English

Medical Science of Ukraine

Current

Vol. 22, No. 1, 2026

Medical Science of Ukraine

Medical Science of Ukraine

ISSN 2664-472X

EISSN 2664-4738 

Publisher: O.O. Bogomolets National Medical University



Retrieved from Vol. 22, No. 1, 2026

Serum L- and E-selectins as predictors of severity and rapid progression of diabetic retinopathy in type 2 diabetes

Received 08.10.2025, Revised 10.02.2026, Accepted 18.03.2026 Published 30.03.2026

https://doi.org/10.32345/2664-4738.1.2026.04

Anton Serdyuk

Abstract

Background. Diabetic retinopathy (DR) on the background of type 2 diabetes mellitus (DM2) is characterized by heterogeneity of the course, and the prediction of rapid progression after initial treatment requires available systemic markers of endothelial activation and inflammation. Aim: to evaluate serum levels of L selectin (LS) and E selectin (ES) as markers of DR severity and predictors of its rapid progression.
Materials and methods. In a prospective cohort study, 136 patients with DM2 and DR, staged according to WHO criteria as non-proliferative (NPDR), pre-proliferative (PPDR) and proliferative (PDR), were examined. Baseline LS/ES levels were determined by enzyme-linked immunosorbent assay. Clinical trajectory was assessed after 1-2 years, distinguishing between no/slow progression (grade 0-1) and rapid progression (grade 2) of DR. Nonparametric tests, logistic regression with adjustment for age, duration of T2DM and systolic blood pressure, and ROC analysis were used.
Results. LS and ES concentrations increased monotonically with DR stage (p < 0.001): LS – 25.95, 55.65 and 67.15 ng/ml in NPDR/PPDR/PDR; ES – 24.30, 62.30 and 70.55 ng/ml, respectively. In adjusted ordinal regression, a 10 ng/mL increase in markers was associated with progression to a more severe stage of DR (OR 3.97 for LS; OR 5.77 for ES; both p < 0.001). Their high baseline levels predicted rapid disease progression (adjusted OR per 10 ng/mL: 4.77 for LS and 2.39 for ES; both p < 0.001). LS had excellent discrimination of rapid progression of DR (AUC 0.932; threshold 40.6 ng/mL), whereas ES best identified existing PD (AUC 0.892; threshold 50.0 ng/mL).
Conclusion. LS and ES are systemic markers of DR severity and independent predictors of its rapid progression over 1-2 years, although the cutoff values require external validation

References

  1. International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation; 2021. ISBN: 978-2-930229-98-0.
  2. World Health Organization. Diabetes. Fact sheet. Updated November 14, 2024.
  3. Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology. 2021 Nov;128(11):1580-1591. doi: 10.1016/j.ophtha.2021.04.027.
  4. Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, et al. Diabetic Retinopathy Preferred Practice Pattern®. Ophthalmology. 2020 Jan;127(1):P66-P145. doi: 10.1016/j.ophtha.2019.09.025. Epub 2019 Sep 25. Erratum in: Ophthalmology. 2020 Sep;127(9):1279. doi: 10.1016/j.ophtha.2020.06.047.
  5. Wong TY, Cheung CM, Larsen M, Sharma S, Simó R. Diabetic retinopathy. Nat Rev Dis Primers. 2016 Mar 17;2:16012. doi: 10.1038/nrdp.2016.12.
  6. Forrester JV, Kuffova L, Delibegovic M. The Role of Inflammation in Diabetic Retinopathy. Front Immunol. 2020 Nov 6;11:583687. doi: 10.3389/fimmu.2020.583687.
  7. Rübsam A, Parikh S, Fort PE. Role of Inflammation in Diabetic Retinopathy. Int J Mol Sci. 2018 Mar 22;19(4):942. doi: 10.3390/ijms19040942.
  8. Tang J, Kern TS. Inflammation in diabetic retinopathy. Prog Retin Eye Res. 2011 Sep;30(5):343-58. doi: 10.1016/j.preteyeres.2011.05.002.
  9. Miyamoto K, Khosrof S, Bursell SE, Rohan R, Murata T, Clermont AC, et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10836-41. doi: 10.1073/pnas.96.19.10836.
  10. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001 Jan;158(1):147-52. doi: 10.1016/S00029440(10)63952-1.
  11. Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004 Sep;18(12):1450-2. doi: 10.1096/fj.03-1476fje.
  12. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007 Sep;7(9):678-89. doi: 10.1038/nri2156.
  13. McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015 Aug 1;107(3):331-9. doi: 10.1093/cvr/cvv154.
  14. Zarbock A, Ley K, McEver RP, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood. 2011 Dec 22;118(26):6743-51. doi: 10.1182/ blood-2011-07-343566.
  15. Karadayi K, Top C, Gülecek O. The relationship between soluble L-selectin and the development of diabetic retinopathy. Ocul Immunol Inflamm. 2003 Jun;11(2):123-9. doi: 10.1076/ocii.11.2.123.15920.
  16. MacKinnon JR, Knott RM, Forrester JV. Altered L-selectin expression in lymphocytes and increased adhesion to endothelium in patients with diabetic retinopathy. Br J Ophthalmol. 2004 Sep;88(9):1137-41. doi: 10.1136/ bjo.2003.040329.
  17. Ersanli D, Top C, Oncül O, Aydin A, Terekeci H. Relationship between serum soluble E-selectin levels and development of diabetic retinopathy in patients with type 2 diabetes. Scand J Clin Lab Invest. 2007;67(5):4749. doi: 10.1080/00365510601110148.
  18. Matsumoto K, Sera Y, Ueki Y, Inukai G, Niiro E, Miyake S. Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy. Diabet Med. 2002 Oct;19(10):822-6. doi: 10.1046/j.1464-5491.2002.00799.x.
  19. Nowak M, Wielkoszyński T, Marek B, Kos-Kudła B, Swietochowska E, Siemińska L, et al. Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy. Clin Exp Med. 2008 Sep;8(3):159-64. doi: 10.1007/s10238-008-0173-z.
  20. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013 Mar;48(3):452-8. doi: 10.1038/bmt.2012.244.
  21. Soedamah-Muthu SS, Chaturvedi N, Schalkwijk CG, Stehouwer CD, Ebeling P, Fuller JH; EURODIAB Prospective Complications Study group. Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in Type 1 diabetic patients. J Diabetes Complications. 2006 May-Jun;20(3):188-95. doi: 10.1016/j.jdiacomp.2005.06.005.
  22. Blum A, Pastukh N, Socea D, Jabaly H. Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications. Cytokine. 2018 Jun;106:76-79. doi: 10.1016/j.cyto.2017.10.014.
  23. Yao Y, Du J, Li R, Zhao L, Luo N, Zhai JY, et al. Association between ICAM-1 level and diabetic retinopathy: a review and meta-analysis. Postgrad Med J. 2019 Mar;95(1121):162-168. doi: 10.1136/postgradmedj-2018-136102.
  24. Ekelund C, Dereke J, Nilsson C, Landin-Olsson M. Are soluble E-selectin, ICAM-1, and VCAM-1 potential predictors for the development of diabetic retinopathy in young adults, 15-34 years of age? A Swedish prospective cohort study. PLoS One. 2024 Jun 6;19(6):e0304173. doi: 10.1371/journal.pone.0304173.
  25. Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holman RR, Manley SE, et al. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia. 2001 Feb;44(2):156-63. doi: 10.1007/s001250051594.
  26. Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, et al. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
  27. Muni RH, Kohly RP, Lee EQ, Manson JE, Semba RD, Schaumberg DA. Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial. JAMA Ophthalmol. 2013 Apr;131(4):514-21. doi: 10.1001/jamaophthalmol.2013.2299.
  28. Rajab HA, Baker NL, Hunt KJ, Klein R, Cleary PA, Lachin J, et al.; DCCT/EDIC Group of Investigators. The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes. J Diabetes Complications. 2015 Jan-Feb;29(1):108-14. doi: 10.1016/j.jdiacomp.2014.08.004.
  29. Boulbou MS, Koukoulis GN, Petinaki EA, Germenis A, Gourgoulianis KI. Soluble adhesion molecules are not involved in the development of retinopathy in type 2 diabetic patients. Acta Diabetol. 2004 Sep;41(3):118-22. doi: 10.1007/s00592-004-0154-y.
  30. Olson JA, Whitelaw CM, McHardy KC, Pearson DW, Forrester JV. Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration. Diabetologia. 1997 Oct;40(10):1166-71. doi: 10.1007/s001250050802.
  31. Spijkerman AM, Gall MA, Tarnow L, Twisk JW, Lauritzen E, Lund-Andersen H, et al. Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes. Diabet Med. 2007 Sep;24(9):969-76. doi: 10.1111/j.1464-5491.2007.02217.x.
Download article

Keywords:

Diabetic Retinopathy; Type 2 Diabetes Mellitus; L-Selectin; E-Selectin; Endothelial Activation; Biomarkers; Disease Progression; Risk Prediction

Pages 32-41

Suggested citation

Serdyuk, A. (2026). Serum L- and E-selectins as predictors of severity and rapid progression of diabetic retinopathy in type 2 diabetes. Medical Science of Ukraine, 22(1), 32-41. https://doi.org/10.32345/2664-4738.1.2026.04

We assign DOI (prefix: 10.32345)

ISSN 2664-472X; e-ISSN 2664-4738

National Library of Ukraine named after V. I. Vernadskyi
ResearchBib
Google Scholar
Portal
DOAJ (Directory of Open Access Journals)
Polska Bibliografia Naukowa
UlrichsWeb
Worldcat
Open Ukrainian Citation Index
erih+