Intensive blood glucose control in acute and prolonged critical illness: endogenous secretion contributes more to plasma insulin than exogenous insulin infusion František Duška a, ⁎ , Michal Anděl b a Department of Anesthesia and Critical Care Medicine, The Third Faculty of Medicine, Charles University, 11000 Prague, Czech Republic, EU b Department of Internal Medicine II, The Third Faculty of Medicine, Charles University, 11000 Prague, Czech Republic, EU Received 20 June 2007; accepted 17 January 2008 Abstract We investigated the contribution of impaired insulin secretion (observed as dynamics of C-peptide) and insulin resistance (measured by euglycemic clamps) to glucose dysregulation in 20 critically ill patients after severe trauma during feeding and intensive glucose control with intravenous insulin. Between the fourth and seventh day when insulin sensitivity is lowest, insulin secretion is highest and supranormal despite tight control of blood glucose by exogenous insulin. Afterward, plasma C-peptide decreases together with an improvement in insulin sensitivity. Multiple regression analysis revealed that plasma insulin is determined more by endogenous secretion than insulin infusion, even during the acute phase when exogenous insulin requirements are high. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Hyperglycemia in critically ill nondiabetic patients is very common [1], and most intensive care unit (ICU) patients probably benefit from tight glucose control by continuous intravenous (IV) insulin infusion [2,3]. Thus, most ICU patients are treated with continuous IV insulin infusion. We asked to what extent this treatment influenced plasma insulin concentration in comparison with endogenous insulin secretion. We also attempted to describe the changes of insulin resistance during the transition from an acute to prolonged phase of critical illness. 2. Methods We conducted a prospective study on multiple trauma patients (n = 20; male = 17; female = 3; age, 40 ± 16 years; body mass index, 27 ± 4 kg m -2 ; Injury Severity Scale = 39 ± 14; Acute Physiology and Chronic Health Evaluation II score, 24 ± 8) who were expected to require ventilator support for at least 2 weeks, mainly because of severe head injury or chest trauma. We excluded patients expected to die or having diabetes. The Ethics Committee approved the protocol, and the closest relatives of the subjects gave their informed consent. During the study, 2 patients received hydrocortisone in substitution doses (up to 150 mg/d) for a period up to 5 days. Only norepinephrine was used as a vasopressor: the number of treated patients declined from 15 (75%) at day 4 (average dose, 0.07 ± 0.05 μg kg -1 min -1 ) to 1 (5%) at day 17. No other drugs with a known influence on insulin secretion or sensitivity were given to study subjects, excluding β-blockers. The study subjects were fed preferably by the enteral route (Diason Low Energy; Nutricia, Prague, Czech Republic) and supplemented with parenteral nutrition to reach a nutritional goal of 1.5 g amino acids per kilogram per day and 80% of energy expenditure measured daily by indirect calorimetry. The proportion of calories provided enterally increased from ~30% at the beginning of the study to ~60% in the end. Blood glucose was measured in at least 3-hour intervals and corrected with IV insulin (Actrapid; Novo Nordisk, Copenhagen, Denmark) according to a nurse-directed protocol [4]. Plasma insulin Available online at www.sciencedirect.com Metabolism Clinical and Experimental 57 (2008) 669 – 671 www.metabolismjournal.com ⁎ Corresponding author. E-mail address: fduska@yahoo.com (F. Duška). 0026-0495/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2008.01.001