{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:41:56Z","timestamp":1776235316043,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association between insulin administration and 28-day mortality in non-diabetic patients with sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis of 11,289 critically ill patients with sepsis in the MIMIC-IV database was conducted. Propensity score matching (PSM) was employed to balance baseline characteristics between the insulin-treated and untreated cohorts. The primary outcome was 28-day mortality; secondary outcome measures included intensive care unit (ICU) and hospital length of stay (LOS). The association between insulin use and mortality was evaluated via Cox regression analysis, and survival was estimated using Kaplan-Meier curves and log-rank tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 11,289 non-diabetic patients meeting the inclusion criteria, 1,172 (10.4%) received insulin. After PSM, the final analysis included 2,960 patients (782 in the insulin group and 2,178 in the control group). Baseline characteristics were well-balanced, with standardized mean differences (SMDs) close to zero. Insulin use was significantly associated with a reduced 28-day mortality rate (hazard ratio [HR] 0.63-0.67, p &amp;lt; 0.001), a finding that remained consistent across all subgroups. However, patients receiving insulin therapy had a longer median ICU LOS (5 days vs. 4 days, p &amp;lt; 0.001) and a more extended hospital LOS (12 days vs. 10 days, p &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Insulin therapy may improve the survival rate among non-diabetic patients with sepsis but does not shorten the duration of hospitalization. Further research is warranted to elucidate the underlying mechanism and validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1806847","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:41:48Z","timestamp":1776231708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of insulin on 28-day mortality in non-diabetic sepsis patients: a retrospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Yifei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, Hubei, China"]},{"name":"The Institute of Geriatric Anesthesia, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, Hubei, China"]},{"name":"The Institute of Geriatric Anesthesia, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, Hubei, China"]},{"name":"The Institute of Geriatric Anesthesia, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, Hubei, China"]},{"name":"The Institute of Geriatric Anesthesia, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangdong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi\u2019an Jiao tong University","place":["Xi\u2019an, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Yichang Central People\u2019s Hospital","place":["Yichang, Hubei, China"]},{"name":"The Institute of Geriatric Anesthesia, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1189\/jlb.0503195","article-title":"The roles of insulin and hyperglycemia in sepsis pathogenesis","volume":"75","author":"Andersen","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.eprac.2021.01.018","article-title":"Guideline-concordant insulin infusion initiation among critically ill patients with sepsis","volume":"27","author":"Bosch","year":"2021","journal-title":"Endocr Pract."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583385","article-title":"Insulin modulates inflammatory cytokine release in acute stages and augments expression of adhesion molecules and leukocytes in lungs on chronic stages of paracoccidioidomycosis","volume":"11","author":"Casagrande","year":"2020","journal-title":"Front. Immunol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.587229","article-title":"Insulin reduces inflammation by regulating the activation of the NLRP3 inflammasome","volume":"11","author":"Chang","year":"2021","journal-title":"Front. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine storm and sepsis disease pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103372","article-title":"Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles","volume":"77","author":"Clemen","year":"2024","journal-title":"Redox Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1159\/000534074","article-title":"Metabolism and nutrition in sepsis: in need of a paradigm shift","volume":"147","author":"Collins","year":"2023","journal-title":"Nephron Clin. Pract."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s00592-021-01728-4","article-title":"Type 2 diabetes mellitus and sepsis: state of the art, certainties and missing evidence","volume":"58","author":"Costantini","year":"2021","journal-title":"Acta Diabetol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1056\/NEJMoa0810625","article-title":"Intensive versus conventional glucose control in critically ill patients","volume":"360","author":"Finfer","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1577105","article-title":"Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy","volume":"16","author":"Gao","year":"2025","journal-title":"Front. Immunol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215376","article-title":"The pathogenesis of sepsis and potential therapeutic targets","volume":"20","author":"Huang","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"158","DOI":"10.2337\/diaclin.34.3.158","article-title":"Extreme insulin resistance in critically ill patient with sepsis","volume":"34","author":"Illuri","year":"2016","journal-title":"Clin. Diabetes: A Publ. Am. Diabetes Assoc."},{"key":"B14","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/21548331.2015.1066227","article-title":"Glycemic control in the critically ill: what have we learned since NICE-SUGAR","volume":"43","author":"Krinsley","year":"2015","journal-title":"Hosp. Pract. 1995"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1007\/s15010-024-02264-3","article-title":"Association of stress hyperglycemia ratio and mortality in patients with sepsis: results from 13,199 patients","volume":"52","author":"Li","year":"2024","journal-title":"Infection"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146549","article-title":"Lower initial insulin-like growth factor-binding protein-3 concentrations may reflect immune suppression and predict increased risk of sepsis-related mortality","volume":"26","author":"Mearelli","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s10020-025-01074-z","article-title":"Endocrine and metabolic alterations in response to systemic inflammation and sepsis: a review article","volume":"31","author":"Mehdi","year":"2025","journal-title":"Mol. Med. Cambridge Mass"},{"key":"B18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jcrc.2017.04.015","article-title":"Sepsis and septic shock: pathogenesis and treatment perspectives","volume":"40","author":"Minasyan","year":"2017","journal-title":"J. Crit. Care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1097\/MNH.0000000000000801","article-title":"When a calorie isn\u2019t just a calorie: a revised look at nutrition in critically ill patients with sepsis and acute kidney injury","volume":"31","author":"Nadamuni","year":"2022","journal-title":"Curr. Opin. Nephrol Hypertens."},{"key":"B20","doi-asserted-by":"publisher","first-page":"65","DOI":"10.4266\/acc.2018.00157","article-title":"Role of mitochondrial oxidative stress in sepsis","volume":"33","author":"Nagar","year":"2018","journal-title":"Acute Crit. Care"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10173798","article-title":"Targeting oxidative stress in septic acute kidney injury: from theory to practice","volume":"10","author":"Ow","year":"2021","journal-title":"J. Clin. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"131","DOI":"10.14715\/cmb\/2020.66.5.23","article-title":"LncRNA MEG3 expression in sepsis and its effect on LPS-induced macrophage function","volume":"66","author":"Pan","year":"2020","journal-title":"Cell. Mol. Biol. Noisy-Le-Grand France"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/biology12111432","article-title":"The role of the insulin\/glucose ratio in the regulation of pathogen biofilm formation","volume":"12","author":"Plotkin","year":"2023","journal-title":"Biol. Bsl"},{"key":"B24","doi-asserted-by":"publisher","first-page":"53","DOI":"10.5152\/eurasianjmed.2017.17062","article-title":"Sepsis and septic shock: current treatment strategies and new approaches","volume":"49","author":"Polat","year":"2017","journal-title":"Eur J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.burns.2016.09.023","article-title":"Oxidative stress in sepsis: pathophysiological implications justifying antioxidant co-therapy","volume":"43","author":"Prauchner","year":"2017","journal-title":"Burn: J. Int. Soc. For. Burn Inj"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn9285","article-title":"An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis","volume":"16","author":"Rahmel","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1007\/s12325-017-0622-8","article-title":"Sepsis: a review of advances in management","volume":"34","author":"Rello","year":"2017","journal-title":"Adv. Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"B29","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.amjms.2020.11.007","article-title":"Hyperglycemia, insulin, and insulin resistance in sepsis","volume":"361","author":"Rivas","year":"2021","journal-title":"Am. J. Med. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"771","DOI":"10.2337\/dc10-1185","article-title":"Diabetes and sepsis: preclinical findings and clinical relevance","volume":"34","author":"Schuetz","year":"2011","journal-title":"Diabetes Care"},{"key":"B31","doi-asserted-by":"publisher","first-page":"801","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":"B32","doi-asserted-by":"publisher","first-page":"2450","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":"B33","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/S0140-6736(04)17665-4","article-title":"Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients","volume":"365","author":"Vanhorebeek","year":"2005","journal-title":"Lancet Lond Engl"},{"key":"B34","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S2213-8587(25)00295-5","article-title":"Prediabetes remission and cardiovascular morbidity and mortality: post-hoc analyses from the Diabetes Prevention Program Outcome study and the DaQing Diabetes Prevention Outcome study","volume":"14","author":"Vazquez Arreola","year":"2026","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.722004","article-title":"Long non-coding RNAs as biomarkers and therapeutic targets in sepsis","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3546","DOI":"10.12659\/msm.903144","article-title":"Association between diabetes mellitus and outcomes of patients with sepsis: a meta-analysis","volume":"23","author":"Wang","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"B37","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.hrtlng.2021.07.017","article-title":"Hypoglycemia and mortality in sepsis patients: a systematic review and meta-analysis","volume":"50","author":"Wang","year":"2021","journal-title":"Heart Lung: J. Crit. Care"},{"key":"B38","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1177\/0148607187011004345","article-title":"Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique","volume":"11","author":"White","year":"1987","journal-title":"JPEN J. Parenter Enteral Nutr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s11658-025-00784-w","article-title":"Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis","volume":"30","author":"Wu","year":"2025","journal-title":"Cell. Mol. Biol. Lett."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.706908","article-title":"GLP-1 receptor: a new target for sepsis","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1186\/s40001-024-02129-3","article-title":"Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP\/HIF-1\u03b1 pathway","volume":"29","author":"Yao","year":"2024","journal-title":"Eur. J. Med. Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1806847\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:41:49Z","timestamp":1776231709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1806847\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":41,"alternative-id":["10.3389\/fcimb.2026.1806847"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1806847","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1806847"}}