{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:38:20Z","timestamp":1768221500565,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean Government","doi-asserted-by":"publisher","award":["NRF-2022R1A2C1011069"],"award-info":[{"award-number":["NRF-2022R1A2C1011069"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"the Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["HR18C001204"],"award-info":[{"award-number":["HR18C001204"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes mellitus (T2D) that reduces quality of life and increases the risk of foot ulcers and amputations. Early detection is essential, and blood-based biomarkers may support improved screening and timely intervention. This study aimed to identify novel circulating biomarkers for the identification of DPN in patients with T2D. Methods: In the screening phase, plasma samples from 43 participants (10 healthy volunteers [HV], 20 T2D without complications, and 13 T2D with DPN) were analyzed using an antibody array targeting 310 proteins. Thirteen differentially expressed proteins were identified, and six hub proteins were selected through bioinformatic analysis. In the validation phase, plasma concentrations of the six proteins were measured by ELISA in 252 subjects (100 HV, 97 T2D without complications, and 55 T2D with DPN). Mucin-1 expression in sciatic nerves was further evaluated in db\/db mice. Results: Of the six hub proteins (TGFB1, MUC1, PF4, IL2RA, SELL, B2M), only mucin-1 showed a significant increase in the DPN group. Plasma mucin-1 positively correlated with MNSI scores and negatively with motor and sensory nerve conduction velocities. In db\/db mice, sciatic nerve mucin-1 expression was elevated, while CD31 expression was reduced. Conclusions: Plasma mucin-1 is strongly associated with DPN in both humans and animals and may serve as a promising biomarker for the screening and early identification of DPN.<\/jats:p>","DOI":"10.3390\/biom16010128","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Mucin-1 as a Potential Biomarker for Diabetic Peripheral Neuropathy in Type 2 Diabetes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-5977","authenticated-orcid":false,"given":"Jae-Hyung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Nhi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Min","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-3977","authenticated-orcid":false,"given":"Gyeong Im","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junho","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Research, Keimyung University Dongsan Medical Center, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-4329","authenticated-orcid":false,"given":"Eun Yeong","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-7728","authenticated-orcid":false,"given":"Hochan","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhu, J., Hu, Z., Luo, Y., Liu, Y., Luo, W., Du, X., Luo, Z., Hu, J., and Peng, S. (2023). Diabetic peripheral neuropathy: Pathogenetic mechanisms and treatment. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1265372"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.2040-1124.2010.00070.x","article-title":"Mechanism of diabetic neuropathy: Where are we now and where to go?","volume":"2","author":"Yagihashi","year":"2011","journal-title":"J. Diabetes Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41392-025-02175-1","article-title":"Diabetic neuropathy: Cutting-edge research and future directions","volume":"10","author":"Yang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhou, P., Zhou, J.S., Li, J.J., Qin, L., Hu, W.F., Zhang, X.Y., Wang, J.X., and Shi, Z. (2025). Prevalence and risk factors for painful diabetic peripheral neuropathy: A systematic review and meta-analysis. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1564867"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S1474-4422(12)70065-0","article-title":"Diabetic neuropathy: Clinical manifestations and current treatments","volume":"11","author":"Callaghan","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S2213-8587(19)30081-6","article-title":"Diabetic peripheral neuropathy: Advances in diagnosis and strategies for screening and early intervention","volume":"7","author":"Selvarajah","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3803\/EnM.2016.31.2.230","article-title":"Recent Advances in Diagnostic Strategies for Diabetic Peripheral Neuropathy","volume":"31","author":"Won","year":"2016","journal-title":"Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5902036","DOI":"10.1155\/jdr\/5902036","article-title":"Diagnostic Accuracy of Screening Tests for Diabetic Peripheral Neuropathy: An Umbrella Review","volume":"2024","author":"Mogilevskaya","year":"2024","journal-title":"J. Diabetes Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Burgess, J., Frank, B., Marshall, A., Khalil, R.S., Ponirakis, G., Petropoulos, I.N., Cuthbertson, D.J., Malik, R.A., and Alam, U. (2021). Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020165"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2248593","DOI":"10.1001\/jamanetworkopen.2022.48593","article-title":"Types and Concentrations of Blood-Based Biomarkers in Adults with Peripheral Neuropathies: A Systematic Review and Meta-analysis","volume":"5","author":"Fundaun","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/ane.13650","article-title":"Blood biomarkers of peripheral neuropathy","volume":"146","author":"Rossor","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4093\/dmj.2025.0299","article-title":"Clinical Phenotypes of Diabetic Peripheral Neuropathy: Implications for Phenotypic-Based Therapeutics Strategies","volume":"49","author":"Lee","year":"2025","journal-title":"Diabetes Metab. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF00294509","article-title":"Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes","volume":"88","author":"Weis","year":"1994","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jns.2003.09.011","article-title":"Perineurial cell basement membrane thickening and myelinated nerve fibre loss in diabetic and nondiabetic peripheral nerve","volume":"217","author":"Hill","year":"2004","journal-title":"J. Neurol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1007\/s00018-015-2014-z","article-title":"MUC1 (CD227): A multi-tasked molecule","volume":"72","author":"Apostolopoulos","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_16","first-page":"bio036830","article-title":"Characterization of diabetic neuropathy progression in a mouse model of type 2 diabetes mellitus","volume":"7","author":"Contador","year":"2018","journal-title":"Biol. Open"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care, 48, S27\u2013S49.","DOI":"10.2337\/dc25-S002"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3803\/EnM.2021.962","article-title":"Association of Protein Z with Prediabetes and Type 2 Diabetes","volume":"36","author":"Bae","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0344-0338(11)80727-2","article-title":"The use of CD31 and collagen IV as vascular markers. A study of 56 vascular lesions","volume":"191","author":"Schmidt","year":"1995","journal-title":"Pathol. Res. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S1474-4422(22)00188-0","article-title":"Towards prevention of diabetic peripheral neuropathy: Clinical presentation, pathogenesis, and new treatments","volume":"21","author":"Elafros","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100649","DOI":"10.1016\/j.eclinm.2020.100649","article-title":"Proinflammatory cytokines predict the incidence of diabetic peripheral neuropathy over 5 years in Chinese type 2 diabetes patients: A prospective cohort study","volume":"31","author":"Zheng","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Oshitari, T. (2023). Advanced Glycation End-Products and Diabetic Neuropathy of the Retina. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032927"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tejchman, K., Kotfis, K., and Sienko, J. (2021). Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158010"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5943","DOI":"10.12659\/MSM.909449","article-title":"Diagnostic Significance of Serum Levels of Nerve Growth Factor and Brain Derived Neurotrophic Factor in Diabetic Peripheral Neuropathy","volume":"24","author":"Sun","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15365","DOI":"10.4238\/2015.November.30.14","article-title":"Elevated serum homocysteine level in the development of diabetic peripheral neuropathy","volume":"14","author":"Zheng","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lv, N., Jia, L., Liu, F., Cheng, L., Liu, F., Kuang, J., and Chen, X. (2024). Elevated circulating homocysteine concentrations delayed nerve conduction velocity and increase the risk of diabetic kidney disease in patients with type 2 diabetes. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1451758"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00125-022-05846-8","article-title":"Serum neurofilament light chain: A novel biomarker for early diabetic sensorimotor polyneuropathy","volume":"66","author":"Maalmi","year":"2023","journal-title":"Diabetologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/BF00389494","article-title":"A comparison of perineurial and vascular basal laminal changes in diabetic neuropathy","volume":"88","author":"Bradley","year":"1994","journal-title":"Acta Neuropathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1365-2990.1989.tb01234.x","article-title":"Diabetic neuropathy: Abnormalities of Schwann cell and perineurial basal laminae. Implications for diabetic vasculopathy","volume":"15","author":"King","year":"1989","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70025","DOI":"10.1111\/jon.70025","article-title":"High-Field Diffusion Tensor Imaging of Median, Tibial, and Sural Nerves in Type 2 Diabetes With Morphometric Analysis","volume":"35","author":"Pusnik","year":"2025","journal-title":"J. Neuroimaging"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Evans, M.C., Wade, C., Hohenschurz-Schmidt, D., Lally, P., Ugwudike, A., Shah, K., Bangerter, N., Sharp, D.J., and Rice, A.S.C. (2021). Magnetic Resonance Imaging as a Biomarker in Diabetic and HIV-Associated Peripheral Neuropathy: A Systematic Review-Based Narrative. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.727311"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20220336","DOI":"10.1259\/bjr.20220336","article-title":"Sural nerve: Imaging anatomy and pathology","volume":"96","author":"Jackson","year":"2023","journal-title":"Br. J. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1007\/s00125-023-06009-z","article-title":"Structural changes in Schwann cells and nerve fibres in type 1 diabetes: Relationship with diabetic polyneuropathy","volume":"66","author":"Hu","year":"2023","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/(SICI)1097-4598(199606)19:6<722::AID-MUS6>3.0.CO;2-C","article-title":"Diabetic peripheral neuropathy: A clinicopathologic and immunohistochemical analysis of sural nerve biopsies","volume":"19","author":"Younger","year":"1996","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/mi.2012.98","article-title":"MUC1 and MUC13 differentially regulate epithelial inflammation in response to inflammatory and infectious stimuli","volume":"6","author":"Sheng","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45721","DOI":"10.1074\/jbc.M408027200","article-title":"MUC1 oncoprotein activates the FOXO3a transcription factor in a survival response to oxidative stress","volume":"279","author":"Yin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.cca.2010.08.039","article-title":"CA 15-3: Uses and limitation as a biomarker for breast cancer","volume":"411","author":"Duffy","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00432-025-06271-1","article-title":"The assessment of breast cancer biomarkers in diagnosis, prognosis and treatment monitoring: Integrated analysis","volume":"151","author":"Englisz","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0304-3835(96)04473-4","article-title":"Clinical evaluation of potential usefulness of CEA, CA 15-3, and MCA in follow-up of breast cancer patients","volume":"110","author":"Jezersek","year":"1996","journal-title":"Cancer Lett."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:40:24Z","timestamp":1768210824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010128"],"URL":"https:\/\/doi.org\/10.3390\/biom16010128","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}