Plasma ceramides as biomarkers for microvascular disease and clinical outcomes in diabetes and myocardial infarction

Abstract

Background: Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease.

Methods: This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used.

Results: Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p < 0.001).

Conclusions: Plasma ceramides serve as potential predictors for health status and microvascular disease phenotypes in diabetic patients.

Keywords: And myocardial infarction; Ceramides; Diabetic; Microvascular disease.

Fig. 1

Study workflow

Fig. 2

Heat map with longitudinal ceramide kinetic analysis (Group 3/N = 48 pts). *P -value = 0.664

Fig. 3

Differences between plasma ceramide concentrations

Fig. 4

Entire cohort: main outcomes

Fig. 5

Roc curve analyses of three reference ceramide ratios (C 18.0/16.0; C 18.0/24.0 & C 18.0/24.1) Versus 11-ceramide panel

Fig. 6

Visual conclusion of the study with the progression from non-diabetes to diabetes with microcirculatory disease and the signature patterns of biomarkers with significant statistical association