Evaluation of Urine Exosome Lecithin Cholesterol Acyltransferase as a Biomarker for Diabetes Diagnosis and Dyslipidemia

AIMS: Given the necessity for diabetes monitoring, investigating the expression of lipid metabolism-related proteins may provide valuable insights for disease surveillance and mechanistic elucidation. MATERIALS AND METHODS: LC-MS/MS was used to analyse the expression of lipid metabolism-related proteins in urine exosomes. Biomarkers were screened and their clinical significance was evaluated. Insulin-resistant hepatocytes and diabetic mouse models were established to validate and explore the underlying mechanisms. RESULTS: Logistic regression analysis revealed that elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) were independent risk factors for diabetes. In normal controls and those with prediabetes, females had higher total cholesterol (TC) and HDL-C but lower TG compared to males, whereas no gender differences were observed in the diabetic group. 29 lipid metabolism-related proteins were screened by proteomics, among which lecithin cholesterol acyltransferase (LCAT) was the target protein. Disordered lipid metabolism and upregulation of LCAT were observed in diabetic patients, insulin-resistant cells, and diabetic mice. The liver may be a key organ of early diabetic injury, as evidenced by disorganised hepatocyte arrangement and compensatory LCAT production during the prediabetic stage. As the disease progresses to diabetes, hepatic steatosis significantly worsens, accompanied by elevation of serum and urine LCAT. Urine exosome LCAT not only holds diagnostic value but also exhibits distinctive dynamic changes: an early rise in diabetes followed by a decline during periods of poor glycaemic control (HbA1c ≥ 8% or FBG > 7.8 mmol/L). CONCLUSIONS: LCAT, a critical regulator of lipid metabolism, could serve as a novel biomarker for detection and monitoring of diabetes.