Intensive insulin may backfire in acute stroke

By Eleanor McDermid

Intensive control of glucose levels in patients with hyperacute stroke may do more harm than good, results of the randomized INSULINFARCT trial suggest.

The researchers found that infarcts expanded more in patients given intravenous insulin treatment than in those given subcutaneous insulin, despite the intensive regimen providing enhanced glucose control.

Charlotte Rosso (Pitié-Salpêtrière Hospital, Paris, France) and co-workers call the results "disappointing," in view of previous data from animal studies indicating that hyperglycemia contributes to infarct growth.

"We have no explanation for this discrepancy between preclinical and clinical data but they clearly indicate the need for a reappraisal of the pathophysiological models of glucose energy metabolism alterations in the early phase of focal cerebral ischemia," the team writes in Stroke.

Intensive insulin treatment (IIT), delivered intravenously from within 6 hours of stroke symptom onset, resulted in excellent glucose control. In all, 95.4% of 87 patients in the IIT group had average insulin levels below 7 mmol/L over the first 24 hours of treatment, compared with 67.4% of 89 patients who received subcutaneous glucose.

Yet the average infarct growth on diffusion-weighted magnetic resonance imaging (DWI) between baseline and days 1-3 was more than twice that in the than IIT glucose group, at 27.9 versus 10.8 cm³, from similar initial volumes of 11.4 and 10.5 cm³, respectively. The time to initial DWI was nonsignificantly shorter in the IIT than the subcutaneous glucose group, at 132 versus 157 minutes.

Patients' longer-term outcomes were unaffected by insulin treatment, however. At 3 months after stroke, 45.6% of each group had good functional outcomes, defined as a modified Rankin Scale score of 0-2. In addition, 15.6% and 10.0% of the IIT and subcutaneous insulin groups died, respectively, and 38.9% and 35.6%, respectively, had a serious adverse event, defined as symptomatic intracerebral hemorrhage, neurologic worsening, and any event that was life-threatening or extended hospital stay.

But the researchers note: "The study was probably underpowered to detect a modest clinical change on the functional outcome although a favorable functional outcome in favor of IIT seems unlikely when considering the negative result found on DWI."

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