Impact of glucocorticoids on insulin resistance in the critically ill

Abstract

Glucocorticoids (GCs) have been shown to reduce insulin sensitivity in healthy individuals. Widely used in critical care to treat a variety of inflammatory and allergic disorders, they may inadvertently exacerbate stress-hyperglycaemia. This research uses model-based methods to quantify the reduction of insulin sensitivity from GCs in critically ill patients, and thus their impact on glycaemic control. A clinically validated model-based measure of insulin sensitivity (SI) was used to quantify changes between two matched cohorts of 40 intensive care unit (ICU) patients who received GCs and a control cohort who did not. All patients were admitted to the Christchurch hospital ICU between 2005 and 2007 and spent at least 24 hours on the SPRINT glycaemic control protocol. A 31% reduction in whole-cohort median insulin sensitivity was seen between the control cohort and patients receiving glucocorticoids with a median dose equivalent to 200mg/day of hydrocortisone per patient. Comparing percentile-patients as a surrogate for matched patients, reductions in median insulin sensitivity of 20, 25, and 21% were observed for the 25th, 50th and 75th-percentile patients. All these cohort and per-patient reductions are less than or equivalent to the 30-62% reductions reported in healthy subjects especially when considering the fact that the GC doses in this study are 1.3-4 times larger than those in studies of healthy subjects. This reduced suppression of insulin sensitivity in critically ill patients could be a result of saturation due to already increased levels of catecholamines and cortisol common in critically illness. Virtual trial simulation showed that reductions in insulin sensitivity of 20-30% associated with glucocorticoid treatment in the ICU have limited impact on glycaemic control levels within the context of the SPRINT protocol.