In acute ischemic stroke with hyperglycemia, intensive vs standard glucose control did not improve 90-day outcomes

Several factors, including high rates of reperfusion therapy and early hospital discharge, may explain why this trial found no benefit from intensive glucose control after stroke, according to an ACP Journal Club commentary.

Early intensive glucose control, using continuous IV insulin and a computerized decision support tool to target blood glucose concentration of 80 to 130 mg/dL (4.4 to 7.2 mmol/L), did not improve functional outcomes 90 days after stroke compared to sliding-scale insulin with a target of 80 to 179 mg/dL (4.4 to 9.9 mmol/L). The randomized trial included 1,151 patients, 80% with type 2 diabetes, who had hyperglycemia after an acute ischemic stroke.

The study was published in the July 23/30, 2019, JAMA and summarized in the August 2019 ACP Diabetes Monthly. The following commentary by Mark J. Alberts, MD, was published in the ACP Journal Club section of the Dec. 17, 2019, Annals of Internal Medicine.

Hyperglycemia is seen in many patients with acute ischemic stroke. Although it is associated with worse outcomes, attempts to improve outcomes by treating hyperglycemia have been largely unsuccessful in ischemic stroke and other conditions, such as critical illness. Hyperglycemia can worsen outcomes through a number of processes—however, which ones are most relevant in ischemic stroke is unclear.

The study by Johnston and colleagues was well-designed and well-conducted. Several factors might explain the lack of benefit with intensive therapy. More than 27,000 of 30,000 patients screened did not meet eligibility criteria. The authors indicated that common reasons for exclusion included time delays, blood glucose levels, and NIHSS scores.

Most patients (68%) were treated with reperfusion therapy. Although such treatment is not 100% effective, a relatively high rate of reperfusion might have mitigated effects of high levels of lactate and other toxins produced as a result of hyperglycemia in the setting of ischemic stroke. High rates of early hospital discharge (before completing the 72-h intervention period) in both groups and higher rates of intensive treatment discontinuation (e.g., due to hypoglycemia) might have attenuated benefits in the intensive-therapy group. Although intensive therapy achieved lower blood glucose levels than standard therapy, it may have been too late (6 to 9 h after treatment initiation) to result in overt clinical benefit.

Based on the study by Johnston and colleagues and the current literature, tight, intensive glycemic control in patients with acute ischemic stroke does not seem to be warranted in the acute care period.