Hyperglycemia is associated with worse outcomes during a stroke, but aggressive glucose control does not improve stroke outcomes.
Almost half of the acute ischemic stroke patients present with high glucose levels resulting in worse outcomes, and previous studies suggest that hyperglycemia during a stroke magnifies the damage. Current guidelines from the American Heart Association and American Stroke Association recommend a glucose range from 140-180 mg/dL during an acute ischemic stroke. A recent study assessed the safety and efficacy of intensive glucose control in patients with high glucose levels during an acute ischemic stroke.
The Stroke Hyperglycemia Insulin Network Effort (SHINE) included 1151 patients in the randomized trial. Participants had to be enrolled in the study within 12 hours of stroke onset. Patients were considered to have hyperglycemia if they presented with a glucose level greater than 110 mg/dL for those diagnosed with diabetes and greater than or equal to 150 mg/dL in patients without diabetes. Participants were then randomized to receive intensive glucose control with a target of 80-130 mg/dL or standard glucose control with a target of 80-179 mg/dL for a maximum of 72 hours. Treatment success was determined by a global stroke disability scale. Outcomes were measured 90 days after randomization. The primary outcome was the proportion of patients with improved symptoms and secondary outcomes included NIHSS, Barthel Index, and Stroke Specific Quality of Life Score. Mean glucose levels were 118mg/dL in the intensive group and 179 mg/dL in the standard group. Many participants in the study had previous health conditions that made them more likely to have an acute ischemic stroke; 80% had type 2 diabetes, 23% had lacunar strokes, and 50% had mild strokes.
Results indicate similar percentages of favorable outcomes in both groups but a significantly increased risk for hypoglycemia in the intensive group. No significant differences occurred between either group regarding the secondary outcomes. Positive outcomes occurred in 20.5% of patients in the intensive group and 21.6% of patients in the standard group. In the intensive glycemic control group, 11.2 % of patients stopped treatment early due to hypoglycemia and adverse events. Furthermore, severe hypoglycemia was only documented in the intense glycemic control group. Conversely, the standard treatment group only had 3.2% of patients stop early from hypoglycemia and adverse events. Researchers quickly realized that intensive glycemic control was not improving outcomes and was associated with additional risks. Due to these issues, the SHINE trial was stopped earlier than planned to reduce the chance of patient harm from hypoglycemia and adverse events.
Limitations to this study include site-specific practices that may have decreased the generalizability, the patients who received plasminogen activator therapy may have been treated in a facility with a higher level of care, recanalization data was not captured, and the groups did not sample glucose levels with the same frequency. More research is required to understand the mechanism glucose levels play in stroke outcomes, but the evidence is clear that aggressive lowering of glucose levels does not improve clinical outcomes.
- Intensive / aggressive glucose control was not superior to standard glucose control and both treatments had equivalent patient outcomes.
- Intensive / aggressive glucose control is associated with an increased risk of hypoglycemia and adverse effects.
- No significant differences occurred between treatment groups regarding the secondary outcomes
Johnston, K. C., Bruno, A., Pauls, Q., Hall, C. E., Barrett, K. M., Barsan, W., Durkalski-Mauldin, V. L. (2019). Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke. Jama, 322(4), 326. doi:10.1001/jama.2019.9346
Kassey James, Pharm.D.Candidate, LECOM School of Pharmacy