Molecules (Apr 2022)

High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients

  • Anca Suteanu-Simulescu,
  • Alina Diana Zamfir,
  • Raluca Ica,
  • Mirela Sarbu,
  • Cristian V. A. Munteanu,
  • Florica Gadalean,
  • Adrian Vlad,
  • Flaviu Bob,
  • Dragos Catalin Jianu,
  • Ligia Petrica

DOI
https://doi.org/10.3390/molecules27092679
Journal volume & issue
Vol. 27, no. 9
p. 2679

Abstract

Read online

Considering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (HR) mass spectrometry (MS) and tandem MS (MS/MS) for the determination of gangliosides in the urine of DKD patients. This study was focused on: (i) testing of the HR MS and MS/MS feasibility and performances in mapping and sequencing of renal gangliosides in Type 2 DM patients; (ii) determination of the changes in the urine gangliosidome of DKD patients in different stages of the disease—normo-, micro-, and macroalbuminuria—in a comparative assay with healthy controls. Due to the high resolution and mass accuracy, the comparative MS screening revealed that the sialylation status of the ganglioside components; their modification by O-acetyl, CH3COO−, O-fucosyl, and O-GalNAc; as well as the composition of the ceramide represent possible markers for early DKD detection, the assessment of disease progression, and follow-up treatment. Moreover, structural investigation by MS/MS demonstrated that GQ1d(d18:1/18:0), GT1α(d18:1/18:0) and GT1b(d18:1/18:0) isomers are associated with macroalbuminuria, meriting further investigation in relation to their role in DKD.

Keywords