Kuo Hung-Chou, Lin Chia-Ni, Tsai Sung-Sheng, Chen Chiung-Mei, Lyu Rong-Kuo, Chu Chun-Che, Ro Long-Sun, Liao Ming-Feng, Chang Hong-Shiu, Weng Yi-Ching, Hwang Jawl-Shan
Department of Neurology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
J Diabetes Investig. 2025 Feb;16(2):246-256. doi: 10.1111/jdi.14355. Epub 2024 Nov 16.
This study aimed to identify metabolic markers for diabetic peripheral neuropathic pain (DPNP) in patients with type 2 diabetes mellitus (T2DM).
Blood metabolite levels in the amino acid, biogenic amine, sphingomyelin, phosphatidylcholine (PC), carnitines, and hexose classes were analyzed in nondiabetic control (n = 27), T2DM without DPNP (n = 58), and T2DM with DPNP (n = 29) using liquid chromatography tandem mass spectrometry. Variable importance projection (VIP) evaluation by partial least squares discriminant analysis was performed on clinical parameters and metabolites.
Sixteen variables with VIP > 1.0 (P < 0.05) were identified across all patient groups, and 5 variables were identified to discriminate between the two T2DM groups. DPNP patients showed elevated fasting blood glucose, glutamate, PC aa C36:1, lysoPC a C18:1, and lysoPC a C18:2, while low-density lipoprotein cholesterol, phenylalanine, and tryptophan were reduced. Glutamate, lysoPC a C18:1, and lysoPC a C18:2 discriminated T2DM with DPNP from those without DPNP with an AUC of 0.671. The AUC was improved to 0.765 when ratios of metabolite pairs were considered.
Blood metabolites include glutamate, and phospholipid-related metabolites implicated in neuropathic pain may have the potential as biomarkers for DPNP. Further investigation is required to understand the mechanism of action of these altered metabolites in DPNP.
本研究旨在确定2型糖尿病(T2DM)患者糖尿病性周围神经病理性疼痛(DPNP)的代谢标志物。
使用液相色谱串联质谱法分析非糖尿病对照组(n = 27)、无DPNP的T2DM患者(n = 58)和有DPNP的T2DM患者(n = 29)的氨基酸、生物胺、鞘磷脂、磷脂酰胆碱(PC)、肉碱和己糖类别的血液代谢物水平。通过偏最小二乘判别分析对临床参数和代谢物进行变量重要性投影(VIP)评估。
在所有患者组中鉴定出16个VIP>1.0(P<0.05)的变量,鉴定出5个变量以区分两个T2DM组。DPNP患者空腹血糖、谷氨酸、PC aa C36:1、溶血PC a C18:1和溶血PC a C18:2升高,而低密度脂蛋白胆固醇、苯丙氨酸和色氨酸降低。谷氨酸、溶血PC a C18:1和溶血PC a C18:2区分有DPNP的T2DM与无DPNP的T2DM,曲线下面积(AUC)为0.671。当考虑代谢物对的比率时,AUC提高到0.765。
血液代谢物包括谷氨酸,与神经病理性疼痛相关的磷脂代谢物可能有潜力作为DPNP的生物标志物。需要进一步研究以了解这些改变的代谢物在DPNP中的作用机制。