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 ret...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-11-01
Series:Ophthalmology Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S266691452500168X
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author 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
author_facet 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
author_sort Siddhita A. Jadhav, MSc
collection DOAJ
description 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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spelling doaj-art-e202cdccf7114008a69a4a8604a9c98c2025-08-20T03:57:58ZengElsevierOphthalmology Science2666-91452025-11-015610087010.1016/j.xops.2025.100870Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht StudySiddhita A. Jadhav, MSc0Birke J. Benedikter, PhD1Sara B.A. Mokhtar, MSc2Frank C.T. van der Heide, MD, PhD3Govindasamy Kumaramanickavel, MD4Marleen M.J. van Greevenbroek, PhD5Carroll A.B. Webers, MD, PhD6Tos T.J.M. Berendschot, PhD7Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; University Eye Clinic, Maastricht University Medical Center +, Maastricht, the Netherlands; GenVams Trust, Chennai, IndiaMental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; University Eye Clinic, Maastricht University Medical Center +, Maastricht, the NetherlandsMental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; University Eye Clinic, Maastricht University Medical Center +, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; School for Cardiovascular Diseases, CARIM, Maastricht University, Maastricht, the NetherlandsInserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Université Paris Cité, Paris, France; Rothschild BRAINlab, Adolphe de Rothschild Foundation Hospital, Paris, FranceGenVams Trust, Chennai, IndiaDepartment of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; School for Cardiovascular Diseases, CARIM, Maastricht University, Maastricht, the NetherlandsMental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; University Eye Clinic, Maastricht University Medical Center +, Maastricht, the NetherlandsMental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; University Eye Clinic, Maastricht University Medical Center +, Maastricht, the Netherlands; Correspondence: Tos T. J. M. Berendschot, PhD, Postbox 5800, 6202 AZ, Maastricht, the Netherlands.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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.http://www.sciencedirect.com/science/article/pii/S266691452500168XDiabetic retinal neurodegenerationDiabetic retinopathySphingomyelin
spellingShingle 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
Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
Ophthalmology Science
Diabetic retinal neurodegeneration
Diabetic retinopathy
Sphingomyelin
title Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
title_full Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
title_fullStr Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
title_full_unstemmed Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
title_short Plasma Sphingomyelins as Biomarkers for Diabetic Retinal Neurodegeneration: The Maastricht Study
title_sort plasma sphingomyelins as biomarkers for diabetic retinal neurodegeneration the maastricht study
topic Diabetic retinal neurodegeneration
Diabetic retinopathy
Sphingomyelin
url http://www.sciencedirect.com/science/article/pii/S266691452500168X
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