| Objective To investigate the plasma differential metabolites and potential mechanisms of action in patients with type 2 diabetes mellitus and atherosclerosis comorbidity treated with simvastatin. Methods A prospective case-control study was conducted on 30 patients with atherosclerosis comorbidities with type 2 diabetes who were admitted to the Department of Gastroendocrinology, Fuyang Women and Children’s Hospital from November 2022 to June 2023, and 15 patients with atherosclerotic comorbidities of type 2 diabetes who received rosuvastatin treatment were selected as the observation group. According to age, gender, disease course and other indicators 1∶1, 15 patients who refused to use lipid-lowering drugs were matched as the control group. The differences in plasma metabolism between the two groups were analyzed by liquid chromato-mass spectrometry (LC-MS), and multidimensional statistical analysis was performed by unsupervised principal component analysis (PCA) and supervised partial least square analysis (PLS-DA). Differential metabolites were screened with variable importance factor >1, difference factor >1.0 and P＜0.05 as screening conditions, and KEGG pathway enrichment analysis was performed for differential metabolites. Results After 30 days of treatment, compared with the control group, the TC, TG, LDL-C, and HDL-C levels of the observation group were significantly improved (P＜0.05); the difference in the changes in TC, TG, LDL-C, and HDL-C levels between the two groups before and after treatment was statistically significant (P＜0.05). There were 290 different metabolites between the two groups, among which 131 differential metabolites were selected via positive ion mode, with 89 up-regulated and 42 down-regulated metabolites, and 159 differential metabolites were selected via negative ion mode, with 125 up-regulated and 34 down-regulated metabolites. KEGG pathway analysis revealed that seven pathways, including arachidonic acid metabolism, lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, butyric acid metabolism, glycine, serine and threonine metabolism, and tyrosine metabolism, may be potential pathways for the therapeutic effects of rosuvastatin on the comorbidity of type 2 diabetes and atherosclerosis. Among them, arachidonic acid metabolism, lysine degradation, sphingolipid metabolism, and glycerophospholipid metabolism were the most significant pathways (with all P＜0.01). Conclusion Simvastatin can regulate the plasma metabolite levels in patients with type 2 diabetes mellitus and atherosclerosis comorbidity. Its effects may be associated with pathways such as arachidonic acid metabolism, lysine degradation, sphingolipid metabolism, and glycerophospholipid metabolism. |
