{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:40:28Z","timestamp":1792392028336,"version":"4.4.0"},"reference-count":85,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Diabetic polyneuropathy (DPN) is a debilitating complication of diabetes that affects motor nerves and may impair skeletal muscle health. This study investigated skeletal muscle proteomic alterations associated with DPN compared with type 2 diabetes without DPN (T2D) and healthy controls (CON).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Design<\/jats:title>\n                    <jats:p>An exploratory proteomic profiling was performed in 15 participants divided into three groups based on clinical and neurophysiological diagnosis (DPN, n\u00a0=\u00a05; T2D, n\u00a0=\u00a05; CON, n\u00a0=\u00a05). Biopsies from the gastrocnemius lateralis muscle were analyzed using LC\u2010MS\/MS\u2013based proteomics and pathway enrichment analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 265 and 444 proteins were differentially expressed in DPN compared with T2D and CON, respectively (q &lt; 0.05). Enrichment analyses revealed marked alterations in mitochondrial\u2010related pathways, including cellular respiration, distinguishing DPN from both comparison groups. Differences between T2D and CON were present but less pronounced. DPN was characterized by downregulation of glycogen\u2010regulating proteins (phosphorylase kinase G1 and A1) and upregulation of ferritin light chain (FTL), alpha actin 2, and myosin\u2010binding protein H.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical relevance<\/jats:title>\n                    <jats:p>DPN is associated with a distinct and progressive skeletal muscle proteomic phenotype, supporting mitochondrial dysfunction as a key feature and providing a basis for future mechanistic and therapeutic studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/prca.70060","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:47:11Z","timestamp":1792388831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetic Polyneuropathy Patients Exhibit an Altered Skeletal Muscle Proteome Phenotype"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4877-3593","authenticated-orcid":false,"given":"Frederik Forsberg","family":"Thybo","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"Steno Diabetes Center Aarhus Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina Snopek","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1818-9860","authenticated-orcid":false,"given":"Jesper Emil","family":"Jakobsgaard","sequence":"additional","affiliation":[{"name":"NMD Pharma A\/S  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Neurology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5810-5241","authenticated-orcid":false,"given":"Kristian","family":"Vissing","sequence":"additional","affiliation":[{"name":"Exercise Biology Department of Public Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5585-639X","authenticated-orcid":false,"given":"Johan","family":"Palmfeldt","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223\u2010014\u20109915\u2010y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.05.005"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029793"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.49"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12238"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114857"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/84.3.475"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.012"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u2010185X.2010.00161.x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1462"},{"issue":"1","key":"e_1_2_12_12_1","first-page":"S62","article-title":"Diagnosis and Classification of Diabetes Mellitus","volume":"34","author":"Diabetes A.","year":"2011","journal-title":"Diabetes Care"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","DOI":"10.1002\/9781118387658","volume-title":"International Textbook of Diabetes Mellitus","author":"DeFronzo R. A.","year":"2015"},{"key":"e_1_2_12_14_1","volume-title":"IDF DIABETES ATLAS","author":"Magliano D. J.","year":"2021"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.29.3.116"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.4.817"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20102042"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70065\u20100"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100092\u20101"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296821997921"},{"issue":"3","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.diabet.2008.11.004","article-title":"Prevalence and Impact on Quality of Life of Peripheral Neuropathy With or Without Neuropathic Pain in Type 1 and Type 2 Diabetic Patients Attending Hospital Outpatients Clinics","volume":"35","author":"Van Acker K.","year":"2009","journal-title":"Diabetes & Metabolism"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010014\u20100473\u20105"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1226"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.12.005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.137"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1071100720907035"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00441.2014"},{"issue":"7","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1007\/s00421-023-05150-2","article-title":"Mechanisms Underlying Altered Neuromuscular Function in People With DPN","volume":"123","author":"Le Corre A.","year":"2023","journal-title":"European Journal of Applied Physiology"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2658"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100763"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010012\u20102456\u2010x"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09\u20100214"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.006650"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010018\u20100154\u20106"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010021\u201005646\u20106"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14470"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.10.035"},{"issue":"9","key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/bioinformatics\/bth078","article-title":"Open Source Clustering Software","volume":"20","author":"Hoon M. J.","year":"2004","journal-title":"Bioinformatics"},{"key":"e_1_2_12_39_1","unstructured":"Morpheus.https:\/\/software.broadinstitute.org\/morpheus."},{"key":"e_1_2_12_40_1","unstructured":"J. D.Storey A. J.Bass A.Dabney andD.Robinson \u201cqvalue: Q\u2010value estimation for false discovery rate control \u201d (2024) http:\/\/github.com\/jdstorey\/qvalue."},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr671"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad960"},{"issue":"1","key":"e_1_2_12_45_1","first-page":"D498","article-title":"The Reactome Pathway Knowledgebase","volume":"48","author":"Jassal B.","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_2_12_47_1","unstructured":"R.Team RStudio: Integrated Development for R [Software]2020RStudio PBC http:\/\/www.rstudio.com."},{"key":"e_1_2_12_48_1","volume-title":"Elegant Graphics for Data Analysis","author":"Wickham H.","year":"2016"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013984"},{"key":"e_1_2_12_51_1","unstructured":"M.Kucera \u201cBaderLab\/AutoAnnotateApp: AutoAnnotate 1.2 (release\/v1.2.0) [Software]. Zenodo \u201d (2017) https:\/\/zenodo.org\/records\/883467."},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00016"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050632\u20102"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010197410000\u201000005"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395\u2010021\u201000279\u20100"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14658"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/pmj.2005.039032"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679\u2010024\u201000561\u20104"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17\u20102062"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.3745"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753\u20100407.12124"},{"issue":"5","key":"e_1_2_12_62_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1152\/japplphysiol.00394.2024","article-title":"Does One Biopsy Cut It? Revisiting Human Muscle Fiber Type Composition Variability Using Repeated Biopsies in the Vastus Lateralis and Gastrocnemius Medialis","volume":"137","author":"Van de Casteele F.","year":"2024","journal-title":"Journal of Applied Physiology (1985)"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13124"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01139.2013"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.2522\/ptj.20080079"},{"issue":"12","key":"e_1_2_12_66_1","doi-asserted-by":"crossref","DOI":"10.1085\/jgp.202413604","article-title":"Functional Role of Myosin\u2010Binding Protein H in Thick Filaments of Developing Vertebrate Fast\u2010Twitch Skeletal Muscle","volume":"156","author":"Mead A. F.","year":"2024","journal-title":"Journal of General Physiology"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00412.2005"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.10.013"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.04.007"},{"key":"e_1_2_12_70_1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/joa.14207","article-title":"Achilles Tenocytes from Diabetic and Non Diabetic Donors Exposed to Hyperglycemia Respond Differentially to Inflammatory Stimuli and Stretch","volume":"248","author":"Fleischmann N.","year":"2024","journal-title":"Journal of Anatomy"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200996"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.11.044"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364\u2010023\u201000515\u20103"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.2337\/db22\u20100056"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.11.042"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/ebm.2024.10280"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534\u2010024\u201000600\u20106"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13008"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.625"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031031"},{"issue":"7","key":"e_1_2_12_81_1","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.3390\/biomedicines12071390","article-title":"Recent Advances in Biomolecular Patho\u2010Mechanistic Pathways Behind the Development and Progression of Diabetic Neuropathy","volume":"12","author":"Ratan Y.","year":"2024","journal-title":"Biomedicines"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107479"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00227.2004"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.008"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1011"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2025.2451704"}],"container-title":["PROTEOMICS \u2013 Clinical Applications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prca.70060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prca.70060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prca.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:47:14Z","timestamp":1792388834000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prca.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,18]]},"references-count":85,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/prca.70060"],"URL":"https:\/\/doi.org\/10.1002\/prca.70060","archive":["Portico"],"relation":{},"ISSN":["1862-8346","1862-8354"],"issn-type":[{"value":"1862-8346","type":"print"},{"value":"1862-8354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,18]]},"assertion":[{"value":"2026-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70060"}}