血浆鞘磷脂作为糖尿病视网膜神经变性的生物标志物：马斯特里赫特研究

IF 4.6 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-06-27 DOI:10.1016/j.xops.2025.100870

Siddhita A. Jadhav MSc , Birke J. Benedikter PhD , Sara B.A. Mokhtar MSc , Frank C.T. van der Heide MD, PhD , Govindasamy Kumaramanickavel MD , Marleen M.J. van Greevenbroek PhD , Carroll A.B. Webers MD, PhD , Tos T.J.M. Berendschot PhD

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引用次数: 0

摘要

目的phingomyelin （SM）可能在糖尿病视网膜病变早期发挥作用。糖尿病视网膜病变的早期诊断对于预防与此病相关的不可逆视力丧失至关重要。本研究旨在探讨SM与糖尿病视网膜病变的关键指标，即视网膜神经退行性变之间的关系，包括角膜神经测量、视网膜层厚度和平均视网膜敏感性。了解这些关系可能有助于确定预防或减缓糖尿病视网膜病变进展的早期生物标志物和治疗靶点。设计：我们使用来自马斯特里赫特研究（Maastricht Study）的数据，这是一项基于人群的大型观察队列研究，对2型糖尿病（T2DM）患者进行了过采样。本研究检测了3个研究组的SM水平：(1)糖代谢正常的个体；(2)前驱糖尿病;(3) T2DM。方法采用南丁格尔健康中心的核磁共振平台测定各组血浆SM水平。主要结果和测量方法进行线性回归分析，评估血浆SM总量（决定因素）与视网膜神经变性指标（结果）之间的联系，包括角膜神经测量、平均视网膜敏感性和视网膜厚度，同时调整影响SM代谢的潜在混杂因素。结果在3598例受试者中，T2DM患者血浆中总SM的平均水平显著降低(P <；0.001)高于糖尿病前期患者和对照组，即使在使用降脂药物分层后也是如此。在回归分析中，经过充分调整后，较低水平的SM与平均视网膜敏感度降低相关：右眼（n = 1934）的β（95%置信区间）为0.088(0.012,0.164)，左眼（n = 1925）的β为0.111（0.033,0.189）。然而，与视网膜神经退行性变的其他指标无显著相关性。结论血浆SMs水平较低与糖尿病患者视网膜敏感性降低有关，表明其参与糖尿病视网膜早期神经退行性改变。这些发现表明，SMs可以作为潜在的生物标志物，在糖尿病早期检测糖尿病视网膜神经变性。然而，进一步的研究是必要的，以阐明所涉及的生物学途径，并评估SMs作为临床生物标志物的有效性。财务披露作者在本文中讨论的任何材料中没有专有或商业利益。

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Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study

Objective

Sphingomyelin (SM) may play a role in the early stages of diabetic retinopathy. Early diagnosis of diabetic retinopathy is crucial for preventing the irreversible vision loss associated with this condition. This study aimed to examine the link between SM and key indicators of diabetic retinopathy, namely retinal neurodegeneration, including corneal nerve measures, retinal layer thickness, and mean retinal sensitivity. Understanding these relationships may help identify early biomarkers and therapeutic targets for preventing or slowing the progression of diabetic retinopathy.

Design

We used data from the Maastricht Study, a large population-based observational cohort with oversampling of individuals with type 2 diabetes mellitus (T2DM).

Subjects

In this study, SM levels were examined across 3 study groups: (1) individuals with normal glucose metabolism; (2) prediabetes; and (3) T2DM.

Methods

Fasting plasma SM levels were measured using the nuclear magnetic resonance platform from Nightingale Health.

Main Outcomes and Measures

Linear regression analysis was conducted to assess the link between total plasma SM (determinant) and indicators of retinal neurodegeneration (outcomes), including corneal nerve measures, mean retinal sensitivity, and retinal thickness, while adjusting for potential confounders affecting SM metabolism.

Results

Among the 3598 individuals examined, the average plasma levels of total SM were significantly lower in individuals with T2DM (P < 0.001) than those with prediabetes and the control group, even after stratification by lipid-modifying medication usage. In regression analysis, after full adjustment, lower levels of SM were associated with reduced mean retinal sensitivity: β (95% confidence interval) for the right eye (n = 1934), 0.088 (0.012, 0.164) and for the left eye (n = 1925), 0.111 (0.033, 0.189). However, no significant correlations were found with other indicators of retinal neurodegeneration.

Conclusions

Lower levels of plasma SMs were linked to reduced retinal sensitivity in individuals with diabetes, indicating their involvement in early neurodegenerative alterations in the diabetic retina. These findings suggest that SMs could be explored as potential biomarkers for detecting diabetic retinal neurodegeneration at an early stage of diabetes. However, further research is essential to clarify the biological pathways involved and to evaluate the effectiveness of SMs as clinical biomarkers.