{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:35:59Z","timestamp":1793126159344,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"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":["92253304"],"award-info":[{"award-number":["92253304"]}],"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Prediabetes is biologically heterogeneous, but molecular subtypes linked to diabetes progression remain poorly defined. We aimed to identify plasma proteome\u2010based subtypes of impaired fasting glucose (IFG), characterise their molecular features and assess their association with future diabetes risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We quantified 2584 plasma proteins using liquid chromatography\u2010mass spectrometry in 538 IFG participants from a prospective discovery cohort (Nutrition and Health of Aging Population in China, NHAPC). Proteomic subtypes were defined by consensus clustering, linked to longitudinal changes in insulin sensitivity and incident type 2 diabetes mellitus (T2DM), which were further validated in an independent Shanghai Brain Aging Study (SBAS) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two reproducible IFG molecular subtypes based on plasma proteomics were identified. The high\u2010risk subtype showed higher incident diabetes and a greater 6\u2010year decline in insulin sensitivity and was characterised by enrichment of glycolysis\/gluconeogenesis, insulin signalling and neutrophil degranulation, together with a dyslipidemic lipidomic profile indicating co\u2010dysregulation of glucose and lipid homeostasis. The low\u2010risk subtype demonstrated a higher complement cascade and high\u2010density lipoprotein particle remodelling signature. In the high\u2010risk subtype, key proteins and lipids showed stronger associations with longitudinal declines in insulin sensitivity, including PPBP, PGK1 and ALDOA, as well as PE\u2010P 18:0\/20:3 and PE\u2010P 18:1\/20:3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Proteome\u2010based molecular subtyping stratifies IFG individuals with similar fasting glucose levels but distinct biology and future diabetes risk, supporting earlier and more targeted prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70962","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:02:03Z","timestamp":1780635723000},"page":"7483-7493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Signature of Prediabetes With High\u2010Risk of Diabetes Revealed by Deep Plasma Proteome"],"prefix":"10.1111","volume":"28","author":[{"given":"Yuanyuan","family":"Yin","sequence":"first","affiliation":[{"name":"Joint Lab of Shanghai Clinical Research and Trial Center Affiliated to ShanghaiTech University &amp; National Facility for Protein\u00a0Science in Shanghai Affiliated to Shanghai Advanced Research Institute, Chinese Academy of Sciences  Shanghai China"},{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai China"},{"name":"Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Gao","sequence":"additional","affiliation":[{"name":"Joint Lab of Shanghai Clinical Research and Trial Center Affiliated to ShanghaiTech University &amp; National Facility for Protein\u00a0Science in Shanghai Affiliated to Shanghai Advanced Research Institute, Chinese Academy of Sciences  Shanghai 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