• Lonneke A van Vught, Maryse A Wiewel, Peter M C Klein Klouwenberg, Arie J Hoogendijk, Brendon P Scicluna, David S Y Ong, Olaf L Cremer, Janneke Horn, Marc M J Bonten, Marcus J Schultz, Tom van der Poll, and Molecular Diagnosis and Risk Stratification of Sepsis Consortium.
• 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 2The Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 3Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. 4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands. 5Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 6Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 7Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
• Crit. Care Med. 2016 Jul 1; 44 (7): 1338-46.

ObjectivesTo investigate whether admission hyperglycemia is associated with the presentation and/or outcome of sepsis, what the influence of hyperglycemia is on key host responses to sepsis, and whether hyperglycemia differentially affects patients with diabetes mellitus.Design And SettingA substudy of a prospective observational cohort study was conducted in the intensive care of two tertiary hospitals between January 2011 and July 2013.PatientsOf all consecutive critically ill sepsis patients, admission glucose was used to stratify patients in euglycemia (71-140 mg/dL), mild hyperglycemia (141-199 mg/dL), and severe hyperglycemia (≥ 200 mg/dL), and patients with hypoglycemia were excluded. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured on admission.Measurements And Main ResultsOf 987 sepsis patients with admission glucose levels greater than 70 mg/dL, 519 (52.6%) had normal glucose levels, 267 (27.1%) had mild, and 201 (20.4%) severe hyperglycemia. Admission hyperglycemia was accompanied by mitigated alterations in plasma host response biomarker levels indicative of activation of the cytokine network, the vascular endothelium, and the coagulation system in patients without a history of diabetes. Severe, but not mild, admission hyperglycemia was associated with increased 30-day mortality (adjusted hazard ratio, 1.66 [95% CI, 1.24-2.23]), in both patients without diabetes (adjusted hazard ratio, 1.65 [95% CI, 1.12-2.42]) and with diabetes (adjusted hazard ratio, 1.91 [95% CI, 1.01-3.62]).ConclusionAdmission hyperglycemia is associated with adverse outcome of sepsis irrespective of the presence or absence of preexisting diabetes by a mechanism unrelated to exaggerated inflammation or coagulation.

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