Understanding insulin and nutrition administration in glycemic control with the right side of the brain

Abstract

Background Critically ill patients frequently experience stress-induced hyperglycaemia, leading to increased morbidity and mortality. Glycaemic control (GC) with insulin therapy alone has proven difficult, due to significant inter- and intra- patient variability in response to insulin therapy. This study reviews the problem and analyses the impact of physiological dynamics and patient variability on outcome glycemia. Methods A graphical model of metabolic dynamics is used to analyse the impact of fundamental glucose flux dynamics on insulin and nutrition administration in the context of maintaining a glycemic goal. It is used to delineate the limits of ability in controlling insulin and/or nutrition administration to achieve safe, effective glycemic control in critical illness in the presence of low insulin sensitivity and high insulin sensitivity variability. Results Insulin saturation limits insulin-mediated glucose uptake. At low insulin sensitivity, maintaining a glycemic target level requires reduced nutrition administration due to saturated insulin-mediated glucose uptake. Metabolic insulin sensitivity variability leads to insulin-mediated glucose uptake variability, requiring reduced nutrition administration at low insulin sensitivity and higher insulin doses to mitigate the risk of hypo- and hyper- glycemia. Conclusions This work reviews the clinical glycemic control problem using a graphically-based physiological analysis to show the need to control nutrition administration, along with insulin, to achieve safe, effective control. These reductions are necessary for highly insulin resistant patients, a condition typically occurring early in ICU stay. Glycemic control should directly control nutrition in addition to insulin to optimise all avenues of glucose flux and thus ensure safe, effective glycemic control.