Hyperglycemia at admission to the intensive care unit is associated with elevated serum concentrations of interleukin-6 and reduced ex vivo secretion of tumor necrosis factor-α*

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Abstract
The aim of the study was to investigate the association between admission blood glucose concentrations and immune function variables and its correlation to mortality rate in patients of a medical intensive care unit. Prospective, observational study. Medical intensive care unit of a university hospital. Patients were 189 consecutive critically ill patients in the medical intensive care unit. At admission to the intensive care unit, serum concentrations of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α were measured with immunometric assays. Additionally, ex vivo secretion of tumor necrosis factor-α after stimulation with lipopolysaccharide in a whole blood assay and cytometric human leukocyte antigen-DR expression on monocytes were determined in all study subjects. Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28 were calculated for the first day in the intensive care unit. The relationships between blood glucose concentrations and immunologic variables were analyzed using univariate and multivariate statistical methods. Overall, 75 patients (39.7%) presented with hyperglycemia. An elevated blood glucose concentration at admission was related to an increased risk of mortality in the intensive care unit (odds ratio, 2.6; p = .009). At univariate and multivariate analysis, hyperglycemia was associated with increased serum concentrations of interleukin-6 (p < .05), a reduced ex vivo production of tumor necrosis factor-α (p < .01), and a history of diabetes mellitus (p < .05), whereas other clinical (including Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28) and immunologic variables were not statistically related to blood glucose. Our main findings show that admission hyperglycemia is statistically related to distinct changes of humoral and cellular immune functions. Furthermore, elevated glucose concentrations at admission are associated with increased intensive care unit mortality rate in a medical intensive care unit. Although these data do not explain cause and effect, our results provide a strong rationale for studying the immunologic effects of strict glycemic control in the intensive care unit during the course of critical illness.