MONDAY, June 16 (HealthDay News) -- A new study has found a strong association between insulin resistance and peripheral arterial disease (PAD), which leads to a four-to-five times increased risk of heart attack and stroke.

People with the highest levels of insulin resistance (often a precursor to diabetes) had nearly twice as much PAD, regardless of other cardiovascular risk factors such as diabetes. For each quartile of insulin resistance, the risk of PAD increased by about 25 percent.

According to the American Heart Association, PAD involves a narrowing of the arteries leading to the extremities, most notably the legs. It can cause cramping and tiredness in the limbs.

The researchers analyzed data from more than 3,200 adults enrolled in the U.S. National Health and Nutrition Examination Survey 1999-2004. They compared PAD incidence and insulin sensitivity using a model of insulin resistance (HOMA-IR), a test derived from fasting glucose and insulin values.

The overall prevalence of PAD was 5.5 percent. Insulin resistance was independently associated with PAD after the researchers adjusted for age, gender, race/ethnicity, hypertension, hyperlipidemia, smoking, body mass index, chronic kidney disease and blood levels of c-reactive protein, a marker of inflammation.

"We found a roughly 25 percent increase in the risk of PAD for each one-quartile increase in HOMA-IR, a finding that remained consistent despite adjustment for typical atherosclerosis risk factors related to insulin resistance such as body mass index and glycemic [blood sugar] control," study lead author Dr. Reena L. Pande, of the cardiovascular division at Brigham and Women's Hospital in Boston, said in a prepared statement.

"Even after excluding subjects with diabetes, there were graded increases in PAD prevalence with increasing HOMA-IR quartiles, supporting prior observations that PAD is associated with the metabolic syndrome and glucose intolerance, both surrogate markers of insulin resistance.

"Further, the association persisted after adjustment for diabetes or hemoglobin A1c, another measure of blood sugar control, indicating that insulin resistance may play a role in PAD along the entire spectrum of insulin resistance, quite distinct from the impact of diabetes," Pande said.

The study was published in the journal Circulation.

"For doctors and patients, our study highlights the role of insulin resistance in PAD and gives us a snapshot of the association between the two diseases," Pande said. "For this to play out, however, we still need prospective studies that follow over time insulin-resistant patients to determine their risk of developing PAD."

More information

The U.S. National Heart, Lung, and Blood Institute has more about peripheral arterial disease.