Luo Tao, Jiang Xiao, Xu Ning, Zhao Xinyu, Xie Xingjie, Xia Xiuwen, Bian XiaoLong, Liu Haixia
Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Endocrinology Department, The Second Hospital of Chao Yang, Chaoyang, China.
Front Mol Biosci. 2024 Apr 18;11:1341290. doi: 10.3389/fmolb.2024.1341290. eCollection 2024.
This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers. Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group ( < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency. This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.
本研究旨在探讨2型糖尿病轻度认知障碍（T2DM-MCI）的危险因素、代谢特征及潜在生物标志物，为2型糖尿病（T2DM）患者轻度认知障碍（MCI）的诊断、预防及治疗提供潜在依据。从大连医科大学附属第二医院内分泌科招募了103例T2DM患者纳入本研究。采用蒙特利尔认知评估量表（MoCA）评估所有患者的认知功能。其中，50例患者被归入T2DM-MCI组（MoCA评分<26分），而53例受试者被归入无认知障碍的T2DM（T2DM-NCI）组（MoCA评分≥26分）。采集受试者的血清样本，通过超高效液相色谱-质谱联用仪（UHPLC-MS）生成代谢组学分析数据。对这些组进行分析，以研究小分子代谢物表达、代谢途径及潜在特异性生物标志物的差异。T2DM-MCI组与T2DM-NCI组比较，在受教育年限、胰岛素应用史、胰岛素抵抗指数、胰岛素样生长因子结合蛋白-3（IGFBP-3）及肌酐水平方面存在显著差异。对这些变量进一步进行二元逻辑回归分析表明，低教育水平及低血清IGFBP-3是T2DM-MCI的独立危险因素。代谢组学分析显示，T2DM-MCI组与T2DM-NCI组之间有10种代谢物差异表达（<0.05且FDR<0.05，VIP>1.5）。京都基因与基因组百科全书（KEGG）富集通路分析显示，脂肪酸降解是最显著的通路。受试者工作特征（ROC）分析表明，溶血磷脂酰胆碱（LPC）18:0具有更高的诊断效能。本研究表明，受教育时间较短及血清IGFBP-3水平较低是T2DM-MCI的独立危险因素。发现T2DM-MCI组和T2DM-NCI组的血清代谢物均有改变。LPC 18:0可区分有或无MCI的T2DM患者。脂质代谢异常在T2DM患者MCI的发生发展中起重要作用。
