- acute
- critical care
- chronic obstructive pulmonary disease
- myocardial infarction
- stress hyperglycaemia
- stroke
Key points
Hyperglycaemia is common in the acute care setting, reflecting high prevalence of known or undiagnosed diabetes mellitus (DM) and the physiological effects of acute illness, causing ‘stress hyperglycaemia’
There is a continuous association between increasing blood glucose concentrations and worsening clinical outcomes in diverse acute illnesses although causality has not been proven
UK guidelines currently recommend blood glucose control in patients admitted with acute coronary syndrome or stroke
Patients with acute hyperglycaemia without a prior diagnosis of DM should have HbA1c measured both prior to discharge to determine diagnosis or risk of diabetes and at subsequent follow-up
Hyperglycaemia is common in the acute care setting. In a study of 2,030 adults admitted acutely to hospital, 32% of whom had no prior history of diabetes mellitus (DM), 38% had a fasting blood glucose above 7.0 mmol/l or a random glucose above 11.1 mmol/l.1 Patients with acute hyperglycaemia with no prior diagnosis of diabetes may either have stress hyperglycaemia precipitated by the physiological stress of acute illness or undiagnosed DM. This article provides an overview of the mechanisms, impact and diagnosis of acute hyperglycaemia and outlines recommendations for treatment and follow-up.
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
Diabetic ketoacidosis
DKA is a complex disordered metabolic state characterised by hyperglycaemia, acidosis and ketonaemia,3 most commonly occurring in patients with new or known type 1 DM due to insulin deficiency or inadequate insulin replacement. Although most often seen in younger people, DKA can occur in elderly patients with long-standing type 1 diabetes. It can also affect patients with type 2 diabetes with relative insulin deficiency (ketosis-prone type 2 diabetes) in combination with severe illness. Clinical features include polyuria, polydipsia, hyperventilation and abdominal pain. Recommended management includes urgent replacement of insulin and fluids, guided by venous (rather than arterial) bicarbonate and pH, with blood ketone testing (using bedside meters).3
Hyperglycaemic hyperosmolar syndrome
HHS typically presents in older patients with type 2 diabetes and has a high mortality. It is characterised by hyperosmolality and dehydration without significant ketoacidosis. Other common clinical features include lethargy and neurological deficit. Management priorities include rehydration, thromboprophylaxis and treatment of any precipitating cause (often infection).
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 (HbA1c) 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 HbA1c 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).
Summary of international recommendations for treatment of hyperglycaemia in acute stroke.
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
Prior diagnosis of diabetes
Patients with diabetes accounted for 9.7% of all inpatients in one UK hospital. It is well recognised that the stress of acute illness may exacerbate hyperglycaemia in this population. Acute adjustments in therapy may be required to control blood glucose. Any adjustments should be monitored following resolution of the acute illness to avoid subsequent overtreatment.
Undiagnosed diabetes mellitus
It is estimated that about half a million people in the UK have undiagnosed diabetes. Hyperglycaemia in the acute setting presents an opportunity to identify these individuals and offer appropriate treatment to delay or prevent the onset of diabetic complications. Given that diabetes is a risk factor for macrovascular disease, acute admissions with stroke, transient ischaemic attack, ACS or peripheral vascular disease should prompt investigation. Other populations at risk of diabetes include those who are obese or taking oral corticosteroids. Recent US guidelines recommend that all patients should undergo laboratory glucose testing on admission.17
Diagnosis of diabetes mellitus in the acute care setting
Some measurements taken in acute care and their utility are described in Tables 2 and 3. Stress hyperglycaemia is common, so fasting and random blood glucose measurements in the first few days of acute illness may not be discriminatory in the absence of symptoms. An elevated HbA1c will indicate chronic hyperglycaemia preceding the acute illness, but a ‘normal’ HbA1c does not exclude DM. All patients without diabetes found to have hyperglycaemia in the acute setting should be reviewed on recovery to identify underlying glucose tolerance and determine whether any treatment is necessary (Table 4).
Investigations commonly used to identify hyperglycaemia/new-onset diabetes mellitus in the acute setting.
Interpretation of glycosylated haemoglobin (HbA1c) values.
Recommended follow-up for patients with hyperglycaemia in the acute setting.
Conclusions
Hyperglycaemia in the acute setting is common and frequently overlooked. In all contexts, acute hyperglycaemia is associated with poor clinical outcomes. Pragmatic guidelines for the treatment of acute hyperglycaemia exist, but further research and improved clinical awareness are required to reduce adverse outcomes and increase the pick-up of undiagnosed diabetes in the acute setting.
- © 2012 Royal College of Physicians
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