Yanna Lee

A new study from Yale researchers could help prevent recurrent strokes in high-risk patients.

Researchers followed nearly 4,000 insulin-resistant but non-diabetic patients who had already had a stroke — and thus were at risk for a heart attack and recurring strokes — in order to investigate the link between reduced insulin sensitivity and stroke risk. In a double-blind study, researchers randomly assigned one group of patients to take pioglitazone, a drug commonly used to heighten insulin sensitivity in diabetic and pre-diabetic patients. The control group took a placebo. The group that received pioglitazone demonstrated a much lower incidence of stroke than did the control, reducing their relative risk of stroke by about 24 percent. Patients receiving pioglitazone were also at a lower risk for heart attack and Type 2 diabetes, and had improved blood pressure readings.

“Our trial is the first trial to show that targeting insulin resistance can help keep stroke patients healthy,” said Walter Kernan, the study’s first author and a professor at the Yale School of Medicine.

It subsequently became the longest and best-funded study on stroke in recent history, Kernan said. Silvio Inzucchi, medical school professor and study co-author, noted that the study had almost 4,000 participants, and that researchers needed such a large number in order to prove that pioglitazone had a causal relationship with reduced stroke risk.

Pioglitazone is the first new target for preventing stroke in the last two or three decades, Kernan noted. Past efforts to prevent recurring stroke have included reducing patients’ cholesterol levels and blood pressure, as well as administering daily aspirin as a blood thinner to prevent dangerous clots from forming.

Kernan noted that there is a strong association between insulin resistance and risk for stroke and heart attack. Insulin resistance is a very common condition in adults and is one of the main causes of Type 2 diabetes, he said. While reduced insulin sensitivity is also associated with increased risk of stroke, this association is not quite as strong as that of type two diabetes, which increases a patients’ risk of stroke by two- or three-fold.

There are two types of strokes, according to Kernan: hemorrhagic stroke and ischemic stroke. In the first, a blood vessel bursts in the brain, while in the second a clot blocks off blood supply. Both result in tissue damage in the brain, and this damage can range from mild to severe. Ischemic strokes are more common than are hemorrhagic. Of those who suffer an ischemic stroke, about 20 percent will die. Of those who survive, roughly half will be left with some kind of impairment or disability, Kernan noted.

Pioglitazone does have side effects, Inzucchi said. Patients experienced modest weight gain of about five pounds, and many experienced edema, swollen ankles and feet. The most serious side effect was an increase in bone fractures, Inzucchi said.

Kernan said he thought two main branches of future research would come from the study: The study’s results could be applicable to other types of patients — such as those who had not yet had a stroke but who were at risk of having one — and that the study could spur further research into how to maximize pioglitazone’s benefits while minimizing its risks.

According to the National Stroke Association, stroke is the fifth leading cause of death in America.