Intensive treatment of hyperglycemia during ischemic stroke did not improve functional recovery

In patients with acute ischemic stroke and hyperglycemia, a target glucose level of 80 to 130 mg/dL was associated with more hypoglycemia and no difference in functional outcomes compared to a target of 80 to 179 mg/dL.


The findings of a recent trial do not support using intensive glucose control to treat hyperglycemia in patients with acute ischemic stroke, with or without type 2 diabetes.

The Stroke Hyperglycemia Insulin Network Effort (SHINE) included adults with hyperglycemia (defined as a glucose concentration of >110 mg/dL [6.1 mmol/L] if the patient had diabetes or ≥150 mg/dL [8.3 mmol/L] if the patient did not have diabetes) and acute ischemic stroke. Patients were enrolled within 12 hours from stroke onset at 63 U.S. sites between April 2012 and August 2018.

Researchers randomized 1,151 patients (mean age, 66 years; 46% women; 80% with type 2 diabetes) to receive intensive treatment (n=581; continuous IV insulin using a computerized decision support tool, with a target blood glucose concentration of 80 to 130 mg/dL [4.4 to 7.2 mmol/L]) or standard treatment (n=570; insulin on a sliding scale administered subcutaneously, with a target of 80 to 179 mg/dL [4.4 to 9.9 mmol/L]) for up to 72 hours. Enrollment was stopped for futility at an interim analysis based on prespecified criteria. Results were published in the July 23/30 JAMA.

During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. The primary efficacy outcome was a favorable outcome at 90 days, which was defined as a modified Rankin Scale score of 0, 1, or 2, depending on baseline stroke severity. Rates of the favorable outcome were similar in the intensive and standard treatment groups (20.5% vs. 21.6%; adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08]; P=0.55; unadjusted risk difference, −0.83% [95% CI, −5.72% to 4.06%]). Intensive insulin treatment also failed to improve secondary 90-day outcomes, which were minimal residual neurological deficits (National Institutes of Health Stroke Scale score), minimal residual limitations in activities of daily living (Barthel Index), or Stroke Specific Quality of Life score.

Intensive treatment was associated with higher rates of hypoglycemia. Treatment was stopped early for hypoglycemia or other adverse events in 65 (11.2%) patients in the intensive treatment group and in 18 (3.2%) patients in the standard treatment group. Severe hypoglycemia occurred in 15 (2.6%) patients receiving intensive treatment and in none receiving standard treatment (risk difference, 2.58%; 95% CI, 1.29% to 3.87%).

Limitations of the trial include the fact that 42% of participants were enrolled by six of the clinical sites, which may reduce generalizability of the results, the study authors noted. They added that the intensive treatment group had slightly more frequent glucose checks (every one to two hours) than the standard treatment group (every three hours), which may have resulted in more reported cases of hypoglycemia in the intensive treatment group.