Influence of changes in serum levels of IL-1F4, INCAM-1 and VPF on patients with diabetic retinopathy

Serum IL-1F4, INCAM-1 and VPF in diabetic retinopathy

  • Tianyang Xie Day Ward, Jiading District Central Hospital Affiliated Shanghai University of Medicine &Health Sciences
  • Qianyi Lu Endocrinology Department, The First Hospital of Lanzhou University
  • Wei Zhu Endocrinology Department, The First Hospital of Lanzhou University
  • Dan Huang Department of Ophthalmology, Jiading District Central Hospital Affiliated Shanghai University of Medicine &Health Sciences
Keywords: Type 2 diabetes, Diabetic retinopathy, Interleukin-1 family member 4, Intercellular adhesion molecule-1 on endothelial cells, Vascular Permeability Factor, Prognostic analysis

Abstract


[Objective] To explore the relationships between serum Interleukin-1 family member 4 (IL-1F4), Intercellular adhesion molecule-1 on endothelial cells (INCAM-1), and Vascular Permeability Factor (VPF) levels and disease progression and prognosis in patients with diabetic retinopathy (DR).

[Methods] 538 individuals with type 2 diabetes mellitus (T2DM) who were admitted to our hospital between February 2022 and February 2025 were chosen retrospectively. Based on their DR consequences, these patients were split into two groups: 178 cases of T2DM and 360 cases of DR. The evolution of these DR patients' illnesses led to further division into two groups: a non-PDR (NPDR) group (134 instances) and a proliferative DR (PDR) group (226 cases). Additionally, 134 healthy volunteers who underwent examinations throughout the same time frame made up the control group. The differences in clinical data and serum levels of IL-1F4, INCAM-1, and VPF among the different groups were compared; the correlations among serum levels of IL-1F4, INCAM-1, and VPF were analyzed, and to determine the variables affecting the course of DR. Based on the occurrence of visual impairment, DR patients were divided into two groups after a year of follow-up: those with a favorable prognosis (256 patients) and those with a poor prognosis (104 patients). Differences in clinical data and serum levels of IL-1F4, INCAM-1, and VPF among DR patients with different prognoses were compared. The factors influencing the poor prognosis of diabetic retinopathy (DR) were identified using multivariate logistic regression analysis, and the predictive value of serum IL-1F4, INCAM-1, and VPF for the poor prognosis of DR was assessed using receiver operating characteristic (ROC) curves.

[Results] The fasting blood glucose (FPG), glycosylated hemoglobin (Hb A1c), IL-1F4, INCAM-1, and VPF levels in the control group, T2DM group, NPDR group, and PDR group increased successively (P < 0.05), and the duration of diabetes in the T2DM group, NPDR group, and PDR group increased successively (P < 0.05). The serum levels of IL-1F4, INCAM-1, and VPF in individuals with DR showed positive relationships (r = 0.500, 0.489, and 0.564, respectively; P < 0.05) according to Pearson analysis. High levels of FPG, Hb A1c, IL-1F4, INCAM-1, and VPF, together with a longer duration of diabetes, were all found to influence the advancement of DR (P < 0.05) by multivariate logistic regression analysis. Groups with poor prognoses were older than those with good prognoses. Body mass index, FPG, Hb A1c, IL-1F4, INCAM-1, and VPF were higher in the group with a bad prognosis than in the group with a good prognosis. Additionally, the duration of diabetes was longer in the poor prognosis group (P < 0.05). Multivariate logistic regression analysis revealed that a longer duration of diabetes, as well as high levels of FPG, Hb A1c, IL-1F4, INCAM-1, and VPF, were all variables affecting how DR progressed (P < 0.05). The areas under the curve (AUCs) for forecasting a bad prognosis in individuals with diabetic retinopathy (DR) were found using ROC curve analysis. according to serum levels of IL-1F4, INCAM-1, and VPF were 0.771, 0.823, and 0.766, respectively. When these three indicators were combined, the area under the curve (AUC) for predicting a poor prognosis in DR patients was 0.873, which was higher than the AUC for any one sign alone (P < 0.05).

[Conclusion] Serum IL-1F4, INCAM-1 and VPF may jointly participate in the process of DR. The elevated levels of these cytokines are closely related to the progression of DR and poor prognosis. Serum IL-1F4, INCAM-1 and VPF can be used as effective indicators for evaluating the progression of DR and visual disability.

References

1.Tesfaye H, Paik JM, Roh M, Htoo PT, Zakoul H, Schmedt N, Koeneman L, Wexler DJ, Patorno E. Empagliflozin and the Risk of Retinopathy in Patients With Type 2 Diabetes. JAMA Ophthalmol. 2025 Jan 1;143(1):62-71. doi: 10.1001/jamaophthalmol.2024.5219. PMID: 39636645; PMCID: PMC11622102.
2.Song SH. Young-onset type 2 diabetes and retinopathy: evidence of an adverse phenotype. BMJ Open Diabetes Res Care. 2024 Jan 2;12(1):e003899. doi: 10.1136/bmjdrc-2023-003899. PMID: 38167607; PMCID: PMC10773418.
3.Liang YY, He Y, Wang J, Liu Y, Ai S, Feng H, Zhu C, Li H, Zhou Y, Zhang J, Zhang J, Qi L. Social Isolation, Loneliness, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes Mellitus. Am J Kidney Dis. 2024 Nov;84(5):557-566.e1. doi: 10.1053/j.ajkd.2024.05.004. Epub 2024 Jun 24. PMID: 38925507.
4.Cai K, Liu YP, Wang D. Prevalence of diabetic retinopathy in patients with newly diagnosed type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023 Jan;39(1):e3586. doi: 10.1002/dmrr.3586. Epub 2022 Nov 14. PMID: 36286346.
5.Shi Y, Fan X, Zhang K, Ma Y. Association of the endothelial nitric oxide synthase (eNOS) 4a/b polymorphism with the risk of incident diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and updated meta-analysis. Ann Med. 2023 Dec;55(1):2226908. doi: 10.1080/07853890.2023.2226908. Erratum in: Ann Med. 2023 Dec;55(1):2245611. doi: 10.1080/07853890.2023.2245611. PMID: 37353997; PMCID: PMC10291908.
6.Liang Y, Zhang X, Mei W, Li Y, Du Z, Wang Y, Huang Y, Zeng X, Lai C, Wang S, Fang Y, Zhang F, Zang S, Sun W, Yu H, Hu Y. Predicting vision-threatening diabetic retinopathy in patients with type 2 diabetes mellitus: Systematic review, meta-analysis, and prospective validation study. J Glob Health. 2024 Oct 11;14:04192. doi: 10.7189/jogh.14.04192. PMID: 39391902; PMCID: PMC11467770.
7.Li Z, Yuan Y, Qi Q, Wang Q, Feng L. Relationship between dyslipidemia and diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Syst Rev. 2023 Aug 24;12(1):148. doi: 10.1186/s13643-023-02321-2. PMID: 37620980; PMCID: PMC10463379.
8.Buckley AJ, Tan GD, Gruszka-Goh M, Scanlon PH, Ansari I, Suliman SGI. Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study. Diabetologia. 2025 Sep;68(9):2069-2076. doi: 10.1007/s00125-025-06466-8. Epub 2025 Jul 10. PMID: 40637847; PMCID: PMC12361273.
9.Basir H, Nugrahani ASD, Aman AM, Bakri S, Rasyid H, Umar H, H P F, Ichsan AM, Zainuddin AA. The association between fibroblast growth factor 21 with diabetes retinopathy among type 2 diabetes mellitus patients: a systematic review, meta-analysis, and meta-regression. PeerJ. 2024 Dec 13;12:e18308. doi: 10.7717/peerj.18308. PMID: 39687000; PMCID: PMC11648683.
10.Guo H, Han F, Qu JR, Pan CQ, Sun B, Chen LM. Scoring and validation of a simple model for predicting diabetic retinopathy in patients with type 2 diabetes based on a meta-analysis approach of 21 cohorts. Ann Med. 2024 Dec;56(1):2413920. doi: 10.1080/07853890.2024.2413920. Epub 2024 Oct 11. PMID: 39392052; PMCID: PMC11485693.
11.Cheng B, Wu A, Zhou X. Association Between VEGF-460C/T Gene Polymorphism and Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis. Horm Metab Res. 2024 Mar;56(3):214-222. doi: 10.1055/a-2223-2790. Epub 2023 Dec 5. PMID: 38052425.
12.Chen M, Wang Y, Feng P, Liang Y, Liu Q, Yang M, Lu C, Shi P, Cheng J, Ji A, Zheng Q. Association between Age at Type 2 Diabetes Onset and Diabetic Retinopathy: A Double-Center Retrospective Study. J Diabetes Res. 2023 Jan 23;2023:5919468. doi: 10.1155/2023/5919468. PMID: 36726740; PMCID: PMC9886461.
13.Wang Q, Cheng H, Jiang S, Zhang L, Liu X, Chen P, Liu J, Li Y, Liu X, Wang L, Li Z, Cai G, Chen X, Dong Z. The relationship between diabetic retinopathy and diabetic nephropathy in type 2 diabetes. Front Endocrinol (Lausanne). 2024 Jan 26;15:1292412. doi: 10.3389/fendo.2024.1292412. PMID: 38344659; PMCID: PMC10853456.
14.Jiao X, Peng P, Zhang Q, Shen Y. Glucagon-Like Peptide-1 Receptor Agonist and Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials. Clin Drug Investig. 2023 Dec;43(12):915-926. doi: 10.1007/s40261-023-01319-x. Epub 2023 Nov 8. PMID: 37938535.
15.Yen FS, Wei JC, Yu TS, Hung YT, Hsu CC, Hwu CM. Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes. JAMA Netw Open. 2023 Dec 1;6(12):e2348431. doi: 10.1001/jamanetworkopen.2023.48431. PMID: 38117497; PMCID: PMC10733799.
16.Bushi G, Gaidhane AM, Vadia N, Menon SV, Chennakesavulu K, Panigrahi R, Shabil M, Rani A, Sah S, Yappalparvi A, Goh KW, Jena D. Creatinine as a predictor of proliferative diabetic retinopathy among patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Int Urol Nephrol. 2025 Dec;57(12):4119-4129. doi: 10.1007/s11255-025-04590-3. Epub 2025 Jun 3. PMID: 40461778.
17.Yang Z, Liu Q, Wen D, Yu Z, Zheng C, Gao F, Chen C, Hu L, Shi Y, Zhu X, Liu J, Shao Y, Li X. Risk of diabetic retinopathy and retinal neurodegeneration in individuals with type 2 diabetes: Beichen Eye Study. Front Endocrinol (Lausanne). 2023 May 3;14:1098638. doi: 10.3389/fendo.2023.1098638. PMID: 37206443; PMCID: PMC10191177.
18.Borderie G, Foussard N, Larroumet A, Blanco L, Barbet-Massin MA, Ducos C, Rigo M, Arab LR, Domenge F, Mohammedi K, Ducasse E, Caradu C, Delyfer MN, Korobelnik JF, Rigalleau V. Diabetic retinopathy relates to the incidence of foot ulcers and amputations in type 2 diabetes. Diabetes Metab Res Rev. 2023 Mar;39(3):e3605. doi: 10.1002/dmrr.3605. Epub 2023 Jan 12. PMID: 36575816.
19.Zhang Y, Song X, Qi T, Gao S, Sun C, Yang J, Zhou X. Association between lipocalin-2 levels and diabetic retinopathy in patients with overweight/obese type 2 diabetes mellitus. Ir J Med Sci. 2023 Dec;192(6):2785-2792. doi: 10.1007/s11845-023-03365-y. Epub 2023 Apr 18. PMID: 37069380.
20.Kim Y, Hyun C, Lee M. Discovering potential pathways between type 2 diabetes mellitus and diabetic retinopathy: A big data analysis of the South Korean National Sample Cohort. Medicine (Baltimore). 2023 Aug 4;102(31):e34576. doi: 10.1097/MD.0000000000034576. PMID: 37543803; PMCID: PMC10402935.
21.Ortiz-Seller A, Real JT, Morcillo E, Ortiz JL. Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials. J Diabetes Complications. 2026 Jan;40(1):109234. doi: 10.1016/j.jdiacomp.2025.109234. Epub 2025 Nov 26. PMID: 41314124.
22.Maddaloni E, Coraggio L, Amendolara R, Baroni MG, Cavallo MG, Copetti M, Cossu E, D'Angelo P, D'Onofrio L, Cosmo S, Leonetti F, Morano S, Morviducci L, Napoli N, Prudente S, Pugliese G, Park K, Holman RR, Trischitta V, Buzzetti R; SUMMER Study in Diabetes Group. Association of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease and retinopathy in type 2 diabetes. Diabetes Metab Res Rev. 2023 Jul;39(5):e3632. doi: 10.1002/dmrr.3632. Epub 2023 Mar 20. PMID: 36880127.
23.Oktem EO, Sayman D, Ayyildiz S, Oktem Ç, Ipek L, Ayyildiz B, Aslan F, Altindal EU, Yagci N, Dikici R, Karaca R, Cankaya Ş, Avnioglu S, Velioglu HA, Yulug B. Cognitive Function Deficits Associated With Type 2 Diabetes and Retinopathy: Volumetric Brain MR Imaging Study. Brain Behav. 2025 Mar;15(3):e70387. doi: 10.1002/brb3.70387. PMID: 40022286; PMCID: PMC11870829.
24.Yueh MP, Kao SK, Chen JW, Huang JC, Chen HS, Wu TE. Psoriasis and risk of diabetic retinopathy in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2025 Nov;229:112912. doi: 10.1016/j.diabres.2025.112912. Epub 2025 Sep 18. PMID: 40975177.
25.Chen Y, Li M, Wang Y, Fu J, Liu X, Zhang Y, Liu L, Ta S, Lu Z, Li Z, Zhou J, Li X. Association between Severity of Diabetic Retinopathy and Cardiac Function in Patients with Type 2 Diabetes. J Diabetes Res. 2023 Jun 7;2023:6588932. doi: 10.1155/2023/6588932. PMID: 37323224; PMCID: PMC10266918.
26.Li X, Hao W, Lin S, Yang N. Association between AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes: a cross-sectional investigation. Front Endocrinol (Lausanne). 2024 Apr 3;15:1361707. doi: 10.3389/fendo.2024.1361707. PMID: 38633757; PMCID: PMC11021722.
27.Wang Y, Lu J, Ni J, Wang M, Shen Y, Lu W, Zhu W, Bao Y, Rodbard D, Vigersky RA, Jia W, Zhou J. Association between glycemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study. Diabetes Obes Metab. 2023 Sep;25(9):2457-2463. doi: 10.1111/dom.15068. Epub 2023 Jun 23. PMID: 37353345.
28.Yan J, Li B, Chen Y, Gu C, Dai G, Zhang Q, Zheng Z, Luo D, Zhao S, Zhou C. Prevalence and predictors of developing vision-threatening diabetic retinopathy within the first three years of type 2 diabetes. Front Endocrinol (Lausanne). 2023 Dec 20;14:1305378. doi: 10.3389/fendo.2023.1305378. PMID: 38192422; PMCID: PMC10773727.
Published
2026/05/28
Section
Original paper