Stress hyperglycaemia

Abstract

Results of randomised controlled trials of tight glycaemic control in hospital inpatients might vary with population and disease state. Individualised therapy for different hospital inpatient populations and identification of patients at risk of hyperglycaemia might be needed. One risk factor that has received much attention is the presence of pre-existing diabetes. So-called stress hyperglycaemia is usually defined as hyperglycaemia resolving spontaneously after dissipation of acute illness. The term generally refers to patients without known diabetes, although patients with diabetes might also develop stress hyperglycaemia-a fact overlooked in many studies comparing hospital inpatients with or without diabetes. Investigators of several studies have suggested that patients with stress hyperglycaemia are at higher risk of adverse consequences than are those with pre-existing diabetes. We describe classification of stress hyperglycaemia, mechanisms of harm, and management strategies.

Conflict of interest statement

Conflicts of interest

KMD has received grant support from NovoNordisk, Diramed, and Tolerx, and has consulted with Eli Lilly, Diramed, and Glycomark. SSB and J-CP declare that they have no conflicts of interest.

Figures

Figure 1

Expanded view of stress hyperglycaemia

Figure 2. Multifactorial causes of hospital-related hyperglycaemia

Causal factors are specific to the patient, their illness, and their treatment. Hyperglycaemia can exacerbate some illness-specific factors and increase need for treatment-specific factors, leading to a vicious cycle by which hyperglycaemia causes further hyperglycaemia. HPA=hypothalamic-pituitary-adrenal axis.

Figure 3. Glucose metabolism in stress hyperglycaemia

Stress hyperglycaemia is characterised by increased whole-body glucose uptake, mostly caused by non-insulin-mediated glucose transport via GLUT-1 transporters to body tissues. Insulin-mediated glucose uptake is reduced (insulin resistance), largely due to postreceptor insulin signalling defects that result in reduced GLUT-4-mediated glucose transport in insulin sensitive tissues such as liver, muscle, and fat. Muscle glycogen storage is also reduced. Glucose production is generally up-regulated, mainly a result of unregulated hepatic gluconeogenesis. Finally, once inside a target cell, glucose is oxidised readily but non-oxidative metabolism (predominantly glycogen storage) is impaired.

Figure 4. Overlapping mechanisms of harm in hyperglycaemia

Mechanisms of harm relate to acute or chronic complications of hyperglycaemia. NFkB = nuclear factor κ B. ERK = extracellular signal regulated kinase. MAPK=microtubule associated protein kinase. PKC = protein kinase C. AGE = advanced glycosylation endproducts. CVA = cerebrovascular accident. AMI = acute myocardial infarction.