{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:52:52Z","timestamp":1794009172582,"version":"4.8.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Blood glucose (BG) dysregulation, including hyperglycemia, hypoglycemia and increased glycemic variability (GV), is common in septic patients and potentially associated with poor clinical outcomes. However, the prognostic value of early BG trajectories remains unclear. We intend to investigate the association between the early dynamic trajectory of BG and 1-year mortality among sepsis patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study comprises a derivation cohort of sepsis patients admitted to the First Affiliated Hospital of Sun Yat-sen University (FAH-SYSU) from January 2018 to December 2023, and an external validation cohort of 10,874 sepsis patients from the Medical Information Mart for Intensive Care (MIMIC) IV database. Distinct clusters were demarcated using K-means clustering based on the BG trajectory within the first 48 hours after ICU admission, while the optimal number of clusters was determined by a consensus of quantitative metrics and the elbow plot. Kaplan-Meier survival curves and multivariable Cox proportional hazards regression models were used to assess the association between these identified clusters and 1-year mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 3,655 sepsis patients from the FAH-SYSU dataset, we identified 5 distinct clusters of BG trajectories, which were significantly associated with 1-year mortality risk. In the full Cox regression model, patients with \u201clow-stable\u201d and \u201cmoderate-stable\u201d trajectories had the lowest 1-year mortality risk (<jats:italic>P<\/jats:italic> = 0.077). Conversely, patients with a \u201chigh-stable\u201d trajectory (HR: 1.61, 95% CI: 1.35-1.92, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) and those exhibiting unstable trends had significantly higher mortality risks (\u201chigh-decreasing\u201d, HR: 1.38, 95% CI: 1.16-1.65, <jats:italic>P<\/jats:italic> &amp;lt; 0.001; \u201cmoderate-increasing\u201d, HR: 1.37, 95% CI: 1.18-1.60, <jats:italic>P<\/jats:italic> &amp;lt; 0.001). External validation found consistent clusters with similar mortality trends. Restricted cubic spline analysis demonstrated a U-shaped association for mean glucose levels and a J-shaped relationship for GV linked to 1-year mortality risks, while an optimal glycemic range of 122 to 160 mg\/dL and GV less than 0.18 indicated improved survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Early BG trajectory patterns are independently associated with long-term mortality in sepsis patients. Incorporating dynamic BG measurements into clinical practice may improve risk stratification and guide individualized glucose management strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1610519","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:29:19Z","timestamp":1749101359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Identifying early blood glucose trajectories in sepsis linked to distinct long-term outcomes: a K-means clustering study with external validation"],"prefix":"10.3389","volume":"16","author":[{"given":"Huan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayan","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxu","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Yin","family":"Lui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The immunology of sepsis","volume":"54","author":"van der Poll","year":"2021","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.17.2167","article-title":"Hyperglycemia in acutely ill patients","volume":"288","author":"Montori","year":"2002","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: a unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60553-5","article-title":"Stress hyperglycaemia","volume":"373","author":"Dungan","year":"2009","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1164\/rccm.202309-1696SO","article-title":"Our scientific journey through the ups and downs of blood glucose control in the ICU","volume":"209","author":"Van den Berghe","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000109698.70638.2B","article-title":"Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma","volume":"109","author":"Khatri","year":"2004","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.43447","article-title":"Is intensive glucose control bad for critically ill patients? 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