Insulin Resistance and Atherosclerosis in Women With Lupus

Overview

This study will test the effects of insulin resistance on atherosclerosis (hardening of the arteries) in women who have systemic lupus erythematosus, more commonly known as lupus. Women with lupus have a higher chance of developing atherosclerosis than the general population, and as a result are more susceptible to heart attack and stroke. Insulin resistance is a particular risk factor for atherosclerosis, and recent small studies have shown that insulin resistance is more common in lupus patients than in those without lupus. The study will consist of a series of tests designed to assess whether there is an association between insulin resistance and atherosclerosis in women with lupus. This research may lead to further studies on possible treatments to reduce the risk of heart disease in lupus patients. Volunteers must be women between 30 and 55 years of age who were diagnosed with lupus within five or more years prior to the study. Volunteers who have kidney failure, diabetes, or existing atherosclerosis will be excluded from the study, as will volunteers who have had pulse steroid therapy within four weeks of the testing or who have been pregnant within one year of the testing. Participants will undergo the following procedures on an outpatient basis: * Blood and urine tests for research purposes. * Electrocardiogram (EKG) to test the general health of the heart. * Oral glucose tolerance test to measure blood glucose and insulin levels. This test is commonly used to diagnose diabetes and pre-diabetic insulin resistance. * Cardiac multidetector computed tomography (MDCT) to determine the amount of calcium present in coronary arteries. This test is used to diagnose atherosclerosis. * Carotid artery ultrasound to show the speed of blood flow through the carotid arteries. This test will show abnormalities and/or blockages in the carotid arteries. * Abdominal ultrasound to determine if the participant has hepatic steatosis ( fatty liver ), which is often found in individuals with insulin resistance and diabetes. * Carotid artery magnetic resonance imaging/angiogram (MRI/MRA) to measure the thickness of blood vessels. This test is used to diagnose atherosclerosis. * Abdominal MRI to estimate abdominal fat. Volunteers may be asked to participate in an MRI/MRA study to evaluate the arteries of the heart. This test is optional and not required by the insulin resistance/atherosclerosis study. The entire series of procedures will require one to three visits to complete.

Women with lupus have a five- to ten-fold increased risk of coronary heart disease compared to the general population. Several decades ago, when women with lupus died shortly after developing the disease, their deaths were attributed to previously undiagnosed and untreated active lupus. But when they died years after their diagnosis of lupus, their deaths were attributed to complications of atherosclerosis (hardening of the arteries). Similar to lupus, atherosclerosis is considered an inflammatory disease. Inflammation plays a major role in atherosclerosis, which results when fatty deposits, cholesterol and other materials accumulate in the blood vessels. The combination of atherosclerosis and lupus greatly increases the risk of cardiovascular disease among women. Research has identified many factors that contribute to the risk of atherosclerosis in people with lupus. These include high blood pressure and abnormal cholesterol levels, chronic inflammation, antibodies that attack proteins that regulate the blood vessels, and some medications used to treat lupus. In the general population, diabetes is an important risk factor for atherosclerosis. A silent condition called insulin resistance can lead to diabetes and has been associated with atherosclerosis in populations that do not have lupus. Recent studies have shown people with lupus are more likely to have insulin resistance than those without the disease.