Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer

Abstract

Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.

Keywords: Diabetic foot ulcer; mass spectrometry; metabolomic analysis; phospholipids; type 2 diabetes mellitus.

Figure 1.

Partial Least Square-Discriminant Analysis (PLS-DA) of the serum non-targeted metabolomic profile of the study participants. Blue: no T2DM or control group; orange: DFU G0 group; gray: DFU G1 group; green: DFU G2 group; purple: DFU G3 group. Abbreviations: DFU, diabetic foot ulcer; TD2M, type-2 diabetes mellitus.

Figure 2.

Unsupervised hierarchical clustering of the top 10 features that discriminate the study groups obtained from the PLS-DA model. Abbreviation: PLS-DA, partial least square-discriminant analysis.

Figure 3.

Box-plots of the major discriminant metabolites obtained from the PLS-DA. Abbreviations: DFU, diabetic foot ulcer; PLS-DA, Partial Least Squares-Discriminant Analysis; T2DM, type-2 diabetes mellitus. *Indicate significant (p<0.05) differences between groups.