School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia.
Department of Neurology, Prince of Wales Hospital, Sydney, NSW, Australia.
Diabetologia. 2024 Mar;67(3):561-566. doi: 10.1007/s00125-023-06072-6. Epub 2024 Jan 8.
AIMS/HYPOTHESIS: Diabetic peripheral neuropathy (DPN) is a highly prevalent cause of physical disability. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes and animal studies have shown that glucagon-like peptide-1 (GLP-1) receptors are present in the central and peripheral nervous systems. This study investigated whether GLP-1 RAs can improve nerve structure.
Nerve structure was assessed using peripheral nerve ultrasonography and measurement of tibial nerve cross-sectional area, in conjunction with validated neuropathy symptom scores and nerve conduction studies. A total of 22 consecutively recruited participants with type 2 diabetes were assessed before and 1 month after commencing GLP-1 RA therapy (semaglutide or dulaglutide).
There was a pathological increase in nerve size before treatment in 81.8% of the cohort (n=22). At 1 month of follow-up, there was an improvement in nerve size in 86% of participants (p<0.05), with 32% returning to normal nerve morphology. A 3 month follow-up study (n=14) demonstrated further improvement in nerve size in 93% of participants, accompanied by reduced severity of neuropathy (p<0.05) and improved sural sensory nerve conduction amplitude (p<0.05).
CONCLUSIONS/INTERPRETATION: This study demonstrates the efficacy of GLP-1 RAs in improving neuropathy outcomes, evidenced by improvements in mainly structural and morphological measures and supported by electrophysiological and clinical endpoints. Future studies, incorporating quantitative sensory testing and measurement of intraepidermal nerve fibre density, are needed to investigate the benefits for small fibre function and structure.
目的/假设：糖尿病周围神经病变（DPN）是导致身体残疾的一个主要原因。胰高血糖素样肽-1 受体激动剂（GLP-1 RAs）被用于治疗 2 型糖尿病，动物研究表明，胰高血糖素样肽-1（GLP-1）受体存在于中枢和外周神经系统中。本研究旨在探讨 GLP-1 RAs 是否能改善神经结构。
使用外周神经超声检查和测量胫神经横截面积来评估神经结构，并结合有效的神经病变症状评分和神经传导研究。总共评估了 22 名连续招募的 2 型糖尿病患者，在开始 GLP-1 RA 治疗（司美格鲁肽或度拉糖肽）前和治疗后 1 个月进行评估。
在治疗前，81.8%的患者（n=22）存在神经大小的病理性增大。在 1 个月的随访中，86%的患者的神经大小得到改善（p<0.05），其中 32%恢复到正常神经形态。在 3 个月的随访研究（n=14）中，93%的患者的神经大小进一步改善，同时神经病变的严重程度降低（p<0.05），以及腓肠感觉神经传导幅度改善（p<0.05）。
结论/解释：本研究表明 GLP-1 RAs 能有效改善神经病变的结果，主要表现在结构和形态指标的改善，并得到了电生理和临床终点的支持。未来的研究需要纳入定量感觉测试和表皮内神经纤维密度的测量，以研究其对小纤维功能和结构的益处。
