Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease.

Methods: The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes.

Results: In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes.

Conclusion: Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets.

Trial registration: The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).

Keywords: Arachidonic acid; Atherosclerosis; Carotid; Diabetes; Inflammation.

Fig. 1

A: Violin plot of C-reactive protein (CRP) levels in control and T2DM patients. B: Violin plot of IL-1β levels in control and T2DM patients. C: Correlation between plasma HsCRP levels and triglycerides (R and P values were obtained by the Spearman rank test)

Fig. 2

A: Forest plots showing odds ratio values and 95% confidence intervals for multivariable logistic regression analysis of diabetes and biological variables. B: Receiver operating characteristic curve (ROC) for the prediction of type 2 diabetes based on the selected biological parameters. (AUC: Area under the Curve)

Fig. 3

A: Correlation matrix of 2-AA-LPC with systemic and carotid plaque biomarkers. Correlations were determined by Spearman’s rank correlation. Intersections between lines and columns indicate the Spearman’s rank correlation coefficient (ρ) between the two parameters. Spearman ρ value is visualized by blue or red intensities. B: Correlation between relative levels of 2-AA-LPC and 25-hydroxycholesterol levels in carotid plaques (R and P values) were obtained by the Spearman rank test