Insulin Resistance Tied to Stroke Risk in Nondiabetic Patients


NEW ORLEANS — Insulin resistance independently predicted the risk of ischemic stroke and vascular disease in nondiabetic participants in the Northern Manhattan Study, a community-based, prospective cohort of 3,298 people.

The results of the study, which had a mean follow-up of 7.6 years in 1,680 nondiabetic participants with a known homeostasis model assessment for insulin resistance (HOMA-IR) index, suggest a possible role for insulin resistance in the etiology of stroke among nondiabetic individuals, especially men, Dr. Tatjana Rundek reported at the International Stroke Conference 2008.

The results also underscore the need for better characterization of individuals when assessing their risk for stroke and the potential role for preventive therapies targeted at insulin resistance, said Dr. Rundek of the department of neurology at the University of Miami.

Studies have indicated that insulin resistance likely contributes to the atherosclerotic process by creating a proinflammatory state and promoting endothelial dysfunction, she said.

“There have been at least 10–15 case-control studies showing the association between insulin resistance in nondiabetic subjects and cardiovascular risk. One of the more recent prospective studies, the Framingham Offspring Study, showed that in individuals without diabetes, the risk of cardiovascular disease rose in relation to quartiles of the HOMA-IR index.

“However, data on the [relationship between] insulin resistance and risk of stroke [are] pretty controversial and quite limited,” Dr. Rundek said at the conference, which was sponsored by the American Stroke Association.

In the current study, Dr. Rundek and her coinvestigators used the HOMA-IR index to estimate insulin resistance because of the practicality and simplicity of using it in a large, epidemiological study rather than measuring insulin resistance directly via a hyperinsulinemic euglycemic clamp or a fast-sampling intravenous glucose tolerance test.

Of 3,297 individuals in the study who had at least 1 year of follow-up, 1,680 (51%) did not have a history of diabetes or a previous ischemic stroke and had their HOMA-IR index calculated. These 1,680 participants with a mean age of 68 years included 63% women and comprised mostly Hispanic patients (58%), followed by African American (21%) and white patients (21%). Overall, 54% had not graduated from high school and 16% currently smoked.

At baseline, participants with insulin resistance—defined as a HOMA-IR index greater than 3, the 75th percentile for the distribution of the index—were significantly more likely than non-insulin resistant individuals to be Hispanic (68% vs. 55%, respectively), but less likely to be white (15% vs. 23%) or have more than a high school education (39% vs. 48%). Compared with participants without insulin resistance, significantly fewer insulin-resistant individuals drank alcohol in moderate amounts (67% vs. 58%) or were physically active (10% vs. 5%). Insulin-resistant participants also had significantly worse measurements for waist circumference, body mass index, high-density lipoprotein, and fasting blood glucose.

After a mean follow-up period of 7.6 years, 44 patients suffered an ischemic stroke, for an incidence of 3.4/1,000 person-years. Another 61 patients had a myocardial infarction, yielding a rate of 4.7/ 1,000 person-years. A total of 216 patients experienced the combined vascular events outcome of stroke, MI, or vascular death (mostly deaths from stroke and MI), giving an incidence of 17/1,000 person-years.

Insulin resistance was a significant, independent predictor of stroke and a combined outcome of stroke, MI, or vascular death after adjustment for age alone or the full model of socioeconomic and clinical variables (age, sex, race/ethnicity, high school education, waist circumference, systolic and diastolic blood pressure, moderate alcohol consumption, low-density and high-density lipoprotein, and history of smoking and heart disease). Insulin resistance increased the risk of these outcomes by 43%–75%. In analyses stratified by gender or ethnicity, insulin resistance was associated with a significantly higher risk of stroke only among men, but the study had limited power to make comparisons among such subgroups, she said.

“The results support a role for subclinical insulin resistance in the etiology of stroke among nondiabetics,” Dr. Rundek concluded.


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