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Admission Hyperglycemia in Critically Ill Sepsis Patients: Association With Outcome and Host Response*

van Vught, Lonneke A. MD; Wiewel, Maryse A. MD; Klein Klouwenberg, Peter M. C. MD, PharmD, PhD; Hoogendijk, Arie J. PhD; Scicluna, Brendon P. PhD; Ong, David S. Y. MD, PharmD, PhD; Cremer, Olaf L. MD, PhD; Horn, Janneke MD, PhD; Bonten, Marc M. J. MD, PhD; Schultz, Marcus J. MD, PhD; van der Poll, Tom MD, PhD

doi: 10.1097/CCM.0000000000001650
Clinical Investigations
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SDC

Objectives: To 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 Setting: A substudy of a prospective observational cohort study was conducted in the intensive care of two tertiary hospitals between January 2011 and July 2013.

Patients: Of 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 Results: Of 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]).

Conclusion: Admission 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.

Supplemental Digital Content is available in the text.

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.

*See also p. 1433.

Drs. van Vught, Wiewel, Klein Klouwenberg, Cremer, Bonten, Schultz, and van der Poll substantially contributed to the design of the study. Drs. van Vught, Wiewel, and Klein Klouwenberg acquired all the data. Dr. Hoogendijk performed all laboratory measurements, and Dr. Scicluna performed the microarray analysis. Dr. van Vught is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs. van Vught, van der Poll, Scicluna, Hoogendijk, and Wiewel were involved in the interpretation of the data. Drs. van Vught and van der Poll drafted the article, and all authors reviewed and revised it critically for important intellectual content. All authors gave final approval of this version to be submitted.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported by the Center for Translational Molecular Medicine (http://www.ctmm.nl), project Molecular Diagnosis and Risk Stratification of Sepsis (grant 04I-201).

Dr. van Vught disclosed that this work was supported by the Center for Translational Molecular Medicine (http://www.ctmm.nl), project Molecular Diagnosis and Risk Stratification of Sepsis (MARS) (grant 04I-201). Dr. Cremer’s institution received funding from the Center of Translational Molecular Medicine (CTMM) (project MARS). The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: l.a.vanvught@amc.uva.nl

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