Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

09 January 2024 | Jinxi Zhu, Ziyan Hu, Yifan Luo, Yinuo Liu, Wei Luo, Xiaohong Du, Zhenzhong Luo, Jialing Hu and Shengliang Peng
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, characterized by peripheral nerve dysfunction. The most prevalent form is diabetic distal symmetric polyneuropathy (DSPN), which affects 10-15% of newly diagnosed type 2 diabetes (T2DM) patients and can exceed 50% in patients with diabetes for more than 10 years. Common symptoms include bilateral limb pain, numbness, and paresthesia, with severe cases leading to foot ulcers and amputations. The etiology and pathogenesis of DPN are not fully understood, but hyperglycemia, lipid metabolism disorders, and insulin signaling pathway abnormalities are key factors. These factors disrupt the structure and function of the peripheral nervous system, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. Insulin signaling pathway abnormalities inhibit axon repair and promote cell apoptosis. Recent studies have explored various mechanisms contributing to DPN, including oxidative stress pathways, microvascular damage, insulin receptor signaling pathway abnormalities, neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Understanding the contributions of each pathway to neuropathy and their interconnections can help develop more targeted screening and treatment interventions. Key pathways involved in DPN include the protein kinase C (PKC) pathway, polyol pathway, advanced glycation end product (AGE) pathway, hexosamine pathway, and poly(ADP-ribose) polymerase (PARP) pathway. These pathways are activated by hyperglycemia and dyslipidemia, leading to metabolic disorders, oxidative stress, and inflammatory responses. Insulin signaling, which is often impaired in DPN, plays a crucial role in supporting peripheral nerves and promoting axonal growth. Microvascular changes, while controversial, may also contribute to DPN by affecting blood and oxygen supply to nerves, leading to ischemia and hypoxia. Other pathways, such as the Wnt/β-catenin, mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and thyrotropin (TSH) pathways, are also being explored as potential targets for treatment. Diagnosis of DPN involves detailed medical history, sensory tests, and quantitative criteria. Treatment focuses on strict blood sugar control, metabolic syndrome management, and symptom management with medications like anticonvulsants, tricyclic antidepressants, and topical analgesics. While there is no cure for DPN, early intervention can help manage symptoms and prevent progression.Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, characterized by peripheral nerve dysfunction. The most prevalent form is diabetic distal symmetric polyneuropathy (DSPN), which affects 10-15% of newly diagnosed type 2 diabetes (T2DM) patients and can exceed 50% in patients with diabetes for more than 10 years. Common symptoms include bilateral limb pain, numbness, and paresthesia, with severe cases leading to foot ulcers and amputations. The etiology and pathogenesis of DPN are not fully understood, but hyperglycemia, lipid metabolism disorders, and insulin signaling pathway abnormalities are key factors. These factors disrupt the structure and function of the peripheral nervous system, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. Insulin signaling pathway abnormalities inhibit axon repair and promote cell apoptosis. Recent studies have explored various mechanisms contributing to DPN, including oxidative stress pathways, microvascular damage, insulin receptor signaling pathway abnormalities, neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Understanding the contributions of each pathway to neuropathy and their interconnections can help develop more targeted screening and treatment interventions. Key pathways involved in DPN include the protein kinase C (PKC) pathway, polyol pathway, advanced glycation end product (AGE) pathway, hexosamine pathway, and poly(ADP-ribose) polymerase (PARP) pathway. These pathways are activated by hyperglycemia and dyslipidemia, leading to metabolic disorders, oxidative stress, and inflammatory responses. Insulin signaling, which is often impaired in DPN, plays a crucial role in supporting peripheral nerves and promoting axonal growth. Microvascular changes, while controversial, may also contribute to DPN by affecting blood and oxygen supply to nerves, leading to ischemia and hypoxia. Other pathways, such as the Wnt/β-catenin, mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and thyrotropin (TSH) pathways, are also being explored as potential targets for treatment. Diagnosis of DPN involves detailed medical history, sensory tests, and quantitative criteria. Treatment focuses on strict blood sugar control, metabolic syndrome management, and symptom management with medications like anticonvulsants, tricyclic antidepressants, and topical analgesics. While there is no cure for DPN, early intervention can help manage symptoms and prevent progression.
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