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Treatment of Hyperglycemia in Patients with Acute Ischemic Stroke

Jan 14, 2020
Editor: Steve Freed, R.PH., CDE

Author: Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy

SHINE study assesses outcomes of aggressive vs standard blood glucose treatments.

Hyperglycemia can lead to worse clinical outcomes in patients who have had an acute ischemic stroke. Ischemic injury is augmented by endothelial dysfunction, increased oxidative stress, and impaired fibrinolysis. Previous studies were done to assess intensive glucose control. However, these studies were limited in size or did not adequately differentiate in glucose control between groups. American Heart Association/ American Stroke Association guidelines suggest treating glucose levels to the range of 140 to 180 mg/dL. The SHINE study wanted to assess functional outcomes among patients with acute ischemic stroke after receiving intensive blood glucose treatment or standard blood glucose treatment.

The SHINE study was a randomized clinical trial with blinded outcome assessment. Patients that presented with hyperglycemia, acute ischemic stroke, and a National Institutes of Health Institutes of Health Stroke Scale (NIHSS) score of 3-22 presenting within 12 hours from stroke onset were eligible for the enrollment period. Randomization occurred in 1151 patients with a mean age of 66 years old, 46% women, 80% with diabetes; 23% had a lacunar stroke and 50% had mild strokes; 29% were black, 15% were Hispanic. The baseline median glucose level was 188 mg/dL. Patients with type 2 diabetes were hyperglycemic if their glucose level was greater than 110 mg/dL. Patients with no known diabetes diagnosis were considered hyperglycemic if their blood glucose levels were higher than 150 mg/dL. A modified Rankin scale was used to assess the functionality of patients. Those with mild stroke (NIHSS 3-7) had to have a pre-stroke score of 0 (no symptoms) while patients with moderate/severe stroke (NIHSS 8-22) had to have a pre-stroke score of 0 or 1 with 6 being death. The randomization was balanced based on baseline stroke severity. Patients in the intensive treatment group received a continuous intravenous insulin infusion as needed to maintain a blood glucose concentration of 80 to 130 mg/dL. Rapid-acting subcutaneous insulin was given 20 minutes after starting to eat depending on the number of carbohydrates consumed. 

Patients in the standard treatment group received subcutaneous sliding scale insulin every 6 hours as needed to maintain blood glucose of 80 to 179 mg/dL. If blood glucose did not reach the target after 24 to 48 hours, the dose was increased, and long-acting basal insulin was also used. Intensive treatment groups’ blood glucose was checked every 1 to 2 hours vs. 3 hours in the standard treatment group. The treatment was completed in 68 hours from randomization, has passed, death has occurred, or hospital discharge. Enrolling investigators and treatment team was not blinded to treatment assignment. A blinded assessor contacted each patient by telephone at six weeks (+/- 14 days) and evaluated each patient in person at 90 days (+/- 30 days or -14 days) or by telephone if it wasn’t feasible. 

Primary efficacy outcome was the proportion of patients with a modified Rankin scale of score 0 in the mild stroke group, a score of 0-1 in the moderate stroke group, a score of 0-2 in patients in the severe stroke group 90 days after randomization. The secondary outcomes included 90-day NIHSS score, 90-day Barthel Index score, and a 90-day Stroke Specific Quality of Life score with higher scores indicating greater ability to perform daily living activities and better quality of life. The primary safety outcome was severe hypoglycemia (less than 40 mg/dL) during the treatment. A generalized linear model with a log link was used to assess primary analysis. Secondary efficacy outcomes were assessed by the chi square test and Wilcoxon Rank Sum test. Post hoc analysis was conducted to account for multiple comparisons and interpretations of secondary endpoints being exploratory.

A favorable outcome occurred in 20.5% in the intensive treatment group and 21. 6% in the standard treatment group (adjusted RR, 0.97 [95% CI,0.87, 1.08]). Secondary outcomes post hoc analyses of primary outcomes and secondary outcomes did not show a significant difference. Severe hypoglycemia occurred in 2.6% in the intensive treatment group and 0 patients in the standard treatment group (2.58% [95% CI, 1.29%,3.87%]). The difference in death was not statistically significant. Neurological decompensation was higher in the standard treatment group (17 patients vs. 7) which was deemed to be unrelated to treatment.

According to this study, intensive treatment did not improve functional outcomes. Some limitations of this study included the variation in blood glucose checks between the intensive treatment groups, which had checks every 1 to 2 hours versus the standard treatment group which was 3 hours. This study supported the standard treatment of blood glucose.

Practice Pearls:

  • Intensive treatment of blood glucose, which is to keep it in the range of 80 to 130 milligrams per deciliter, did not improve functional outcomes.
  • More episodes of hypoglycemia occurred in patients who underwent intensive glucose treatment versus standard glucose treatment, which was 80 to 179 milligrams per deciliter.
  • Death has occurred in both groups; however, the difference was not statistically significant.

Johnston, Karen C., et al. “Intensive vs. Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke.” Jama, vol. 322, no. 4, 2019, p. 326

Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy



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