Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus

Objective: 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).

Methods: 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.

Results: 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 (p < 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.

Conclusion: 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.