{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:15:42Z","timestamp":1788534942305,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570128"],"award-info":[{"award-number":["82570128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is a highly heterogeneous disease characterised by subtypes with variations in aetiology, disease progression, and risk of complications. However, potential drug targets for these subtypes have not been explored. This study aims to investigate potential drug targets by integrating proteomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Summary\u2010level data of circulating proteins were extracted from the UK Biobank and the deCODE Health Study. Genetic associations with five diabetes subtypes were obtained from Swedish All New Diabetics in Scania and Malm\u00f6 Diet and Cancer cohort, including severe autoimmune diabetes (SAID), severe insulin\u2010deficient diabetes (SIDD), severe insulin\u2010resistant diabetes (SIRD), mild obesity\u2010related diabetes (MOD), and mild age\u2010related diabetes (MARD). The associations between circulating proteins and diabetes subtypes were assessed through Mendelian randomisation, followed by multiple sensitivity and colocalization analyses. Additionally, tissue\u2010specific, pathway and functional enrichment analysis, assessment of protein druggability, and the protein\u2013protein interaction (PPI) networks were used to further explore biological mechanisms and therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetically predicted levels of 2, 2, 9, 3, and 5 circulating proteins were associated with SIRD, SIDD, MARD, MOD, and SAID, respectively. Colocalization analyses further revealed links between GRN with MARD\/SIRD, LILRB5 with SIDD\/MARD, CR1 with MARD, TNFSF12 with MOD, and DAPK2 with SAID. Enrichment analysis suggested that these proteins were mainly enriched in blood and adipose tissues and involved in immune and inflammatory related pathways. PPI analysis revealed GRN, TNFSF12, and DAPK2 are associated with known T2D targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identified several potential drug targets for different subtypes of diabetes using an integrated genetic approach, yielding new insights for precision medicine of diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70088","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T09:59:32Z","timestamp":1756720772000},"page":"6894-6904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrative proteomic analysis provides novel therapeutic insights for etiological subtypes of diabetes"],"prefix":"10.1111","volume":"27","author":[{"given":"Jiahe","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-6991","authenticated-orcid":false,"given":"Ningjian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit Mohan","family":"Anjana","sequence":"additional","affiliation":[{"name":"Madras Diabetes Research Foundation (ICMR \u2013 Collaborating Centre of Excellence and Dr. Mohan's Diabetes Specialities Centre (IDF Centre of Excellence in Diabetes Care)  Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr V.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Division of Functional Pharmacology and Neuroscience Uppsala University  Uppsala 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