{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:01:10Z","timestamp":1790596870922,"version":"4.1.0"},"reference-count":30,"publisher":"Centre for Evaluation in Education and Science (CEON\/CEES)","issue":"5","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/BY\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Biochemistry"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Background: Adipocytokines, along with macrophages infiltrating adipose tissue, contribute to chronic low-grade inflammation, which leads to insulin resistance and type 2 diabetes. Understanding insulin resistance in non-diabetic individuals and its cellular mechanisms is key for developing effective treatments and improving current protocols. This study aimed to investigate the levels of Retinol Binding Protein 4 (RBP4), Lipocalin-2, and high-sensitivity C-reactive protein (hsCRP) in individuals with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). Methods: This prospective case-control study included individuals with IFG, IGT, and newly diagnosed T2DM. Routine laboratory tests, including fasting blood glucose, insulin, HbA1c, and lipid profiles, were collected and analysed. RBP4, Lipocalin-2, and hsCRP levels were measured using the ELISA method. Results: Significant differences were found in fasting blood glucose, insulin, triglycerides, total cholesterol, and HOMA-IR values among the study groups. hsCRP levels were significantly elevated in the IGT and T2DM groups compared to controls, while RBP4 and Lipocalin-2 levels showed no significant differences. A positive correlation was observed between hsCRP and HbA1c in the IFG group, as well as between hsCRP and Lipocalin-2 in the T2DM group. Conclusions: This study demonstrates that hsCRP and Lipocalin-2 are associated with early glucose metabolism abnormalities and may serve as markers for insulin resistance and inflammation in prediabetes and T2DM. Future research is needed to clarify the roles of these biomarkers and their potential as therapeutic targets in diabetes prevention and treatment.<\/jats:p>","DOI":"10.5937\/jomb0-57001","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:03:10Z","timestamp":1744167790000},"page":"1067-1073","source":"Crossref","is-referenced-by-count":4,"title":["The role of inflammatory biomarkers RBP4, Lipocalin-2, and hsCRP in prediabetes and type 2 diabetes mellitus"],"prefix":"10.5937","volume":"44","author":[{"suffix":"Vesile","given":"Diker","family":"Ornek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozden","family":"Serin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Ebru","given":"Ertug","family":"Yorulmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Baytekin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman","family":"Oguz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcven\u00e7","family":"G\u00fcvenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3964","reference":[{"key":"ref1","unstructured":"International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: 2021. Available at: https:\/\/www.diabetesatlas.org;"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Asgari S, Masrouri S, Khalili D, Azizi F Hadaegh F Differences in the impact of impaired glucose status on clinical outcomes in younger and older adults: Over a decade of follow-up in the Tehran lipid and glucose study. Front Cardiovasc Med 2022 Oct 31; 9: 1018403;","DOI":"10.3389\/fcvm.2022.1018403"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol 2016 Dec; 231(3): R77-R99;","DOI":"10.1530\/JOE-16-0211"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Tsuji T Tseng YH. Adipose tissue-derived lipokines in metabolism. Curr Opin Genet Dev 2023 Aug; 81 : 102089;","DOI":"10.1016\/j.gde.2023.102089"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Kirichenko TV Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV The Role of Adipokines in Inflammatory Mechanisms of Obesity. Int J Mol Sci 2022 Nov 29; 23(23): 14982;","DOI":"10.3390\/ijms232314982"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Li Y Liu Y Liu S, Gao M, Wang W, Chen K, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther 2023 Apr 10; 8(1): 152;","DOI":"10.1038\/s41392-023-01400-z"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Steinhoff JS, Lass A, Schupp M. Biological Functions of RBP4 and Its Relevance for Human Diseases. Front Physiol 2021 Mar 11; 12: 659977;","DOI":"10.3389\/fphys.2021.659977"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Olsen T Blomhoff R. Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies. Adv Nutr 2020 May 1; 11(3): 644-66;","DOI":"10.1093\/advances\/nmz131"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Moraes-Vieira PM, Yore MM, Dwyer PM, Syed I, Aryal P Kahn BB. RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab 2014 Mar 4; 19(3): 512-26;","DOI":"10.1016\/j.cmet.2014.01.018"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Moraes-Vieira PM, Yore MM, Sontheimer-Phelps A, Castoldi A, Norseen J, Aryal P Simonyt\u00e9 Sj\u00f4din K, Kahn BB. Retinol binding protein 4 primes the NLRP3 inflammasome by signaling through Toll-like receptors 2 and 4. Proc Natl Acad Sci U S A 2020 Dec 8; 117(49): 31309-18;","DOI":"10.1073\/pnas.2013877117"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Xia Q, Du Z, Chen M, Zhou X , Bai W, Zheng X, et al. A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer. Mol Oncol 2023 Nov; 17(11): 2451-71;","DOI":"10.1002\/1878-0261.13529"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Bhusal A, Lee WH, Suk K. Lipocalin-2 in Diabetic Complications of the Nervous System: Physiology, Pathology, and Beyond. Front Physiol 2021 Feb 5; 12: 638112;","DOI":"10.3389\/fphys.2021.638112"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Mierzynski R, Poniedziatek-Czajkowska E, Dtuski D, Kaminski M, Mierzynska A, Leszczynska-Gorzelak B. The Potential Role of Chemerin, Lipocalin 2, and Apelin in the Diagnosis and Pathophysiology of Gestational Diabetes Mellitus. J Diabetes Res 2021 Jun 9; 2021: 5547228;","DOI":"10.1155\/2021\/5547228"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Badimon L, Pena E, Arderiu G, Padro T, Slevin M, Vilahur G, et al. C-Reactive Protein in Atherothrombosis and Angiogenesis. Front Immunol 2018 Mar 2; 9: 430;","DOI":"10.3389\/fimmu.2018.00430"},{"key":"ref15","unstructured":"Ridker PM, Cannon CP Morrow D, Rifai N, Rose LM, McCabe CH, et al. Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE iT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352: 20-8;"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Guo L, Lv H, Wang J, Zhang B, Zhu Y, Zhang X , et al. Predictive value of high sensitivity C-reactive protein in three-vessel disease patients with and without type 2 diabetes. Cardiovasc Diabetol 2023 Apr 20; 22(1): 91;","DOI":"10.1186\/s12933-023-01830-7"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, et al. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003 Nov; 26(11): 3160-7;","DOI":"10.2337\/diacare.26.11.3160"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Chen S, Shen Y, Liu YH , Dai Y, Wu ZM, Wang XQ , et al. Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 2021 Mar 13; 20(1): 64;","DOI":"10.1186\/s12933-021-01257-y"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Klen J, Gori\u010dar K, Dol\u017ean V The associations of PON1 and APOE polymorphisms with plasma lipid levels and the risk for late complications in type 2 diabetes patients. J Med Biochem 2023; 42 (4): 675-84;","DOI":"10.5937\/jomb0-43154"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Pandey G K, Balasubramanyam J, Balakumar M, Deepa M, Anjana RM, Abhijit S, et al. Altered circulating levels of retinol binding protein 4 and transthyretin in relation to insulin resistance, obesity, and glucose intolerance in Asian Indians. Endocr Pract 2015 Aug; 21(8): 861-9;","DOI":"10.4158\/EP14558.OR"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Chen ZZ , Gerszten RE. Metabolomics and Proteomics in Type 2 Diabetes. Circ Res 2020 May 22; 126(11): 1613-27;","DOI":"10.1161\/CIRCRESAHA.120.315898"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Munkhtulga L, Nagashima S, Nakayama K, Utsumi N, Yanagisawa Y, Gotoh T, et al. Regulatory SNP in the RBP4 gene modified the expression in adipocytes and associated with BMI. Obesity (Silver Spring) 2010 May; 18(5): 1006-14;","DOI":"10.1038\/oby.2009.358"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Fan J, Hu J. Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic b-cell function. Endocrine 2024 Sep; 85(3): 1020-34;","DOI":"10.1007\/s12020-024-03777-5"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Huang, Ya-Li, Ysn-Lin Chen, Jiunn-Diann Lin, Dee Pei, Pietro Pitrone, Jin-Shuen Chen, et al. Visfatin and Retinol Binding Protein-4 in Young-Onset Type 2 Diabetes Mellitus. Medicina 2023; 59(7): 1278;","DOI":"10.3390\/medicina59071278"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Nono Nankam PA, Bl\u00fcher M. Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol 2021 Jul 1; 531: 111312;","DOI":"10.1016\/j.mce.2021.111312"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Al-Absi B, Al-Habori M, Saif-Ali R. Plasma Lipocalin-2 and Adiponectin are Affected by Obesity Rather Than Type 2 Diabetes Mellitus per se. Diabetes Metab Syndr Obes 2021 Nov 16; 14: 4547-56;","DOI":"10.2147\/DMSO.S338254"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Mahfouz MH, Assiri AM, Mukhtar MH. Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy. Biomark Insights 2016 Feb 16; 11: 31-40;","DOI":"10.4137\/BMI.S33191"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Akbay E, Muslu N, Nayir E, Ozhan O, Kiykim A. Serum retinol binding protein 4 level is related with renal functions in Type 2 diabetes. J Endocrinol Invest 2010 Nov; 33(10): 725-9;","DOI":"10.1007\/BF03346678"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Park H., Green M. H., Shaffer M. L. Association between serum retinol-binding protein 4 concentrations and clinical indices in subjects with type 2 diabetes: a meta-analysis. Journal of Human Nutrition and Dietetics 2012; 25(4): 300-10;","DOI":"10.1111\/j.1365-277X.2012.01262.x"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Li JY, Chen X X , Lu XH , Zhang CB, Shi QP Feng L. Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes. Biosci Rep 2018 Sep 12; 38(5): BSR20181100;","DOI":"10.1042\/BSR20181100"}],"container-title":["Journal of Medical Biochemistry"],"original-title":["Uloga inflamatornih biomarkera RBP4, lipokalina-2 i hsCRP-a u predijabetesu i kod dijabetesa tipa 2"],"language":"en","link":[{"URL":"https:\/\/scindeks-clanci.ceon.rs\/data\/pdf\/1452-8258\/2025\/1452-82582505067O.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T13:53:44Z","timestamp":1755784424000},"score":1,"resource":{"primary":{"URL":"https:\/\/scindeks.ceon.rs\/Article.aspx?artid=1452-82582505067O"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.5937\/jomb0-57001","relation":{},"ISSN":["1452-8258","1452-8266"],"issn-type":[{"value":"1452-8258","type":"print"},{"value":"1452-8266","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]}}}