129-OR: Increased Triglyceride Levels Are Associated with a Distinct Lipid-Associated Protein Biomarker Profile of Diabetic Foot Ulcers

Background and Aims: The substantial challenges to medical regimens of persons with diabetic foot ulcers (DFU) are associated with clinical heterogeneity and poorly defined risk factors. We examined the proteomic profile of newly detected DFUs to identify at-risk patients and propose a strategy for timely interventions.

Materials and Methods: 112 people with type 1 and 2 diabetes, whose ulcer tissue swaps were collected upon the first observation, were included in an observational study. Enrolled persons were categorised according to healing time: fast healing (FH, <40 days), slow healing (SH, >40 days; <6 months), and chronic non-healing (CH, >6 months). After 6 months of follow-up data were obtained from the electronic patient register. Protein profiles of tissue ulcer swaps were assessed using untargeted proteomics and MaxQuant tools. Proteins with less than 3 valid observations per group were excluded. The analysis included a significance level of 0.05 after FDR correction.

Results: Triglyceride levels of 2.5 mmol/l in CH were markedly elevated compared to FH (1.7, p= 0.013). Out of 223 proteins, 46 were highly correlated to plasma lipid and lipoprotein abnormalities. Gene Ontology (GO) and pathway enrichment from Panther.db show that 28 multiple and overlapping pathways are associated with chylomicrons lipoprotein particle remodelling (>100-fold-enrichment, p<0.0001). Furthermore, the dyslipidaemia pattern in CH compared to FH was characterised by the downregulation of HDL-controlling apolipoproteins family members apoA2, 4 (0.7-fold), upregulation of apoC1-3 involved in triglyceride-rich lipoproteins (1.4-fold), as well as the principal cholesterol carrier Apo-E (1.4-fold).

Conclusions: Our findings show consistent wound tissue lipoprotein profile alterations corresponding to a chronic wound phenotype. We plan to validate these findings using multiomics approaches, before integrating them into routine clinical practice.