Hyperglycaemia in the acute care setting

Pathophysiology

Mechanisms underlying stress hyperglycaemia include increased release of counter-regulatory hormones and pro-inflammatory cytokines, leading to a rise in insulin resistance and gluconeogenesis. Specific treatments such as glucocorticoids or enteral nutrition, as well as underlying poor pancreatic reserve or insulin resistance, increase the risk of stress hyperglycaemia. A vicious cycle then develops, with hyperglycaemia exacerbating inflammation and oxidative stress which drive worsening hyperglycaemia.²

Impact of acute hyperglycaemia

Acute hyperglycaemia may be an immediate life-threatening emergency due to decompensated or undiagnosed diabetes or a stress response to acute illness (stress hyperglycaemia). Stress hyperglycaemia is also associated with poor outcomes. Patients with hyperglycaemia may be asymptomatic or experience classic symptoms of polyuria, polydipsia and lethargy. Where hyperglycaemia is prolonged, patients may also report recurrent infections, weight loss and blurred vision.

It is crucial to identify hyperglycaemic emergencies such as diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndrome (HHS) and treat rapidly according to national guidelines. The management of stress hyperglycaemia is less clearly defined and remains the subject of research.

Hyperglycaemic emergencies

Stress hyperglycaemia

Elevated blood glucose during acute illness is associated with poor outcomes from diverse conditions including myocardial infarction (MI),^4,5 stroke⁶ and respiratory infection.^7,8 The relationship between blood glucose and poor outcomes is continuous, so it is difficult to identify a cut-off value above which blood glucose levels are considered abnormal. However, a reasonable definition for stress hyperglycaemia is random blood glucose above 7.0 mmol/l. Acute hyperglycaemia has a greater adverse impact on outcomes in patients without prior DM than in those with diabetes.^1,5 At present it is not clear whether hyperglycaemia directly causes poor outcomes or is simply a marker of acute illness severity. Potential adverse effects of hyperglycaemia include increased oxidative stress, impaired endothelial function and activation of the coagulation pathway.

Hyperglycaemia in acute coronary syndrome

In all patients with MI, admission glucose is a strong predictor of increased mortality and in-hospital complications. A review of 15 studies found that the relationship between hyperglycaemia and poor outcomes was particularly strong for patients without prior diabetes.⁵ In non-diabetic patients, risk of death post-MI was 3.9 times greater in those with admission blood glucose 6.1–8.0 mmol/l, and risk of heart failure or cardiogenic shock three-fold higher in those with admission glucose 8–10 mmol/l than in those with lower admission glucose levels.⁵ Similarly, persistently elevated glucose levels during admission are associated with increased in-hospital mortality.⁹

Despite a clear association between hyperglycaemia and poor outcomes, studies of intensive glycaemic control in acute MI (including the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) and the Hyperglycaemia: Intensive Insulin Infusion in Infarction (HI-5) studies) have failed to identify an optimal treatment strategy. Factors that may account for conflicting trial evidence include inadequate patient recruitment and glucose control. In this context, the National Institute for Clinical Excellence recommends initiating treatment with a dose-adjusted insulin infusion in patients admitted to hospital with ACS when blood glucose is above 11.0 mmol/l.

A significant proportion of individuals with hyperglycaemia during ACS will have undiagnosed diabetes or glucose intolerance. All patients with hyperglycaemia without prior diagnosis of diabetes should therefore be offered:⁹

• glycosylated haemoglobin (HbA_1c) test before discharge

• fasting glucose test no earlier than four days after onset of ACS

• lifestyle advice

• counselling regarding symptoms of hyperglycaemia

• annual general practitioner monitoring of HbA_1c and fasting glucose levels.

Hyperglycaemia in stroke

Hyperglycaemia is a common finding in acute ischaemic stroke – reported in 32% of patients without prior diabetes.¹⁰ A systematic review concluded that high glucose levels predict increased in-hospital mortality and poor functional recovery in stroke survivors.¹¹ Hyperglycaemia may exacerbate brain injury and induce cell lysis in metabolically-challenged tissue through a variety of mechanisms, including:

• anaerobic metabolism

• free radical generation, and

• increased blood-brain-barrier permeability.¹²

To date, only one underpowered clinical trial has investigated the effect of glycaemic control on stroke outcome, finding no clinical benefit.¹³ Despite this, and perhaps in view of the available theoretical evidence,¹² various guidelines advocate the treatment of hyperglycaemia in this population (Table 1).

Hyperglycaemia in respiratory infection

Acute hyperglycaemia is particularly common in patients with exacerbations of chronic obstructive pulmonary disease (COPD) due to physiological stress, underlying impaired glucose intolerance and treatment with oral glucocorticoids. In two separate studies, 50% of patients hospitalised with acute COPD exacerbations had random blood glucose of 7 mmol/l or above. Each 1 mmol/l increase in blood glucose increased absolute risk of death or prolonged hospital stay by 15%.⁸ Hyperglycaemia also predicts failure of non-invasive ventilation after initial success.¹⁵ Prospective studies are currently underway to determine whether blood glucose control can improve COPD exacerbation outcomes.

Hyperglycaemia in diabetes mellitus