Section Editors: Marc Fisher, MD, and Kennedy Lees, MD Management of Hyperglycemia in Acute Stroke How, When, and for Whom? Michael T. McCormick, MRCP; Keith W. Muir, MD, FRCP; Christopher S. Gray, MD, FRCP; Matthew R. Walters, MD, FRCP C urrent acute therapies for ischemic stroke are limited. Only a small proportion of stroke patients are eligible to receive fibrinolytic therapy; clinical trials of neuroprotectant drugs have yielded disappointing results, and other potential interventions are at very early stages of development. Against this background, coordinated stroke unit care is, however, of proven benefit; reduced mortality, institutional- ization and dependency. Clinical trials demonstrating the benefit of stroke unit care have recognized the potential but unproven benefits that may be realized through rigorous physiological monitoring and intervention to correct derange- ments in the acute phase. This review will discuss the complex relationship between hyperglycemia and stroke, with particular emphasis on the role of glycemic control in the acute stroke patient. Whether acute hyperglycemia is a cause of neurological deterioration or an epiphenomenon, is a distinction pivotal in management of the stroke patient with hyperglycemia. Post- stroke hyperglycemia is common and, at least in nondiabetic individuals, is associated with a poorer stroke outcome when compared to normoglycemia. 1,2 In a systematic review of observational studies examining the prognostic significance of hyperglycemia in acute stroke, the unadjusted relative risk of in-hospital or 30-day mortality was 3.07 (95% CI, 2.50 to 3.79) in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in those with diabetes. 3 The relative risk of poor functional outcome in hyperglycemic nondiabetic patients was 1.41 (95% CI 1.16 to 1.73). Using MRI it has been demonstrated that in patients with acute perfusion diffusion mismatch within 24 hours of stroke onset, acute hyperglycemia corre- lates with reduced salvage of mismatch tissue from infarction, greater final infarct size, and worse functional outcome. 4 As a consequence, not only has a causal relationship between hyperglycemia and poor outcome been assumed, but also a benefical treatment effect from control of hyperglycemia (as reflected in local, national and international management guidelines). Prospective trial data for such a treatment effect have been lacking and in the absence of randomized trial evidence, clinical practice has been guided by extrapolation of results from nonstroke populations that inform consensus guidelines. 5 The absence of optimal quality evidence in this area has been recognized, and evidence derived from patients with acute stroke is becoming available. Recent data will be reviewed and discussed. Diabetes or Poststroke Hyperglycemia? Stroke is predominantly a disorder of older people in whom the prevalence of previously recognized type 2 diabetes is approximately 7%. Depending on the diagnostic criteria used, a further 7.7 to 14.8% of persons over 65 years of age may have previously unrecognised type 2 diabetes. 6 In any given stroke population the prevalence of diabetes is approximately 8% to 20%, with a further 6% to 42% having evidence of previously unrecognized diabetes before the acute event. 2,7–11 Such estimates are, however, complicated by the high prevalence of poststroke hyperglycemia; in one series of acute stroke patients it was estimated that up to 68% had poststroke hyperglycemia, defined by a plasma glucose concentration 6.0 mmol/L. 2 It is possible that poststroke hyperglycemia is primarily a stress response in relation to stroke size and severity 12 : however, poststroke hyperglycemia is prevalent across all clinical subtypes and severities of stroke and is not restricted to those most severely affected. 10,13 Although some studies have suggested that stress hyperglycemia may occur as a result of neuroendocrine dysregulation in response to insular cortex lesions, 14 this finding has not been replicated by others. 15 It remains unclear whether hyperglycemia arises as an epiphenomenon of stroke in general, as a consequence of specific anatomic involvement, or as a reflection of underly- ing dysglycemia. Received June 18, 2007; final revision received November 8, 2007; accepted November 28, 2007. From the Divisions of Clinical Neurosciences (M.T.M., K.W.M.) and Cardiovascular and Medical Sciences (M.R.W.), University of Glasgow; and the School of Clinical Medical Sciences (C.S.G.), Newcastle University, UK. Correspondence to Matthew R. Walters, University of Glasgow, Division of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK. E-mail m.walters@clinmed.gla.ac.uk (Stroke. 2008;39:2177-2185.) © 2008 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.107.496646 2177 Emerging Therapies by guest on May 13, 2017 http://stroke.ahajournals.org/ Downloaded from