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In the critically ill patient, diabetes predicts mortality independent of statin therapy but is not associated with acute lung injury: A cohort study*

Koh, Gavin C. K. W. MRCP; Vlaar, Alexander P. J. MD; Hofstra, Jorrit J. MD; de Jong, H. Katrien MD; van Nierop, Samuel; Peacock, Sharon J. PhD; Wiersinga, W. Joost MD; Schultz, Marcus J. MD; , PhD; Juffermans, Nicole P. MD

doi: 10.1097/CCM.0b013e31824e1696
Clinical Investigations

Objectives: Patients with diabetes mellitus form 23%–30% of published cohorts of critically ill patients. Conflicting published evidence links diabetes mellitus to both higher and lower mortality. Other cohort studies suggest that diabetes mellitus protects against acute lung injury. We hypothesized that diabetes mellitus is an independent risk factor for mortality. We further hypothesized that diabetes mellitus is a risk factor for cardiac overload and not for acute lung injury.

Design: Retrospective cohort study.

Setting: The intensive care unit of a tertiary referral hospital.

Patients: From November 1, 2004, to October 1, 2007, a cohort of patients admitted ≥48 hrs to the intensive care unit.

Interventions: None.

Measurements and Main Results: Of 2,013 patients, 317 had diabetes mellitus. Ninety-day mortality was higher in the diabetes mellitus patients compared to patients without diabetes mellitus (hazard ratio 1.53, 95% confidence interval 1.29–1.80). This association strengthened after adjusting for confounders and for medication (hazard ratio 1.53, 95% confidence interval 1.07–2.17).We found no association between diabetes mellitus and acute lung injury (relative risk ratio 1.01, 95% confidence interval 0.78–1.32; adjusted relative risk ratio 0.99, 95% confidence interval 0.75–1.31), but diabetes mellitus was a risk factor for cardiac overload (relative risk ratio 1.91, 95% confidence interval 1.30–2.81; adjusted relative risk ratio 1.45, 95% confidence interval 0.97–2.18). Statins were associated with both a reduced risk of mortality (hazard ratio 0.74, 95% confidence interval 0.63–0.87; adjusted hazard ratio 0.53, 95% confidence interval 0.44–0.64) and a decreased risk of developing acute lung injury (relative risk ratio 0.71, 95% confidence interval 0.56–0.89; adjusted relative risk ratio 0.61, 95% confidence interval 0.47–0.79).

Conclusions: Diabetes mellitus is an independent risk factor for mortality in critically ill patients and failure to adjust for statins underestimates the size of this association. Diabetes mellitus is not associated with acute lung injury but is associated with cardiac overload. A diagnosis of cardiac overload excludes a diagnosis of acute lung injury. Investigators who do not account for cardiac overload as a competing alternative outcome may therefore falsely conclude that diabetes mellitus protects from acute lung injury.

From the Center for Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine (GCKWK, HKdJ, WJW) and Laboratory of Experimental Intensive Care and Anesthesiology (APJV, JJH, MJS, NPJ), Academic Medical Center, Amsterdam, The Netherlands; the Faculty of Tropical Medicine (GCKWK, SJP), Mahidol University, Bangkok, Thailand; the Department of Medicine (GCKWK, SJP), Addenbrooke’s Hospital, Cambridge, United Kingdom; the Department of Infection and Tropical Medicine (GCKWK), Heartlands Hospital, Birmingham, United Kingdom; and the University of Amsterdam (SvN), Amsterdam, The Netherlands.

*See also p. 1981.

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This work was performed at the Academic Medical Center, Amsterdam, The Netherlands.

Dr. Koh is funded by the Wellcome Trust of Great Britain (086532/Z/08/Z). Dr. Peacock is supported by the NIHR Cambridge Biomedical Research Centre. Dr. Wiersinga is supported by a VENI grant from the Netherlands Organization for Medical Research. The authors have not disclosed any potential conflicts of interest.

For information regarding this article and for reprints, E-mail: gavin.koh@gmail.com

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins