Jadhav Siddhita A, Benedikter Birke J, Mokhtar Sara B A, van der Heide Frank C T, Kumaramanickavel Govindasamy, van Greevenbroek Marleen M J, Webers Carroll A B, Berendschot Tos T J M
Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
University Eye Clinic, Maastricht University Medical Center +, Maastricht, the Netherlands.
Ophthalmol Sci. 2025 Jun 27;5(6):100870. doi: 10.1016/j.xops.2025.100870. eCollection 2025 Nov-Dec.
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.
We used data from the Maastricht Study, a large population-based observational cohort with oversampling of individuals with type 2 diabetes mellitus (T2DM).
In this study, SM levels were examined across 3 study groups: (1) individuals with normal glucose metabolism; (2) prediabetes; and (3) T2DM.
Fasting plasma SM levels were measured using the nuclear magnetic resonance platform from Nightingale Health.
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.
Among the 3598 individuals examined, the average plasma levels of total SM were significantly lower in individuals with T2DM ( < 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.
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.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
鞘磷脂（SM）可能在糖尿病视网膜病变的早期阶段发挥作用。糖尿病视网膜病变的早期诊断对于预防与此病症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之间的联系，即视网膜神经变性，包括角膜神经测量、视网膜层厚度和平均视网膜敏感度。了解这些关系可能有助于识别早期生物标志物和治疗靶点，以预防或减缓糖尿病视网膜病变的进展。
我们使用了马斯特里赫特研究的数据，这是一个基于人群的大型观察性队列，对2型糖尿病（T2DM）患者进行了过度抽样。
在本研究中，对3个研究组的SM水平进行了检测：（1）葡萄糖代谢正常的个体；（2）糖尿病前期；（3）T2DM。
使用Nightingale Health的核磁共振平台测量空腹血浆SM水平。
进行线性回归分析，以评估总血浆SM（决定因素）与视网膜神经变性指标（结局）之间的联系，包括角膜神经测量、平均视网膜敏感度和视网膜厚度，同时对影响SM代谢的潜在混杂因素进行校正。
在3598名研究对象中，即使按使用调脂药物进行分层后，T2DM患者的总SM平均血浆水平仍显著低于糖尿病前期患者和对照组（<0.001）。在回归分析中，经过全面校正后，较低的SM水平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）为0.1ll（0.033，0.189）。然而，未发现与视网膜神经变性的其他指标有显著相关性。
糖尿病患者血浆SM水平较低与视网膜敏感度降低有关，表明其参与了糖尿病视网膜早期神经变性改变。这些发现表明，SM可作为在糖尿病早期检测糖尿病视网膜神经变性的潜在生物标志物进行探索。然而，有必要进一步研究以阐明其中涉及的生物学途径，并评估SM作为临床生物标志物的有效性。
作者对本文讨论的任何材料均无所有权或商业利益。
