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Stroke The Treatment of Diabetes after an Acute Ischaemic Stroke Geert Jan Biessels 1 and L Jaap Kappelle 1 1. Professor of Neurology, Department of Neurology, UMC Utrecht Stroke Centre and Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands Abstract People with diabetes are at increased risk of ischaemic stroke and outcome after stroke is worse. This paper reviews the treatment of patients with diabetes after ischaemic stroke. First, management of hyperglycaemia in the acute stage will be addressed. We will make the point that, despite the fact that admission hyperglycaemia is a common risk factor for poor outcome after ischaemic stroke, there is still much uncertainty about whether intensive glucose-lowering therapy after stroke benefits clinical outcome. Secondary prevention of further cardiovascular events after stroke is the other main topic of this review. We will show that there are important opportunities for the reduction of stroke risk in diabetes, through a rigorous evaluation and treatment of associated risk factors. Keywords Diabetes, ischaemic stroke, prevention, treatment, outcome Disclosure: Geert Jan Biessels consults for and receives research support from Boehringer Ingelheim. L Jaap Kappelle has received speakers honoraria from Bayer and Boehringer Ingelheim. Acknowledgement: The research of Geert Jan Biessels is supported by grant 2010T073 from the Netherlands Heart Foundation. Received: 17 July 2012 Accepted: 24 August 2012 Citation: European Neurological Review, 2012;7(3):169–73 Correspondence: Geert Jan Biessels, Department of Neurology, University Medical Centre Utrecht G03.232, PO Box 85500, 3508 GA Utrecht, The Netherlands. E: g.j.biessels@umcutrecht.nl Diabetes and ischaemic stroke are common conditions that often co-occur. The relationship between diabetes and stroke is bidirectional. On the one hand, people with diabetes have a more than two-fold increased risk of ischaemic stroke compared to people without diabetes. 1 On the other hand, acute stroke can give rise to abnormalities in glucose metabolism, which in turn may affect outcome. 2 In the current review, which is based on a recent paper from our group in the Lancet Neurology, 3 we describe the management of diabetes both in the acute stage of stroke and in the longer term, with regard to secondary prevention. Diabetes and the Risk of Stroke A recent meta-analysis of prospective studies including 530,083 participants reported a hazard ratio for ischaemic stroke of 2.3 (95 % confidence interval [CI] 2.0–2.7) in people with versus people without diabetes. 1 Considering that the estimated world-wide prevalence of diabetes in adults is around 10 %, this implies that one in eight to nine cases of stroke is attributable to diabetes. Diabetes is associated with different aetiological subtypes of ischaemic stroke, including lacunar and athero- and cardioembolic strokes. 4–6 Moreover, the risk of atrial fibrillation, the major cause of thromboembolic stroke, is increased by 40 % in diabetes. 7 Diabetes-associated risk factors for stroke include diabetes-specific factors (e.g. hyperglycaemia) and vascular risk factors (e.g. hypertension, dyslipidaemia), but also genetic, demographic, and lifestyle factors. The contribution of these factors, many of which are strongly interrelated, is likely to differ according to diabetes type and age. © TOUCH BRIEFINGS 2012 Hyperglycaemia and Stroke Outcome Hyperglycaemia occurs in 30–40 % of patients with an acute ischaemic stroke. 2,8 The majority of these patients does not have a known history of diabetes. 2 In a proportion of patients hyperglycaemia reflects pre-existing but unrecognised diabetes, but more often it is due to an acute stress response, commonly named ‘stress hyperglycaemia’. Stress hyperglycaemia is defined as a fasting glucose >6.9 mmol/l or a random glucose >11.1 mmol/l during hospital stay that spontaneously reverts to normal range after discharge. 9 Hence, glucose levels at admission generally do not distinguish between stress hyperglycaemia and diabetes. In this setting, elevated glycated haemoglobin (HbA 1c ) levels (≥6.5 %) can help to identify previously undiagnosed diabetes. 9,10 Patients with ischaemic stroke who are hyperglycaemic at admission are at increased risk of poor outcome. Compared to normoglycaemic patients, patients with hyperglycaemia and a known history of diabetes have an elevated relative risk of in-hospital or 30-day mortality (unadjusted relative risk 2.0 [95 % CI 0.04–90.1]). 2 In those without a history of diabetes this risk is 3.3 (95 % CI 2.3–4.7). 2 The association between hyperglycaemia and poor outcome primarily involves patients with large-vessel infarction. 11 In small-vessel ‘lacunar’ stroke, moderate hyperglycaemia has even been associated with improved outcome. 8 There is still uncertainty whether the association between hyperglycaemia and poor stroke outcome reflects a causal relation. The acute stress response of the body after stroke is a key factor in the development of post-stroke hyperglycaemia and as such it could be argued that hyperglycaemia is just an epiphenomenon, indirectly reflecting stroke severity and the condition of the patient. 169