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Review
. 2024 Jan 9:14:1265372.
doi: 10.3389/fendo.2023.1265372. eCollection 2023.

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Jinxi Zhu  1   2 , Ziyan Hu  1   2 , Yifan Luo  1 , Yinuo Liu  1 , Wei Luo  3 , Xiaohong Du  1 , Zhenzhong Luo  1 , Jialing Hu  4 , Shengliang Peng  1
Affiliations
Review

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Jinxi Zhu et al. Front Endocrinol (Lausanne). .

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.

Keywords: diabetic peripheral neuropathy; diagnosis; molecular mechanisms; signal transduction; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Specific manifestations of axonal myelin sheath injury.
Figure 2
Figure 2
Important Pathways in the Mechanism of DPN.
Figure 3
Figure 3
Patterns of PKC pathway, AGE pathway, insulin pathway, polyol pathway, and hexosamine pathway.
Figure 4
Figure 4
Pattern diagram of other pathways.
Figure 5
Figure 5
Treatment options for chronic pain in DPN. SNRIs, serotonin and norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants.
See this image and copyright information in PMC

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