In 2001, Van den Berghe and colleagues [1] reported reduced mortality and morbidity in patients admitted to the surgical intensive care unit (ICU) who were randomly assigned to intensive insulin therapy (n=765). This was initiated when blood glucose was >6.1 mmol/l (110 mg/dl), with a goal glucose level of 4.4–6.1 mmol/l (80–110 mg/dl). The study group was compared with patients randomised to conventional insulin therapy (n=783), which was initiated when blood glucose was >11.9 mmol/l (215 mg/dl), with a goal glucose level of 10.0–11.1 mmol/l (180–200 mg/dl). The study showed that ICU mortality decreased from 8.0 to 4.6%, attributable to an effect among patients who remained in the ICU for more than 5 days, in the patients who received intensive insulin therapy. Hospital mortality was decreased from 10.9 to 7.2%. Several morbidity endpoints were also decreased in the intensive insulin therapy patients (Table 1), but hypoglycaemia (blood glucose <2.2 mmol/l [40 mg/dl]) was increased six-fold. Multivariate logistic regression analysis indicated that lower blood glucose concentrations, rather than higher insulin doses, were related to reduced mortality, critical illness polyneuropathy, bacteraemia, inflammation and anaemia (but not acute renal failure) [2]. Potential mechanisms of the beneficial effects of intensive insulin therapy, which have been reviewed [3], are those possibly related to lower glucose or to higher insulin levels. The former include improved macrophage/neutrophil function [3], improved coagulation and fibrinolysis [2], and reduced superoxide production (which might relate to improved hepatocyte mitochondrial function [3, 4]); if extended to neurons, the latter might explain prevention of critical illness polyneuropathy [3, 5]. In addition to anabolic and anti-inflammatory actions [3], other beneficial effects of insulin may have been operative [3]. In a subset of patients requiring intensive care for more than 7 days, lipid, rather than glucose, control was associated with beneficial effects of intensive insulin therapy on morbidity and mortality [6]. Finally, the findings of reduced levels of circulating adhesion molecules, reduced inducible nitric oxide synthase gene expression in post-mortem liver and skeletal muscle, and lowered circulating nitric oxide levels associated with intensive insulin therapy suggest protection of endothelial function [7]. Among other issues [8], limitations of the surgical ICU study included concerns that it was not strictly blinded and that cardiac surgery patients were over-represented [1]; the latter issue has since been addressed in a study on intensive insulin therapy in medical ICU patients [9]. The experimental design was similar to that of the surgical ICU study. Patients were again randomly assigned to intensive insulin therapy (n=595; 98% treated with a median insulin dose of 59 U per ICU day) or to conventional insulin therapy (n=605; 70% treated with a median insulin dose of 10 U per ICU day). Compared with conventional insulin therapy, intensive therapy reduced some of the morbidity endpoints, including acquired kidney injury, time to weaning from mechanical ventilation, and time to discharge from the ICU and from the hospital (Table 1). These were again attributable to an effect among patients who remained in the ICU for more than 5 days. However, in contrast to the surgical ICU findings, intensive insulin therapy did not decrease bacterDiabetologia (2006) 49:1722–1725 DOI 10.1007/s00125-006-0306-4
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Jan 1, 2023
Abhilasha Ahlawat + 2
