic state (Elafros et al 2022). There is mounting evidence that many biological processes, such as cell proliferation, apoptosis, and autophagy, are involved in the pathogenesis of DPN (Jia et al 2018; Zhu et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Identifying Autophagy-Related Genes contributing to Diabetes Peripheral Neuropathy

Xing

Liu

et al. 2023

Preprint

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Purpose Diabetes has a common complication called diabetic peripheral neuropathy (DPN), whose exact pathophysiology is still unknown. In ischemic reperfusion injury to nerve tissues, the treatment of neurodegenerative illnesses, and the repair of nerve tissue injuries, autophagy is crucial. Through bioinformatics analysis and validation, we hope to pinpoint the possible autophagy-related differential expressed genes (DEGs) of DPN. Methods The GEO database provided the mRNA expression profile dataset GSE185011. R software was used to look for possible DPN autophagy-related DEGs. Then, for the autophagy-related DEGs, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out. In the validation set GSE95849, the RNA expression of autophagy-related DEGs was verified in blood samples from DPN patients and healthy controls. Results Between 5 DPN patients and 5 healthy controls, a total of 33 autophagy-related DEGs (5 up-regulated genes and 28 down-regulated genes) were found. The PPI analysis showed interactions between these autophagy-related DEGs. The GO and KEGG enrichment analyses revealed a number of enriched terms including mitophagy and autophagy. The results of the validation set demonstrated that the expression levels of the genes P4HB, GAPDH, CTSB and RAB7A were significantly decreased, ATG5, CASP3, SQSTM1, ULK1, and 9 other genes in DPN patients were significantly up-regulated in the DPN patients, which were compatible with the bioinformatics analysis of mRNA microarray. Conclusion Through bioinformatics research, we identified 17 putative autophagy-related DEGs in DPN. By regulating autophagy, ATG5, CASP3, SQSTM1, ULK1, and another 13 genes may have an impact on DPN formation. These findings might deepen our understanding of DPN and help with DPN treatment.

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Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments

Cited by 75 publications

References 110 publications

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Identifying Autophagy-Related Genes contributing to Diabetes Peripheral Neuropathy

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