{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:27:33Z","timestamp":1791498453110,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There was considerable debate regarding the effect of mean blood glucose (MBG) and glycemic variability (GV) on the mortality of septic patients. This retrospective cohort study aimed to assess the association between MBG and GV with ICU mortality of sepsis patients and to explore the optimal MBG range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sepsis patients were enrolled from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). MBG and glycemic coefficient of variation (Glu\n                      <jats:sub>CV<\/jats:sub>\n                      ) were, respectively, calculated to represent the overall glycemic status and GV during ICU stay. The associations between MBG, Glu\n                      <jats:sub>CV<\/jats:sub>\n                      , and ICU mortality of the septic patients were assessed by using multivariate logistic regression in different subgroups and the severity of sepsis. Restricted cubic splines evaluated the optimal MBG target.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 7,104 adult sepsis patients were included. The multivariate logistic regression results showed that increased MBG and Glu\n                      <jats:sub>CV<\/jats:sub>\n                      were significantly correlated with ICU mortality. The adjusted odds ratios were 1.14 (95% CI 1.09\u20131.20) and 1.05 (95% CI 1.00\u20131.12). However, there was no association between hyperglycemia and ICU mortality among diabetes, liver disease, immunosuppression, and hypoglycemia patients. And the impact of high Glu\n                      <jats:sub>CV<\/jats:sub>\n                      on ICU mortality was not observed in those with diabetes, immunosuppression, liver disease, and non-septic shock. The ICU mortality risk of severe hyperglycemia (\u2267200 mg\/dl) and high Glu\n                      <jats:sub>CV<\/jats:sub>\n                      (&amp;gt;31.429%), respectively, elevated 2.30, 3.15, 3.06, and 2.37, 2.79, 3.14-folds in mild (SOFA \u2266 3), middle (SOFA 3\u20137), and severe group (SOFA \u2267 7). The MBG level was associated with the lowest risk of ICU mortality and hypoglycemia between 120 and 140 mg\/dl in the subgroup without diabetes. For the diabetic subset, the incidence of hypoglycemia was significantly reduced when the MBG was 140\u2013190 mg\/dl, but a glycemic control target effectively reducing ICU mortality was not observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      MBG and Glu\n                      <jats:sub>CV<\/jats:sub>\n                      during the ICU stay were associated with all-cause ICU mortality in sepsis patients; however, their harms are not apparent in some particular subgroups. The impact of hyperglycemia and high GV on death increased with the severity of sepsis. The risk of ICU mortality and hypoglycemia in those with no pre-existing diabetes was lower when maintaining the MBG in the range of 120\u2013140 mg\/dl.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2022.857368","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T02:35:25Z","timestamp":1651199725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":115,"title":["Association of Blood Glucose Level and Glycemic Variability With Mortality in Sepsis Patients During ICU Hospitalization"],"prefix":"10.3389","volume":"10","author":[{"given":"Zongqing","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfeng","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1181","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":"B2","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s00134-020-06151-x","article-title":"Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis","volume":"46","author":"Fleischmann-Struzek","year":"2020","journal-title":"Intensive Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1056\/NEJMc060566","article-title":"Intensive insulin therapy in the medical ICU","volume":"354","author":"Tamler","year":"2006","journal-title":"N Engl J Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11892-018-0988-2","article-title":"Critical care management of stress-induced hyperglycemia","volume":"18","author":"Vanhorebeek","year":"2018","journal-title":"Curr Diab Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1097\/CCM.0b013e318283d124","article-title":"Stress hyperglycemia: an essential survival response! Crit Care Med.","volume":"41","author":"Marik","year":"2013"},{"key":"B6","doi-asserted-by":"publisher","first-page":"200","DOI":"10.4161\/viru.25855","article-title":"Clinical controversies in the management of critically ill patients with severe sepsis: resuscitation fluids and glucose control","volume":"5","author":"Finfer","year":"2014","journal-title":"Virulence."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1007\/s11739-021-02693-0","article-title":"Admission hyperglycemia and all-cause mortality in diabetic and non-diabetic patients with acute myocardial infarction: a tertiary center analysis","volume":"16","author":"Ferreira","year":"2021","journal-title":"Intern Emerg Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s10620-021-06982-8","article-title":"Stress hyperglycemia is independently associated with persistent organ failure in acute pancreatitis","volume":"10","author":"Yang","year":"2021","journal-title":"Dig Dis Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1186\/s12883-021-02512-1","article-title":"Persistent hyperglycemia is a useful glycemic pattern to predict stroke mortality: a systematic review and meta-analysis","volume":"21","author":"Hou","year":"2021","journal-title":"BMC Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s11739-020-02507-9","article-title":"The association of diabetes and hyperglycemia with sepsis outcomes: a population-based cohort analysis","volume":"16","author":"Zohar","year":"2021","journal-title":"Intern Emerg Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1097\/CCM.0000000000001650","article-title":"Admission hyperglycemia in critically ill sepsis patients: association with outcome and host response","volume":"44","author":"van Vught","year":"2016","journal-title":"Crit Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0152","DOI":"10.1097\/CCE.0000000000000152","article-title":"Stress hyperglycemia and mortality in subjects with diabetes and sepsis","volume":"2","author":"Fabbri","year":"2020","journal-title":"Crit Care Explor."},{"key":"B13","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.annemergmed.2011.03.052","article-title":"Diabetes is not associated with increased mortality in emergency department patients with sepsis","volume":"58","author":"Schuetz","year":"2011","journal-title":"Ann Emerg Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jcrc.2016.04.002","article-title":"A minimum blood glucose value less than or equal to 120 mg\/dL under glycemic control is associated with increased 14-day mortality in nondiabetic intensive care unit patients with sepsis and stress hyperglycemia","volume":"34","author":"Chan","year":"2016","journal-title":"J Crit Care."},{"key":"B15","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jcrc.2011.06.011","article-title":"Stress hyperglycemia may not be harmful in critically ill patients with sepsis","volume":"27","author":"Tiruvoipati","year":"2012","journal-title":"J Crit Care."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.3390\/ijms17091586","article-title":"Differential impact of hyperglycemia in critically ill patients: significance in acute myocardial infarction but not in sepsis?","volume":"17","author":"Wernly","year":"2016","journal-title":"Int J Mol Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1177\/0885066619889322","article-title":"Blood glucose levels and mortality in patients with sepsis: dose-response analysis of observational studies","volume":"36","author":"Wang","year":"2021","journal-title":"J Intensive Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jcrc.2018.03.012","article-title":"Early glycemia and mortality in critically ill septic patients: interaction with insulin-treated diabetes","volume":"45","author":"Magee","year":"2018","journal-title":"J Crit Care."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.1097\/CCM.0b013e3181810378","article-title":"Glucose variability and mortality in patients with sepsis","volume":"36","author":"Ali","year":"2008","journal-title":"Crit Care Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1056\/NEJMoa070716","article-title":"Intensive insulin therapy and pentastarch resuscitation in severe sepsis","volume":"358","author":"Brunkhorst","year":"2008","journal-title":"N Engl J Med."},{"key":"B21","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":"NICE-SUGAR Study","year":"2009","journal-title":"N Engl J Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"S144","DOI":"10.2337\/dc18-S014","article-title":"Diabetes care in the hospital: standards of medical care in diabetes-2018","volume":"41","year":"2018","journal-title":"Diabetes Care"},{"key":"B23","unstructured":"JohnsonA\n            BulgarelliL\n            PollardT\n            HorngS\n            CeliLA\n            MarkR\n          MIMIC-IV (version 1.0) PhysioNet2021"},{"key":"B24","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":"J Am Med Assoc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ajem.2020.02.002","article-title":"Efficacy and safety of corticosteroids for septic shock in immunocompromised patients: a cohort study from MIMIC","volume":"42","author":"Lu","year":"2021","journal-title":"Am J Emerg Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1026","DOI":"10.1097\/CCM.0000000000002590","article-title":"Diabetes is not associated with increased 90-day mortality risk in critically ill patients with sepsis","volume":"45","author":"van Vught","year":"2017","journal-title":"Crit Care Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"n422","DOI":"10.1136\/bmj.n422","article-title":"Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study","volume":"372","author":"Johannesen","year":"2021","journal-title":"BMJ."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.3760\/cma.j.cn112150-20200804-01092","article-title":"Application of restricted cube spline in cox regression model","volume":"54","author":"Wei","year":"2020","journal-title":"Chin J Prev Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"k2575","DOI":"10.1136\/bmj.k2575","article-title":"Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: prospective US cohort study","volume":"362","author":"Lee","year":"2018","journal-title":"BMJ."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1097\/CCM.0b013e31818b38d2","article-title":"Glycemic variability: a strong independent predictor of mortality in critically ill patients","volume":"36","author":"Krinsley","year":"2008","journal-title":"Crit Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"R37","DOI":"10.1186\/cc12547","article-title":"Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study","volume":"17","author":"Krinsley","year":"2013","journal-title":"Crit Care."},{"key":"B32","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1097\/CCM.0b013e3181cc4be9","article-title":"Glucose variability is associated with intensive care unit mortality","volume":"38","author":"Hermanides","year":"2010","journal-title":"Crit Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13613-020-0635-3","article-title":"Higher glycemic variability within the first day of ICU admission is associated with increased 30-day mortality in ICU patients with sepsis","volume":"10","author":"Chao","year":"2020","journal-title":"Ann Intensive Care."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e33849","DOI":"10.5812\/aapm.33849","article-title":"Predisposing factors for hypoglycemia and its relation with mortality in critically ill patients undergoing insulin therapy in an intensive care unit","volume":"6","author":"Mahmoodpoor","year":"2016","journal-title":"Anesth Pain Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"171","DOI":"10.2174\/1573399815999190619141622","article-title":"Impact of glycemic variability and hypoglycemia on the mortality and length of hospital stay among elderly patients in Brazil","volume":"16","author":"Bruginski","year":"2020","journal-title":"Curr Diabetes Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1089\/dia.2017.0306","article-title":"Relation between hypoglycemia and glycemic variability in type 2 diabetes patients with insulin therapy: a study based on continuous glucose monitoring","volume":"20","author":"Uemura","year":"2018","journal-title":"Diabetes Technol Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1177\/0885066613511048","article-title":"The effect of a hypoglycemia treatment protocol on glycemic variability in critically ill patients","volume":"30","author":"Arnold","year":"2015","journal-title":"J Intensive Care Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1097\/CCM.0b013e3181c02726","article-title":"Diabetes does not alter mortality or hemostatic and inflammatory responses in patients with severe sepsis","volume":"38","author":"Stegenga","year":"2010","journal-title":"Crit Care Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2337\/dc19-0963","article-title":"Association between preoperative blood glucose level and hospital length of stay for patients undergoing appendectomy or laparoscopic cholecystectomy","volume":"44","author":"Chiang","year":"2021","journal-title":"Diabetes Care."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1016\/j.ijcard.2012.04.053","article-title":"Non-linear contribution of glucose measures to cardiovascular diseases and mortality: reclassifying the Framingham's risk categories: a decade follow-up from the Tehran lipid and glucose study","volume":"167","author":"Yadegari","year":"2013","journal-title":"Int J Cardiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s00134-014-3287-7","article-title":"Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality","volume":"40","author":"Plummer","year":"2014","journal-title":"Intensive Care Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"590","DOI":"10.5811\/westjem.2013.4.14296","article-title":"Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department","volume":"14","author":"Soleimanpour","year":"2013","journal-title":"West J Emerg Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/dom.14609","article-title":"Performance of intermittently scanned continuous glucose monitoring systems in people with type 1 diabetes: a pooled analysis","volume":"24","author":"Moser","year":"2022","journal-title":"Diabetes Obes Metab."}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.857368\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T02:35:31Z","timestamp":1651199731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.857368\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":43,"alternative-id":["10.3389\/fpubh.2022.857368"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2022.857368","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]},"article-number":"857368"}}