We searched PubMed from 1975 to Dec 15, 2011, with the terms (and synonyms) “stroke”, “cerebral ischaemia”, “cerebral infarction”, “hyperglycaemia”, “diabetes”, “glucose”, and “insulin”, in combination with the key terms “epidemiology”, “risk factors”, “treatment”, “prevention”, and “outcome”. We only searched for papers published in English. We also searched reference lists of reports identified with this strategy for relevant publications. Furthermore, we searched the Stroke Trials Registry,
ReviewDiabetes, hyperglycaemia, and acute ischaemic stroke
Introduction
Diabetes and ischaemic stroke are common disorders that often arise together. Worldwide, 347 million people have diabetes,1 and the type 1 and type 2 forms are the most typical (panel 1). Diabetes is a leading cause of renal failure, coronary heart disease, non-traumatic lower limb amputations, and visual impairment (figure 1). Stroke is the second leading cause of long-term disability in high-income countries and the second leading cause of death worldwide.18 In 2005, 16 million people had a first stroke and 5·7 million died because of the effects of stroke.19 The relation between disturbed glucose metabolism and ischaemic stroke is bidirectional. On the one hand, people with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, compared with people without diabetes.20 On the other hand, acute stroke can give rise to abnormalities in glucose metabolism, which in turn could affect outcome.21 Importantly, the relation between disturbed glucose metabolism and cerebrovascular disease is not restricted to acute ischaemic stroke. Diabetes is also associated with more insidious ischaemic damage to the brain, mainly manifesting as small-vessel disease and increased risk of cognitive decline and dementia.22 Moreover, a relation between admission hyperglycaemia and poor outcome has been noted for haemorrhagic stroke, in particular aneurysmal subarachnoid haemorrhage.23
In this Review, we describe the interplay between glucose metabolism and acute ischaemic stroke and focus on clinical implications for prevention and management in the acute stage. We address the epidemiology of the association between diabetes and stroke, highlighting potentially modifiable risk factors and long-term outcome. We review findings from many trials on prevention of stroke in people with diabetes, which suggest that rigorous assessment and treatment of associated risk factors can substantially reduce the risk of stroke in patients with diabetes. We then describe the cause, outcome, and management of hyperglycaemia at the time of an acute ischaemic stroke. Admission hyperglycaemia is a common risk factor for poor outcome after ischaemic stroke. However, much uncertainty surrounds the question of whether intensive glucose-lowering treatment after stroke benefits clinical outcome.
Section snippets
Diabetes and risk of stroke
Diabetes is an important risk factor for ischaemic stroke. In a meta-analysis of prospective studies (including 530 083 participants), the reported hazard ratio for ischaemic stroke was 2·3 (95% CI 2·0–2·7) in people with versus those without diabetes.20 Assuming a population-wide prevalence of diabetes of around 10%, these findings indicate a diabetes-attributable risk of stroke of around 12% (ie, one in eight or nine cases of stroke is attributable to diabetes).
The risk of stroke associated
Diabetes and long-term outcome after stroke
During the first 3 months after ischaemic stroke, mortality is not increased in patients with diabetes compared with those without.35, 36 However, mortality more than 1 year after stroke was slightly increased (hazard ratio 1·2, 95% CI 1·1–1·2); a similar finding was reported in patients younger than 50 years.36, 37 Furthermore, risk of recurrent stroke is raised (1·8, 1·2–2·8),38 which could be even more striking in patients with diabetes younger than 50 years.37 Finally, diabetes is
Diabetes and prevention of stroke
Several risk factors for stroke in patients with diabetes are potentially modifiable, in particular lifestyle factors, glucose concentrations, blood pressure, and dyslipidaemia, which have been targeted in several large randomised controlled trials (panel 2). Neurologists typically distinguish between primary prevention (eg, prevention of first stroke) and secondary prevention (eg, prevention after transient ischaemic attack or ischaemic stroke). However, this distinction is not always made in
Hyperglycaemia in acute ischaemic stroke
Hyperglycaemia arises in 30–40% of people with acute ischaemic stroke.76 Most of these individuals do not have a known history of diabetes mellitus.21 In some patients, hyperglycaemia reflects pre-existing but unrecognised diabetes, but more often it is the result of an acute stress response, typically named stress hyperglycaemia (panel 3). Glucose concentrations are raised in people with stress hyperglycaemia but revert to normal after discharge from hospital.77 Therefore, high levels of
Conclusions
Diabetes is associated with a doubling of the risk of stroke and with poor long-term outcome after ischaemic stroke. Therefore, neurologists should monitor glucose metabolism in all patients with ischaemic stroke. All individuals should be classified as either normoglycaemic or with stress hyperglycaemia, and with either newly diagnosed type 2 diabetes or known diabetes. Although the effectiveness of glucose-lowering treatment on clinical outcome has yet to be established, protocols are
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