• Palash Kar, Mark P Plummer, Rinaldo Bellomo, Alicia J Jenkins, Andrzej S Januszewski, Marianne J Chapman, Karen L Jones, Michael Horowitz, and Adam M Deane.
• 1Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia.2Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.3Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.4School of Medicine, The University of Melbourne, Melbourne, VIC, Australia.5Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.6National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.7National Health and Medical Research Council Centre of Research Excellence (CRE) in the Translation of Nutritional Science into Good Health, University of Adelaide, Adelaide, SA, Australia.8Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
• Crit. Care Med. 2016 Sep 1; 44 (9): 1695-703.

ObjectivesThe optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a " liberal" approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe.DesignProspective, open-label, sequential-period exploratory study.SettingMedical-surgical ICU.PatientsDuring sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission).InterventionDuring the "standard care" period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the "liberal" period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L.Measurements And Main ResultsTime-weighted mean glucose concentrations and the number and duration of moderate (< 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucoseday 0-7, standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L; p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L; p < 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19-1.13]; p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%]; p < 0.01). Biomarker data and clinical outcomes were similar.ConclusionsIn critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.

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