Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania.
Department of Pediatrics 1, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania.
Int J Mol Sci. 2024 Sep 27;25(19):10395. doi: 10.3390/ijms251910395.
There is an increasing prevalence of diabetes mellitus (DM), particularly type 2 DM (T2DM), and its associated complications. T2DM is linked to insulin resistance, chronic inflammation, and oxidative stress, which can lead to both macrovascular and microvascular complications, including peripheral diabetic neuropathy (PDN). Inflammatory processes play a key role in the development and progression of T2DM and its complications, with specific markers like C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor (TNF)-α being associated with increased risk. Other key inflammatory markers such as nuclear factor kappa B (NF-κB) are activated under hyperglycemic and oxidative stress conditions and contribute to the aggravation of PDN by regulating inflammatory gene expression and enhancing endothelial dysfunction. Other important roles in the inflammatory processes are played by Toll-like receptors (TLRs), caveolin 1 (CAV1), and monocyte chemoattractant protein 1 (MCP1). There is a relationship between vitamin D deficiency and PDN, highlighting the critical role of vitamin D in regulating inflammation and immune responses. The involvement of macrophages in PDN is also suspected, emphasizing their role in chronic inflammation and nerve damage in diabetic patients. Vitamin D supplementation has been found to reduce neuropathy severity, decrease inflammatory markers, and improve glycemic control. These findings suggest that addressing vitamin D deficiency could offer therapeutic benefits for PDN. These molecular pathways are critical in understanding the pathogenesis of DM complications and may offer potential biomarkers or therapeutic targets including anti-inflammatory treatments, vitamin D supplementation, macrophage phenotype modulation, and lifestyle modifications, aimed at reducing inflammation and preventing PDN. Ongoing and more extensive clinical trials with the aim of investigating anti-inflammatory agents, TNF-α inhibitors, and antioxidants are needed to advance deeper into the understanding and treatment of painful diabetic neuropathy.
糖尿病（DM），尤其是 2 型糖尿病（T2DM）及其相关并发症的患病率正在不断上升。T2DM 与胰岛素抵抗、慢性炎症和氧化应激有关，这可能导致大血管和微血管并发症，包括周围性糖尿病神经病变（PDN）。炎症过程在 T2DM 及其并发症的发生和发展中起着关键作用，特定标志物如 C 反应蛋白（CRP）、白细胞介素（ILs）和肿瘤坏死因子（TNF）-α与风险增加相关。其他关键炎症标志物，如核因子 kappa B（NF-κB），在高血糖和氧化应激条件下被激活，并通过调节炎症基因表达和增强内皮功能障碍，加剧 PDN。Toll 样受体（TLRs）、小窝蛋白 1（CAV1）和单核细胞趋化蛋白 1（MCP1）在炎症过程中也起着重要作用。维生素 D 缺乏与 PDN 之间存在关系，突出了维生素 D 在调节炎症和免疫反应中的关键作用。巨噬细胞在 PDN 中的参与也受到怀疑，强调了它们在糖尿病患者慢性炎症和神经损伤中的作用。维生素 D 补充已被发现可减轻神经病变严重程度、降低炎症标志物并改善血糖控制。这些发现表明，解决维生素 D 缺乏可能为 PDN 提供治疗益处。这些分子途径对于理解 DM 并发症的发病机制至关重要，并可能提供潜在的生物标志物或治疗靶点，包括抗炎治疗、维生素 D 补充、巨噬细胞表型调节和生活方式改变，旨在减少炎症并预防 PDN。需要进行更多的临床试验，以研究抗炎剂、TNF-α 抑制剂和抗氧化剂，以深入了解和治疗痛性糖尿病神经病变。
