J-Shaped Association Between Serum Glucose and Functional Outcome in Acute Ischemic Stroke

Abstract

Background and Purpose-Hyperglycemia after stroke is associated with larger infarct volume and poorer functional outcome. In an animal stroke model, the association between serum glucose and infarct volume is described by a U-shaped curve with a nadir Ϸ7 mmol/L. However, a similar curve in human studies was never reported. The objective of the present study is to investigate the association between serum glucose levels and functional outcome in patients with acute ischemic stroke. Methods-We analyzed 1446 consecutive patients with acute ischemic stroke. Serum glucose was measured on admission at the emergency department together with multiple other metabolic, clinical, and radiological parameters. Key Words: acute ischemic stroke Ⅲ functional outcome Ⅲ J-shaped association Ⅲ poststroke hyperglycemia Ⅲ serum glucose H yperglycemia is commonly encountered in patients with acute ischemic stroke, with estimates varying and depending on the frequency of glucose measurements and the criteria used to define hyperglycemia. 1 The incidence of poststroke hyperglycemia is estimated at 45% in studies with frequent glucose measurements and a threshold value of 7 mmol/L to define hyperglycemia. 2 Because the prevalence of previously diagnosed diabetes mellitus in stroke patients is estimated between 10% and 20%, diabetes mellitus is obviously not the only underlying pathophysiologic mechanism of poststroke hyperglycemia. 3 Previously undiagnosed diabetes mellitus and impaired glucose tolerance account for a further 5% to 28%. 3 In addition, 10% to 20% of stroke patients present with hyperglycemia with normal glycosylated hemoglobin. 4 This is considered as a neurohumoral stress response, although studies on the association between serum cortisol and poststroke hyperglycemia yielded conflicting results. 4 Hyperglycemia after stroke is independently associated with infarct volume in magnetic resonance and spectroscopy studies, 5 and poor functional outcome. 6 However, the UK Glucose Insulin in Stroke Trial (GIST-UK) showed no clinical benefit of treating hyperglycemia rapidly with glucose-potassium-insulin infusion. 7 Moreover, mortality was higher in those patients with greatest glucose reductions (Ͼ2 mmol/L), implying a possibly deleterious effect when glucose levels decrease to less than a critical threshold. 7 An animal model study demonstrated that the association between serum glucose and cerebral infarct volume is described by a U-shaped curve with a nadir of approximately 7 mmol/L. 8 However, a similar curve in human studies was never reported.Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.

Predicting Functional Outcome and Symptomatic Intracranial Hemorrhage in Patients With Acute Ischemic Stroke

“…March 2015 The cutoff values used in the age, severity of stroke measured by admission NIH Stroke Scale score, stroke onset to admission time, range of visual fields, acute glucose, and level of consciousness (ASTRAL) score to define hypo-and hyperglycemia were derived from the results of a previous observational study based on the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) 26 ; the IScore uses a threshold of 7.5 mmol/L. 9 In humans, hyperglycemia upregulates the production of thrombin-antithrombin complexes, 27 stimulates the tissue factor production, 28 and decreases the activity of the recombinant tissue plasminogen activator, 29 which impair recanalization.…”

Glucose and Acute Stroke

“…One study reported a J-shaped association between serum glucose and functional outcome and suggested that glucose serum level Ͻ3.7 mmol/L may be associated with poor outcome. 50 However, in this cohort of 1446 patients, only 4 had glucose level Ͻ3.7 mmol/L, suggesting that the results should be interpreted with caution and that spontaneous hypoglycemia is very rare in patients with acute stroke. This is confirmed in the SITS-ISTR register 20 with only 2.3% of the patients with serum glucose level Ͻ4.4 mmol/L.…”

Response to Letter by Fuentes et al Regarding Article, “J-Shaped Association Between Serum Glucose and Functional Outcome in Acute Ischemic Stroke”

“…We thank Fuentes et al for their interest in our work 1 and for their comments. We agree that hypoglycemic values occur only rarely at admission in stroke patients.…”