Hyperglycaemia, insulin and acute ischaemic stroke

Background: Hyperglycaemia is common in acute stroke and is associated with a poor outcome. Underlying aetiology and mechanism of action is poorly understood. Management remains uncertain. Methods: We undertook a randomised placebo controlled trial to assess the effect of GKI (Glucose-Potassium-Insulin) versus placebo on lesion volume progression and cerebral lactate levels using magnetic resonance imaging (MRI) and spectroscopy (MRS). An observational study of the capillary blood glucose within 48 hours of stroke onset was performed to define the temporal profile of glucose, with a subset followed prospectively to determine the prevalence of abnormal glucose metabolism in patients with stress hyperglycaemia. The association between insular cortex involvement and hyperglycaemia was determined by analysing MRI data sets from two randomised trials. Stroke unit practice for the management of glucose was assessed in a review of the stroke unit trialists’ collaboration data set. Results: • GKI infusion failed to attenuate infarct growth in patients with moderate hyperglycaemia within 24 hours of acute ischaemic stroke. A trend towards attenuation of increased lactate concentration was evident in the GKI treatment arm. Exploratory analyses raised the possibility that GKI may be harmful in patients with persistent arterial occlusion. • Over the 48hour monitoring period 75% of patients developed Hyperglycaemia. Stroke severity was not predictive of admission hyperglycaemia whereas glycosylated haemoglobin was (OR 2.97; 95%CI 1.84-4.78; p<0.001). 50% of patients screened were found to have abnormal glucose metabolism at follow-up. • Insular cortex involvment on MRI was not predictive of admission hyperglycaemia. • Testing for blood glucose concentration in stroke units was infrequent. Of the minority of units that had a protocol in place, the threshold for intervention with insulin was >10mmol/l. Conclusion: We found no evidence that GKI infusion attenuated infarct growth in patients with mild hyperglycaemia following acute ischaemic stroke. In post-hoc analysis the possibility that GKI infusion may be harmful in patients with total occlusion suggests an effect dependent on recanalisation status. A non-significant trend towards attenuation of increased lactate concentration was evident. Stroke severity was not found to be a predictor of post stroke hyperglycaemia. Underlying dysglycaemia was common in non-diabetic patients manifesting hyperglycaemia within 48hours of stroke ictus. Screening of high risk patients with oral glucose tolerance testing is justified and provides a potential opportunity for secondary prevention. Insular cortex involvement did not independently predict hyperglycaemia in acute stroke. Current management of hyperglycaemia is guided by consensus guidelines with little evidence base. Stroke unit practice varies with little change across stroke units over the years.

Level dc:type.qualificationlevel

MD

Grantor dc:publisher.institution

University of Glasgow

Year dc:date.issued

2008

Author dc:creator

• McCormick, Michael Thomas

• R Medicine (General)
• RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Language dc:language

en