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      Diabetes Mellitus, Acute Hyperglycemia, and Ischemic Stroke

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      , MD, MS 1 , , , MD 2 , , MD, PhD 2 , , MD 2 , for the UCLA Stroke Investigators
      Current Treatment Options in Neurology
      Current Science Inc.

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          Opinion statement

          Acute brain ischemia is a dynamic process susceptible to multiple modulating factors, such as blood glucose level. During acute ischemic brain injury, hyperglycemia exacerbates multiple deleterious derangements. Timely and sufficient correction of hyperglycemia during acute brain ischemia may limit the brain injury and improve clinical outcomes. The clinical efficacy of such intervention remains to be proven. Although results from animal and clinical observational studies suggest that hyperglycemia during acute brain ischemia may exacerbate the brain injury, there is no evidence from randomized treatment trials that rapid correction of the hyperglycemia improves outcomes. Given the excess effort, cost, and risk involved in rapid and safe correction of hyperglycemia during acute stroke, less aggressive treatments with subcutaneous insulin seem appropriate at this time. Subcutaneous insulin protocols can maintain blood glucose levels below 200 mg/dL a majority of the time in most patients, especially if basal insulin is added. When available, an endocrinology consultant can optimize the acute treatment and help the transition to long-term care. Given the multiple reports linking admission hyperglycemia with symptomatic hemorrhagic conversion of ischemic stroke treated with thrombolytic drugs, it may be best to rapidly lower severe hyperglycemia in such patients. For example, if the admission blood glucose is approximately 300 mg/dL and the patient is a candidate for thrombolytic therapy, consider giving an intravenous bolus of regular insulin 8 units. Somewhat lower or higher insulin doses may be best for lesser or greater hyperglycemia. Such a bolus will start lowering the blood glucose in about 5 min. A temporary continuous intravenous insulin infusion may then be used in most patients to maintain the glucose closer to normal levels (eg, below 180 or 140 mg/dL).

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          Most cited references41

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          Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.

          We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.
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            Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.

            Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity. Animal studies suggest that infarct expansion may be responsible. The influence of persisting hyperglycemia after stroke has not previously been examined. We measured the blood glucose profile after acute ischemic stroke and correlated it with infarct volume changes using T2- and diffusion-weighted MRI. We recruited 25 subjects within 24 hours of ischemic stroke symptoms. Continuous glucose monitoring was performed with a glucose monitoring device (CGMS), and 4-hour capillary glucose levels (BGL) were measured for 72 hours after admission. MRI and clinical assessments were performed at acute (median, 15 hours), subacute (median, 5 days), and outcome (median, 85 days) time points. Mean CGMS glucose and mean BGL glucose correlated with infarct volume change between acute and subacute diffusion-weighted MRI (r>or=0.60, P or=0.53, P or=0.53, P=0.02). Acute and final infarct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose >or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels >or=7 mmol/L were independently associated with increased final infarct volume change. Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.
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              Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).

              Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001). GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.
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                Author and article information

                Contributors
                abruno@mcg.edu
                Journal
                Curr Treat Options Neurol
                Current Treatment Options in Neurology
                Current Science Inc. (New York )
                1092-8480
                1534-3138
                21 August 2010
                21 August 2010
                November 2010
                : 12
                : 6
                : 492-503
                Affiliations
                [1 ]Department of Neurology, Medical College of Georgia, 1120 15th Street, BI3076, Augusta, GA 30912 USA
                [2 ]Department of Neurology, University of California Los Angeles School of Medicine, Los Angeles, CA USA
                Article
                93
                10.1007/s11940-010-0093-6
                2943579
                20848328
                a8820e89-f9c4-458e-a51c-3b483156520a
                © The Author(s) 2010
                History
                Categories
                Cerebrovascular Disorders
                Custom metadata
                © Springer Science+Business Media, LLC 2010

                Neurology
                Neurology

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