Blood selectin levels as a predictive factor for diabetic retinopathy and diabetic macular edema in type 2 diabetes
DOI:
https://doi.org/10.31288/oftalmolzh202331926Keywords:
diabetic retinopathy, diabetic macular edema, type 2 diabetes mellitus, soluble selectins, regression predictive modelAbstract
Background: Diabetes mellitus (DM) is still a noninfectious global pandemic. Diabetic retinopathy (DR) is one of the most common and socially significant complications of both type 1 and type 2 diabetes. Predicting the probability of DR progression and potential diabetic macular edema (DME) development is still important. Currently available predictive models include a wide number of predictors, and such predictors as blood selectin levels seem to be promising.
Purpose: To determine relationships between blood levels of selectins and DR progression and DME development in patients with T2DM, and to develop particular predictive models.
Material and Methods: Of the 124 patients (124 eyes) involved into this study, 95 (95 eyes) had T2DM and retinopathy (group 1 of 29 eyes with mild non-proliferative DR (NPDR); group 2 of 35 eyes with moderate or severe non-proliferative NPDR; and group 3 of 31 eyes with proliferative DR (PDR)), and 29 (29 eyes) had no diabetes (controls). Patients underwent a routine eye examination and spectral domain optical coherence tomography (SD-OCT) to determine central retinal thickness (CRT). The presence of DME was based on an increased macular thickness in the Early Treatment Diabetic Retinopathy Study (ETDRS) subfields compared to the upper limit of normal for patient's age and gender. Enzyme-linked immunosorbent assay (ELISA) kits from Invitrogen Thermo Fisher Scientific (USA) were used to determine selectin levels in blood. Statistical analyses were conducted using MedStat and MedCalc v.15.1 (MedCalc Software bvba) software.
Results: There was a statistically significant tendency for an increase in progression of DR to be accompanied by an increase in blood selectin levels. In the presence of DME, blood LS levels were statistically significantly increased in mild NPDR; blood PS levels, in PDR; and blood ES levels, in all stages of DR. A regression model for predicting the progression of DR was built. In the model developed, diabetes duration and blood selectin levels were positively correlated, while HbA1c level was inversely correlated with DR progression. The model was found to be adequate R2adjust = 0.84; F = 97.9, p < 0.001), demonstrating high correlation of the selected independent variables with the stage of DR. The calculated Y index may be considered a quantitative reflection of the severity of DR. A patient is predicted to have mild NPDR (with a prediction accuracy of 86.2%) if Y < 1.5, moderate of severe NPDR (with a prediction accuracy of 88.6%) if 1.5 ≤ Y < 2.35, and PDR (with a prediction accuracy of 100%) if Y ≥ 2.35. A regression model for predicting the development of DME was built, with CRT and blood ES level found to increase the risk of the development of DME. A high AUC value for the ROC curve (AUC = 0.97; 95% CI, 0.92-0.99) indicated a very strong correlation of the risk of DME development with the levels of selected independent variables. In addition, sensitivity and specificity values at the optimal cut-off point were 93.2% (95% CI, 83.5%-98.1%) and 92.3% (95% CI, 83.0%-97.5%), respectively.
Conclusion: Our findings confirmed the current view that high blood selectin levels are important in the presence of T2DM and related to major pathogenetic mechanisms of microvascular complications, and blood selectin levels can be considered predictors of the progression of DR as well as the development of DME.
References
TeoZL, ThamYC, YuM, CheeML, RimTH, CheungN, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology.2021Nov;128(11):1580-1591. https://doi.org/10.1016/j.ophtha.2021.04.027
Lin KY, Hsih WH, Lin YB, Wen CY, Chang TJ. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig. 2021 Aug;12(8):1322-1325. https://doi.org/10.1111/jdi.13480
Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs - an extension of the modified Airlie house classification: ETDRS report № 10. Ophthalmology. 2020 Apr;127(4S): 99-119. https://doi.org/10.1016/j.ophtha.2020.01.030
Ghamdi AHA. Clinical Predictors of Diabetic Retinopathy Progression; A Systematic Review. Curr Diabetes Rev. 2020;16(3):242-7. https://doi.org/10.2174/1573399815666190215120435
Mogilevskyy SYu, Panchenko IuO, Ziablitsev SV. New risk factors for post-surgical recurrent diabetic maculopathy in type 2 diabetes mellitus. J.ophthalmol. (Ukraine). 2019;5:9-17. https://doi.org/10.31288/oftalmolzh20195917
Rangasamy S, McGuire PG, Das A. Diabetic retinopathy and inflammation: novel therapeutic targets. Middle East Afr J Ophthalmol. 2012 Jan;19(1):52-9. https://doi.org/10.4103/0974-9233.92116
Cappenberg A, Kardell M, Zarbock A. Selectin-Mediated Signaling-Shedding Light on the Regulation of Integrin Activity in Neutrophils. Cells. 2022 Apr 12;11(8):1310. https://doi.org/10.3390/cells11081310
Rahman I, Collado Sánchez A, Davies J, Rzeniewicz K, Abukscem S, Joachim J, et al. L-selectin regulates human neutrophil transendothelial migration. J Cell Sci. 2021 Feb 8;134(3):jcs250340. https://doi.org/10.1242/jcs.250340
Mastej K, Adamiec R. Stezenie sL-selektyny w surowicy krwi oraz ekspresja L-selektyny na powierzchni leukocytów chorych z cukrzyca typu 2 [Serum level of sL-selectin and leukocyte surface expression of L-selectin in patients with type 2 diabetes]. Przegl Lek. 2011;68(3):140-5. Polish.
Kasza M, Meleg J, Vardai J, Nagy B Jr, Szalai E, Damjanovich J, et al. Plasma E-selectin levels can play a role in the development of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2017 Jan;255(1):25-30. https://doi.org/10.1007/s00417-016-3411-1
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. https://doi.org/10.1111/j.1464-5491.2007.02217.x
Kutlar A, Embury SH. Cellular adhesion and the endothelium: P-selectin. Hematol Oncol Clin North Am. 2014 Apr;28(2):323-39. https://doi.org/10.1016/j.hoc.2013.11.007
Liu Z, Miner JJ, Yago T, Yao L, Lupu F, Xia L, McEver RP. Differential regulation of human and murine P-selectin expression and function in vivo. J Exp Med. 2010 Dec 20;207(13):2975-87. https://doi.org/10.1084/jem.20101545
Ogata N, Nomura S, Shouzu A, Imaizumi M, Arichi M, Matsumura M. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy. Diabetes Res Clin Pract. 2006 Sep;73(3):241-8. https://doi.org/10.1016/j.diabres.2006.01.014
Guryanov VG, Lyakh YuE, Pariy VD, Korotkyi OV, Chalyi OV, Chalyi KO, Tsekhmister YaV. Posibnyk z biostatystyky. Analiz rezulʹtativ medychnykh doslidzhenʹ u paketi EZR (R-statistics) [Handbook of Biostatistics. Analysis of the results of medical research in the package EZR (R-statistics)]. Kyiv: News. 2018: 208. Ukrainian.
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. https://doi.org/10.1076/ocii.11.2.123.15920
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;106:76-9. https://doi.org/10.1016/j.cyto.2017.10.014
Tryggestad JB, Shah RD, Braffett BH, Bacha F, Gidding SS, Gubitosi-Klug RA, et al. TODAY Study Group. Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study. Pediatr Diabetes. 2020 Sep;21(6):923-31.https://doi.org/10.1111/pedi.13062
Yun MR, Im DS, Lee JS, Son SM, Sung SM, Bae SS, Kim CD. NAD(P)H oxidase-stimulating activity of serum from type 2 diabetic patients with retinopathy mediates enhanced endothelial expression of E-selectin. Life Sci. 2006 Apr 25;78(22):2608-14. https://doi.org/10.1016/j.lfs.2005.10.044
Bavbek N, Kargili A, Kaftan O, Karakurt F, Kosar A, Akcay A. Elevated concentrations of soluble adhesion molecules and large platelets in diabetic patients: are they markers of vascular disease and diabetic nephropathy? Clin Appl Thromb Hemost. 2007 Oct;13(4):391-7. https://doi.org/10.1177/1076029607303615
Penman A, Hoadley S, Wilson JG, Taylor HA, Chen CJ, Sobrin L. P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans. Am J Ophthalmol. 2015 Jun;159(6):1152-1160.e2. https://doi.org/10.1016/j.ajo.2015.03.008
Wang Q, Zeng N, Tang H, Yang X, Yao Q, Zhang L, et al. Diabetic retinopathy risk prediction in patients with type 2 diabetes mellitus using a nomogram model. Front Endocrinol (Lausanne). 2022 Nov 16;13:993423. https://doi.org/10.3389/fendo.2022.993423
Gabrielle PH, Massin P, Arnould L, Couturier A, Bouché-Pillon J, Maupin E, et al. Development of a 1-year risk-prediction nomogram for good functional response with anti-VEGF agents in naive diabetic macular oedema. Acta Ophthalmol. 2020 Dec;98(8):e975-e982. https://doi.org/10.1111/aos.14428
Bartol-Puyal FA, Isanta C, Verdes G, Ruiz-Moreno Ó, Calvo P, Pablo L. Influence of inflammatory plasma biomarkers on choroidal thickness in type 2 diabetes mellitus. Eur J Ophthalmol. 2023 Jan;33(1):468-82. https://doi.org/10.1177/11206721221124691
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