时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, the clinical efficacy of aldose reductase inhibitors in improving neurological function is limited [, ], and the spatiotemporal distribution of PKC activation and AGEs accumulation cannot fully explain phenomena such as the distal-priority involvement in DN, subtype differences, and progression despite glycaemic control [–].；Consequently, this article focuses on mitochondrial dysfunction as a key mechanism, examining its role in DN-related nerve damage, its interactions with other pathological factors, the strength of evidence across different DN subtypes, and the challenges associated with mitochondrial-targeted interventions and translation.
方法
Hyperglycaemia, lipotoxicity, and microvascular stress converge on core mitochondrial injury-ATP deficiency, excessive ROS generation, and Ca²⁺ dyshomeostasis-followed by failure of mitochondrial dynamics, axonal transport, mitophagy, and ER-mitochondrial communication.；Single-point detection of microtubule-associated protein 1 light chain 3 (LC3-II), p62, PINK1 or Parkin cannot distinguish between changes in flux and degradation blockage; a comprehensive assessment combining mt-Keima, mito-QC, lysosomal inhibition assays and mitochondrial respiration measurements is required [, , ].；However, whether painful DPN, CAN, gastrointestinal autonomic symptoms and cognitive decline constitute a stable clinical clustering phenotype remains to be verified through prospective cohort studies [–].
核心结论
Diabetic neuropathy (DN) is one of the most common and debilitating complications of diabetes; approximately half of all people with diabetes will experience some degree of nerve damage during the course of their illness, with the risk of developing the condition increasing as the duration of the disease lengthens [–].；DN significantly increases the risk of adverse outcomes such as pain, falls, diabetic foot ulcers, anxiety, depression and muscle weakness, and leads to higher rates of emergency department visits and hospital admissions, severely impacting quality of life [–].；Autonomic neuropathy may also precede the onset of obvious symptoms and significantly increase cardiovascular and gastrointestinal risks [–]. ‖ 结论：It is recommended that a continuous chain of evidence be established in the future, comprising ‘mechanism stratification-measurable endpoints-safe delivery-human validation’; only when candidate interventions can establish consistent evidence linking target regulation, mitochondrial function, small fibre structure and clinical functional benefits will mitochondrial therapy be able to enter the research phase for disease-modifying treatments for DN.
局限
This perspective helps to explain why neuropathy can continue to progress even after blood glucose levels have been brought under control, as well as the heterogeneity observed between painful DPN, painless small-fibre loss and autonomic involvement.；The second challenge is patient heterogeneity: the progression of DPN is influenced by factors such as type of diabetes, disease duration, obesity, dyslipidaemia, nephropathy and pain phenotype.；Given the broad physiological roles of these targets, future research must focus on dose-response relationships, tissue exposure, cell-specific delivery and long-term safety in neurons, glial cells and immune cells, whilst avoiding large-scale, non-selec
对本项目的价值
★☆☆☆☆ 线粒体端点既是机制解释层，也是最容易拿到体外 / 影像读数的中间层。
全文来源
PMC JATS 全文（正文 74,201 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Mitochondrial dysfunction in diabetic neuropathy: a core pathogenic hub and therapeutic implications.
- 期刊与标识：J Transl Med · PMID 42947140 · DOI 10.1186/s12967-026-09015-y
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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