Hyperglycemia at admission to ICU is independently associated with increased serum levels of IL-6 and reduced ex vivo TNF-alpha production

Background

Hyperglycemia has been shown to be an independent risk factor of mortality in patients with stroke and myocardial infarction. Furthermore, strict control of hyperglycemia reduces mortality and rates of infectious complications in surgical ICU patients. The aim of the present study was to investigate immunological changes in medical patients in relation to blood glucose at admission to ICU.

Patients and methods

Overall, 189 consecutive medical ICU patients were enrolled. At admission, blood glucose and serum levels of IL-6, IL-8, IL-10, and TNF-alpha were measured. Furthermore, monocyte HLA-DR expression and ex vivo TNF-alpha production in whole blood after stimulation with LPS were determined. In all patients, SAPS II score was calculated for day of admission to ICU. Hyperglycemia was defined as a venous blood glucose > 126 mg/dl in fasting and > 200 mg/dl in nonfasting individuals. Frequencies in contingency tables were calculated with Fisher's exact test. Logistic regression was used with hyperglycemia as the dependent variable and immune parameters, SAPS II score, and history of diabetes as covariates.

Results

Overall mortality within the study period was 20.1%. Patients with hyperglycemia had an increased risk of mortality in the ICU compared with patients with normoglycemia at admission (29.3% vs 15.2%; OR = 2.3, P = 0.03). Sepsis according to Bone criteria was equally distributed between groups (14.3% vs 10.7%; P > 0.05). At logistic regression analysis, higher serum levels of IL-6, a reduced ex vivo production of TNF-alpha, and a history of diabetes were independently associated with hyperglycemia at admission to ICU (P = 0.007, P < 0.001, P = 0.002, respectively), while IL-8, IL-10, TNF-alpha, monocyte HLA-DR expression and the SAPS II score were not associated with increased blood glucose levels (all P > 0.05).

Conclusions

Independent of SAPS II score and underlying disease, hyperglycemia at admission to ICU is associated with immunological changes that are frequently observed in critically ill patients ('immunoparalysis'). Particularly, a reduced ex vivo production of TNF-alpha might contribute to the increased risk for infectious complications and death in patients with acute and chronic hyperglycemia.