Sphingolipid metabolism plays a key role in diabetic peripheral neuropathy

Abstract

Introduction: As the most common chronic complication of diabetes mellitus (DM), diabetic peripheral neuropathy (DPN) seriously affects the quality of life of DM patients. So, it is of great significance for the diagnosis and treatment of DPN. In recent years, there have been numerous studies on pathogenesis and biomarkers of DM, but there are few studies on the biomarkers of DPN.

Objectives: This research is intended to identify abnormal metabolic pathways, search for potential biomarkers of DPN, and provide a metabolic basis for the diagnosis and mechanism of DPN.

Methods: Serum samples from 23 healthy controls (HC), 42 DM patients and 30 DPN patients and urine samples from 42 HC, 40 DM patients, and 30 DPN patients were collected. UPLC-Q-TOF/MS was used to analyze the samples. Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least squares discriminant analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). The biomarkers were then enriched and pathway analyzed.

Results: 12 potential DPN biomarkers were identified from patient's serum. 11 potential DPN biomarkers were identified from the patient's urine. Among them, the diagnostic ability of gluconic acid, lipoic acid, sphinganine, bilirubin, sphingosine and 4-hydroxybenzoic acid was increased by ROC analysis. Potential biomarkers suggest that the disorder of DPN metabolism may be linked to sphingolipid metabolism.

Conclusions: This research laid a theoretical foundation for the diagnosis and pathogenesis of DPN.

Keywords: Biomarkers; Diabetic peripheral neuropathy; Metabolomics; Sphingolipid metabolism.