Insulin resistance may be associated with stroke risk

October 11, 2010

Insulin resistance, a condition in which insulin produced by the body becomes less effective in reducing blood glucose levels, appears to be associated with an increased risk of stroke in individuals without diabetes, according to a report in the October issue of Archives of Neurology, one of the JAMA/Archives journals.

Insulin resistance originates from several factors, including genetics, a sedentary lifestyle and obesity, according to background information in the article. The condition contributes significantly to the risk of cardiovascular disease, but whether it predicts ischemic stroke (interruption in blood flow to the brain due to a blood clot or another artery blockage) is still a matter of debate.

One widely used tool to estimate insulin sensitivity is the homeostasis model assessment (HOMA), calculated using fasting blood glucose and fasting insulin levels. Tatjana Rundek, M.D., Ph.D., of Miller School of Medicine, University of Miami, and colleagues assessed insulin resistance using HOMA for 1,509 non-diabetic participants in the Northern Manhattan Study, a study assessing stroke risk, incidence and prognosis in a multi-ethnic urban community. Participants were followed for an average of 8.5 years.

During the follow-up period, vascular events occurred in 180 participants, including 46 who had fatal or non-fatal ischemic strokes, 45 who had fatal or non-fatal heart attacks and 121 who died of vascular causes. Individuals in the top one-fourth (quartile) of HOMA index had an increased risk of stroke compared to those in the other three quartiles of the HOMA index. Adjusting for established cardiovascular risk factors--including glucose level, obesity and metabolic syndrome--did not diminish the association. The relationship between insulin resistance and the risk of first stroke was stronger in men than women but did not vary by racial or ethnic group.

Individuals in the top quarter of insulin resistance had a 45 percent greater risk of any type of vascular event. However, insulin resistance was not associated with heart attack or vascular death separately.

"There are several possible reasons for the stronger effect of insulin resistance on the risk of ischemic stroke than of myocardial infarction in the present study compared within other studies," the authors write. It may be because individuals with a history of heart attack were excluded from this study, or because factors associated with insulin resistance--including high blood pressure, high triglyceride levels and low HDL or "good" cholesterol levels--are more significant risk factors for stroke than for heart attack.

"These findings emphasize the need to better characterize individuals at increased risk for ischemic stroke and the potential role of primary preventive therapies targeted at insulin resistance," the authors conclude.

(Arch Neurol. 2010;67[10]:1195-1200. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was supported by the Gilbert Baum Memorial Grant and the Goddess Fund for Stroke Research in Women, by grants from the National Institute of Neurological Disorders and Stroke, by the Kathleen Scott Research Fellowship from the American Heart Association and a grant from the General Clinical Research Center. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Insulin Resistance Can Be Used to Refine Risk Stratification

"The implications of these findings are exciting if insulin resistance can be proven to be a causal risk factor for stroke (rather than a marker of increased risk) because insulin resistance cannot only be measured but also treated," write Graeme J. Hankey, M.D., F.R.C.P., F.R.C.P.(Edin), F.R.A.C.P., of University of Western Australia, Perth, and Tan Ze Feng, M.D., of the First Affiliated Hospital of Jinan University, Guangzhou, China, and both also of Royal Perth Hospital, Perth, Australia, in an accompanying editorial.

"To establish a causal relationship between insulin resistance and stroke, it is necessary to not only show that insulin resistance is an independent, significant risk factor for stroke, as reported by Rundek et al, but also that removing or minimizing exposure to insulin resistance is associated with a reduction in the incidence of stroke," they write.

Clinical trials to establish this relationship are under way, they note. In the meantime, "we can take confidence from the study of Rundek et al that measuring insulin resistance may help refine prognostic estimates of future risk of stroke obtained by means of traditional risk stratification schemes. Although it is premature to widely screen for insulin resistance as a means to prevent stroke, its measurement may have a role in particular cases in which traditional risk stratification schemes suggest that the patient is at intermediate risk of stroke (rather than high or low risk) and in whom an additional finding of insulin resistance may be sufficiently compelling to supplement lifestyle advice with pharmacological interventions to lower stroke risk."

(Arch Neurol. 2010;67[10]:1177-1178. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was supported by a grant from the China Scholarship Council. Please see the article for additional information, including author contributions and affiliations, financial disclosures, funding and support, etc.
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