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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2025; 16(9): 106002
Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.106002
Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.106002
Increased tumor necrosis factor-receptor superfamily plasma levels are associated with early renal or retinal involvement in intermediate hyperglycemia
Sebastian Mas-Fontao, Jesús Egido, Renal, Vascular and Diabetes and Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid 28040, Spain
Sebastian Mas-Fontao, Jesús Egido, Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid 28040, Spain
Sebastian Mas-Fontao, Esther Civantos, Facultad de Medicina y Biomedicina, Universidad Alfonso X, Villanueva de la Canada, Madrid 28691, Spain
Nisa Boukichou-Abdelkader, Data Science Unit, Rioja Health Foundation, Logrono 26006, La Rioja, Spain
Juan Antonio Moreno, Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba 14071, Andalusia, Spain
Carmen Gomez-Guerrero, Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma de Madrid, Madrid 28040, Spain
M Isabel López Gálvez, IOBA Reading Center, University of Valladolid, Valladolid 47011, Castille-Leon, Spain
Jaakko Tuomilehto, Department of Public Health, University of Helsinki, Helsinki 00014, Uusimaa, Finland
Marcus Lind, Department of Endocrinology, University of Gothenburg, Gothenburg 40530, Vastra Gotaland, Sweden
Rafael Gabriel, Departamento de Salud Internacional, Instituto de Salud Carlos III, Madrid 28029, Spain
Author contributions: Gabriel R, Tuomilehto J, Egido J, Mas-Fontao S contributed to conceptualization, funding acquisition; Boukichou-Abdelkader N, Mas-Fontao S contributed to data curation, formal analysis; Mas-Fontao S, Civantos E, Gálvez MIL and Early Prevention of Diabetes Complications investigators contributed to investigation; Egido J, Mas-Fontao S contributed to methodology, writing original draft; Egido Jesús contributed to project administration; Mas-Fontao S contributed to visualization; Moreno JA, Gomez-Guerrero C, Tuomilehto J, Lind M, Gabriel R contributed to writing, review and editing.
Supported by the Instituto de Salud Carlos III (ISCIII) Through the Project Co-Funded by the European Union, No. PI20-00487, No. PI23-00119 and No. PI24-01630.
Institutional review board statement: This study complies with the Declaration of Helsinki and was performed according to ethics committee approval of all national Medicine Agencies and local ethic committees of participating centers: Hospital Universitario La Paz, Madrid, Spain. Approval No. 3850 (February 01, 2013); Hellenic Republic Ministry of Health National Ethics Committee, Greece. Approval No. 74/00-01/14 (December 15, 2014); The Dean office, Istanbul Medical Faculty Ethical Board for Clinical Trials, Turkey. Approval No. 2014/495 (April 10, 2014); Etickog Odbora. Beograd, Republike Srbije, Serbia. Approval No. 61/1 (April 06, 2013); Ethics Committee of the Faculty of Medicine, University of Belgrade, Serbia. Approval No. 29/III-10 (March 07, 2013); Komisji Bioetycznej Uniwersytetu Jagiellonskiego, Poland. Approval No. BET/185/L/2014 (June 26, 2014); Executive Officer of Ethics Review Committee (RPAH) and Human Research Ethics Committee (HREC), Australia. Approval No. X13-0046 and No. HREC/13/RPAH/65 (March 12, 2014); комисия по етика “Александровска” ЕАД София, България, Bulgaria. Approval No. KИ-213/18.03.15 (March 18, 2015); Die Ethikkommission für das Bundesland Salzburg. “Landeskrankenhaus Salzburg-Universitätsklinikum der PMU, Universitätsklinik für Innere Medizin I”, Austria. Approval No. 415-E/1649/10-2014 (July 08, 2014).
Informed consent statement: All study participants gave their written informed consent prior to the participation in the study.
Conflict-of-interest statement: Tuomilehto J owns stocks in OrionPharma, Aktivolabs, Digostics and Oriola. Other authors declare no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data that support the findings of this study are available from the Early Prevention of Diabetes Complications study group upon reasonable request and with appropriate permissions. Contact: Boukichou N (nisa83_1@hotmail.com).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sebastian Mas-Fontao, PhD, FESC, Renal, Vascular and Diabetes and Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Av Reyes Católicos 2, Madrid 28040, Spain. smas@quironsalud.es
Received: February 17, 2025
Revised: March 31, 2025
Accepted: August 6, 2025
Published online: September 15, 2025
Processing time: 209 Days and 0.5 Hours
Revised: March 31, 2025
Accepted: August 6, 2025
Published online: September 15, 2025
Processing time: 209 Days and 0.5 Hours
Core Tip
Core Tip: This study identifies tumor necrosis factor (TNF) receptor superfamily members as potential early biomarkers of renal and retinal dysfunction in individuals with intermediate hyperglycemia (IH). TNF receptor 1, TNF receptor 2, and T-cell immunoglobulin and mucin domain 3 (TIM-3) are significantly associated with early-stage renal impairment, while TIM-3 shows strong predictive value for retinopathy. These findings highlight the role of inflammation in microvascular complications and suggest that integrating these biomarkers into clinical screening may improve early detection and personalized intervention strategies in IH.