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.

Lipidomics Characterization of the Microbiome in People with Diabetic Foot Infection Using MALDI-TOF MS

“…Furthermore, some lipids may stick to the precipitated proteins present in the form of the white ring at the interface between the aqueous and the organic phase during lipids extraction via the Folch method and therefore may be lost since only the organic layer is used for further analysis. Matrix selection also matters since for example DHB, which is the most commonly used matrix in lipid analysis, tends to ionize phospholipids with quaternary ammonia groups such as lyso(monoacyl)-phosphatidylcholine or sphingomyelin, whereas negatively charged phosphatidylinositol and phosphatidylserine are detected with very low sensitivity when the positive ion detection mode is used . All together this may explain the differences in the lipidomic profiles of the Gram-positive and -negative species revealed in our and cited works and emphasize the need for looking for optimal and standardized lipid extractions and analysis protocols to facilitate interlaboratory trials comparison.…”

“…For this purpose, lipid fingerprints obtained from lipidomic analysis of lipid extracts, utilizing matrix-assisted laser desorption/ionization (MALDI) techniques and advanced chemometric techniques, were compared. It should be emphasized that there are existing studies in the scientific literature concerning lipidomic analysis conducted in individuals with diabetic foot ulcers. , Additionally, a comparison of the lipid profiles of Gram-positive and Gram-negative bacteria was performed. The information obtained from these studies will be extremely valuable for future research endeavors focused on the construction of microbial lipid libraries for identification purposes.…”

Multiomics Analysis Unravels Alteration in Molecule and Pathways Involved in Nondiabetic Chronic Wounds

“…Altered cell function and mobility result in neovascularization and tissue development. Moreover, keratinocyte and fibroblast migration and proliferation are inhibited, while apoptosis is enhanced, leading to epidermal formation abnormalities. − …”

“…Moreover, keratinocyte and fibroblast migration and proliferation are inhibited, while apoptosis is enhanced, leading to epidermal formation abnormalities. 4 − 11 …”