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.
- INCLUSION CRITERIA:
- Women 30-55 years of age.
- Must give written informed consent prior to entry in the protocol.
- Must fulfill at least 4 of the classification criteria for SLE as defined by the
American College of Rheumatology.
- Diagnosis of SLE made 5 or more years prior to study participation.
- Pregnancy within one year of study participation. Women of childbearing potential are
required to have a negative pregnancy test at screening.
- Previous diagnosis of Type 1 or 2 diabetes mellitus.
- History of cerebrovascular accident (CVA: presence of irreversible or partially
reversible motor and/or sensory deficits of sudden or recent onset on the basis of
vascular occlusion or insufficiency, complete, incomplete or in evolution, persisting
greater than 24 hours or lasting less than 24 hours with an anatomic correlate).
- Previous diagnosis of peripheral vascular disease (PVD: presence of arterial
claudication [pain in the muscles of the upper or lower extremities, induced by
exercise and relieved by rest, with absent pulses and/or confirmed by Doppler flow
studies and/or angiography] lasting greater than 6 months and/or evidence of gangrene
or significant tissue (digit or limb) loss not attributable to Raynaud s phenomenon).
- Therapy with pulse methylprednisolone or pulse prednisone within 4 weeks of study
- Initiation or change in dosage of antilipemic agents within the preceding six weeks.
- Any active viral or bacterial infection
- Significant concurrent medical condition that, in the opinion of the Principal
Investigator, could affect the patient s ability to tolerate or complete the study.
- Clinical coronary artery disease (CAD) defined as: history of MI and/or definite or
classic angina (substernal chest discomfort provoked by exertion or emotion and
relieved by rest or nitroglycerine), and/or conclusive evidence of MI on ECG
- Renal failure defined as hemodialysis-dependant, or calculated GFR less than or equal
to 30 mL/minute (calculated by the MDRD 4 variable formula).