Insulin Resistance Predicts Stroke, Vascular Risk in Nondiabetics

Susan Jeffrey

February 28, 2008

February 28, 2008 — A new analysis from the Northern Manhattan Study suggests that insulin resistance is associated with an increased risk for a first ischemic stroke and combined vascular events in nondiabetics.

Researchers report that insulin resistance, defined in this study as a homeostatic model assessment of insulin sensitivity (HOMA) index of greater than 3, was associated with a more-than-doubled risk for ischemic stroke and a 50% increase in vascular events, including myocardial infarction (MI), stroke, or vascular death, independent of waist circumference, body mass index (BMI), or other components of the metabolic syndrome.

These findings "again raise the issue that it's not just diabetes but may be prediabetes or insulin resistance that we need to detect and possibly treat to reduce the risk of stroke and vascular disease," senior author Ralph Sacco, MD, from the University of Miami Miller School of Medicine, in Florida, told Medscape Neurology & Neurosurgery.

The study was presented here at the American Stroke Association International Stroke Conference 2008. First author on the paper was Tatjana Rundek, MD, also at the University of Miami.

Underlying Mechanism

This group previously reported that metabolic syndrome is associated with an increased risk for stroke and vascular events (Boden-Albala B et al. Stroke. 2008;39:30-35). Insulin resistance is an important underlying mechanism of metabolic syndrome, type 2 diabetes, and cardiovascular disease, the authors write. Insulin resistance may affect up to 40% of healthy subjects, but data linking this prediabetic state and stroke risk are "controversial and limited," they note.

In this study, Dr. Rundek and colleagues used data from the ongoing Northern Manhattan Study to look at this association in 1735 nondiabetic subjects who were free of stroke at baseline. The population's mean age was 68 years, 63% of subjects were women, and it represented a multiethnic cohort: 61% Hispanic, 19% black, and 19% white.

Serum measures of fasting glucose and fasting insulin were used to determine the HOMA index, with insulin resistance defined as a HOMA index of greater than 3.

They used Cox proportional hazard models to determine the effect of insulin resistance on the risk for first ischemic stroke and on combined vascular events, including MI, stroke, and vascular death, adjusting for demographics and traditional vascular risk factors, as well as waist circumference, BMI, physical activity, and alcohol consumption.

The mean HOMA index in this cohort was 2.76 + 7.42. Of the subjects, 25% met the criteria for insulin resistance, with a HOMA index of greater than 3. Over a mean follow-up of 6.9 years, vascular events occurred in 188 subjects, including 38 fatal or nonfatal ischemic strokes, 74 fatal or nonfatal MIs, and a total of 116 deaths from vascular causes.

They found that a HOMA index of greater than 3 was associated with an increased risk for both first ischemic stroke and combined vascular events. "This was true even after controlling for other vascular risk factors such as waist circumference, body mass index, and other components of the metabolic syndrome," Dr. Sacco said.

Risk for Stroke and Combined Vascular Events With HOMA Index > 3 vs < 3

Outcome Adjusted Hazard Ratio 95% CI
First ischemic stroke 2.2 1.2 – 4.0
Combined vascular events 1.5 1.1 – 2.1

Of this population, 63% was Hispanic, Dr. Sacco noted. "We have data that indicate obesity and insulin resistance may be even greater prevalent factors in Hispanics, 1 of the most rapidly growing demographic groups in the United States."

They plan to further examine the relationship between insulin resistance and other markers of stroke risk, including carotid disease, clinically silent strokes, and white-matter disease, he said.

The Northern Manhattan Study is funded by the National Institute of Neurological Disorders and Stroke. The authors report no relevant conflicts of interest.

American Stroke Association International Stroke Conference 2008: Abstract 92. Presented February 21, 2008.

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