Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Abstract

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.

Development of ovalbumin implants with different spatial configurations for treatment of peripheral nerve injury

“…The growth of neural axons is affected by various regulatory factors and extracellular matrix in scar tissue and granulation tissue. For example, during tissue healing, cell growth factors secreted by the relevant cells, such as vascular endothelial growth factor (VEGF), transforming growth factor-1 (TGF-1), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs) can promote cell growth and differentiation, which have a significant role in wound healing [ 58 ]. In this study, immunohistochemical analysis was performed on the subcutaneous injury site, and the fluorescence intensity of nerve fibers in the E10/70% and 20 kV 25 μL/min groups was lower than that of normal tissues at the one-week time point, indicating that the amount of nerve fiber growth promoted by the membrane in the E10/70% group and the fiber scaffolds in the 20 kV 25 μL/min group failed to reach the level of normal tissues in a short period of time.…”

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

“…Diabetic peripheral neuropathy (DPN) ( Bodman and Varacallo, 2023 ; Zhu et al., 2024 ) is a type of diabetic neuropathy that mainly affects the distal lower extremities and is often characterized by sensory loss, numbness, pain, gait disturbances, and amputation. A study on the characteristics of the gut microbiota in DPN showed that the abundance of Actinomycetes and Firmicutes is increased in DPN, whereas that of Bacteroides is decreased.…”