Insulin resistance appears to be associated with a nearly threefold increased risk for ischemic stroke, independently of established cardiovascular risk factors such as diabetes, obesity, and the metabolic syndrome, according to a prospective cohort study reported in the October issue of the Archives of Neurology.
If this conclusion is confirmed in further studies, “insulin resistance may [become] a novel therapeutic target for stroke prevention,” said Dr. Tatjana Rundek of the department of neurology at the University of Miami and her associates.
Although insulin resistance is “a pivotal pathophysiologic contributor” to cardiovascular disease, its role in ischemic stroke “is still a matter of debate,” the investigators noted.
They used data from the Northern Manhattan Study, a prospective, population-based cohort study of stroke, to examine the issue. The study population comprised 1,509 older adults residing in a multiethnic urban community who were enrolled between 1993 and 2001 and followed for a mean of 8.5 years.
The study subjects had no stroke, MI, or diabetes at baseline. The mean age was 68 years. About 60% were Hispanic, 20% were black, and 20% were white.
In all, 23% of the men and 26% of the women were estimated to have insulin resistance, as measured indirectly by the homeostasis model assessment (HOMA).
Overall, 180 subjects had one or more symptomatic vascular events, including 46 ischemic strokes, 45 MIs, and 121 vascular deaths.
Study subjects with insulin resistance – those in the highest quartile of HOMA scores – showed a significant 2.8-fold higher risk of ischemic stroke than did those with lower HOMA scores. This association was stronger in men than in women, and it persisted when the data were adjusted to control for sociodemographic factors, the presence or absence of the metabolic syndrome, and vascular risk factors.
In contrast, neither the association between insulin resistance and MI nor the association between insulin resistance and vascular death were significant, Dr. Rundek and her colleagues said (Arch. Neurol. 2010;67:1195-200).
The findings should not be considered conclusive, since replication “with larger data sets and more end points” is still necessary, they added.
If this association is confirmed, certain classes of drugs that improve insulin sensitivity and beta-cell function may prove helpful in preventing stroke.
The study results also “suggest that metabolic syndrome may not capture all the vascular risk associated with insulin resistance, raising the possibility that other pathways affected by insulin resistance, such as inflammation, may be important,” the researchers said.
Support for the study included the Goddess Fund for Stroke Research in Women, the U.S. National Institute of Neurological Disorders and Stroke, the American Heart Association, and Columbia University. The investigators reported no financial conflicts of interest.