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

Clinical Diabetes and Endocrinology Pub Date : 2024-09-17 DOI:10.1186/s40842-024-00186-5

Debora Leonor Junqueira, Alexandre Biasi Cavalcanti, Juliana Maria Ferraz Sallum, Erika Yasaki, Isabella de Andrade Jesuíno, Alline Stach, Karina Negrelli, Leila de Oliveira Silva, Marcela Almeida Lopes, Adriano Caixeta, Mark Yy Chan, Jianhong Ching, Valdemir Malechco Carvalho, Andrea Tedesco Faccio, Jeane Tsutsui, Edgar Rizzatti, Rafael Almeida Fonseca, Scott Summers, Henrique Almeida Fonseca, Carlos Eduardo Rochitte, José Eduardo Krieger, Leonardo Pinto de Carvalho

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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.

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血浆神经酰胺作为糖尿病和心肌梗死微血管疾病和临床结果的生物标志物。

背景：神经酰胺最近被确定为与糖尿病（DM）和主要不良心脑血管事件（MACCE）相关的新型生物标志物。本研究旨在探索神经酰胺在诊断微血管疾病中的作用：该研究前瞻性地招募了2018年至2020年的309名患者，分为三组：健康对照组（第1组，N = 51）、无急性心肌梗死（AMI）的DM患者（第2组，N = 150）和AMI的DM患者（第3组，N = 108）。我们使用压力灌注心脏磁共振（CMR）成像评估冠状动脉微血管疾病（CMD）（结果 1）、视网膜造影评估视网膜微血管疾病（RMD）（结果 2）、CMD 和 RMD（结果 3）以及无微血管疾病（w/o MD）（结果 4）。我们使用接收器操作特征（ROC）分析和多元逻辑回归评估了神经酰胺的分类性能。我们的研究小组先前确定了与大血管疾病相关的 11-神经酰胺面板：结果：糖化血红蛋白（HbA1c）的平均值为：第一组 5.1%，第二组 8.3%，第三组 7.6%。在队列中，59.5% 的患者患有 CMD，25.8% 的患者患有 RMD，18.8% 的患者同时患有 CMD 和 RMD，38.5% 的患者未患有 MD。参考神经酰胺比率的 AUC 值如下：CMD为0.66（p = 0.012），RMD为0.61（p = 0.248），CMD和RMD为0.64（p = 0.282），无/有MD为0.67（p = 0.010）。相比之下，使用 11-神经酰胺面板的 AUC 值在结果预测方面有显著改善：CMD 为 0.81（p = 0.001），RMD 为 0.73（p = 0.010），CMD & RMD 为 0.73（p = 0.04），无 MD 为 0.83（p = 0.010）。此外，血浆中 C14.0 的浓度在无/有 MD 组明显更高（p 结论：血浆中 C14.0 的浓度在无/有 MD 组明显更高（p 结论：血浆中 C14.0 的浓度在无/有 MD 组明显更高）：血浆神经酰胺是糖尿病患者健康状况和微血管疾病表型的潜在预测因子。

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Clinical Diabetes and Endocrinology

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8 weeks

期刊介绍： Clinical Diabetes and Endocrinology is an open access journal publishing within the field of diabetes and endocrine disease. The journal aims to provide a widely available resource for people working within the field of diabetes and endocrinology, in order to improve the care of people affected by these conditions. The audience includes, but is not limited to, physicians, researchers, nurses, nutritionists, pharmacists, podiatrists, psychologists, epidemiologists, exercise physiologists and health care researchers. Research articles include patient-based research (clinical trials, clinical studies, and others), translational research (translation of basic science to clinical practice, translation of clinical practice to policy and others), as well as epidemiology and health care research. Clinical articles include case reports, case seminars, consensus statements, clinical practice guidelines and evidence-based medicine. Only articles considered to contribute new knowledge to the field will be considered for publication.