Recruitment has begun at 14 out of an expected 40 centers for a monumental study that will determine the best way to treat patients who have early coronary artery disease (CAD) and type 2 diabetes. CAD is the number one killer of people with type 2 diabetes.

Katherine Detre

Known as the Bypass Angioplasty Revascularization Investigation 2D (BARI 2D), the study is comparing the effectiveness of various therapeutic regimens in reducing the number of deaths from CAD among type 2 diabetics. Investigators aim to determine whether aggressive drug therapy is more effective alone or in combination with surgery in reducing mortality in this population.

“The percentage of Americans who have been diagnosed with diabetes has doubled over the last 20 years, and that trend is expected to continue, partially due to the increase in obesity and sedentary lifestyles,” said Katherine Detre, M.D., professor of epidemiology and director of the Epidemiology Data Center at GSPH, and a coprincipal investigator of the study. “The latest figures show that six to 10 percent of American adults ages 45 and older are diagnosed diabetic. However, it is believed that another six to 10 percent of American adults are diabetic, but are unaware of it.”

In type 2 diabetes, the body is unable to properly use insulin, a hormone needed to metabolize simple sugars. Such insulin resistance is a major risk factor for cardiovascular disease.

“Diabetics develop heart disease earlier than do nondiabetics and have lower survival rates,” said David Kelley, M.D., professor of medicine in the Division of Endocrinology and Metabolism, and coprincipal investigator. “Some 90 to 95 percent of the world’s diabetic patients have type 2, and 80 percent of them are overweight. Obesity appears to trigger the onset of this form of the disease.”

With the help of 2,800 volunteer participants, the study will answer two questions that are critical to type 2 diabetic patients with stable coronary artery disease: Under what circumstances is it best to undergo revascularization in addition to drug therapy, and which method of drug therapy is best at controlling glucose?

BARI 2D is a followup to BARI, a study involving patients with more severe CAD. Detre reported on the results of BARI in the April 6, 2000, issue of the New England Journal of Medicine.

BARI 2D participants at each clinical site are randomly assigned to either aggressive drug therapy alone or to a combination treatment consisting of drug therapy and revascularization, either bypass surgery or angioplasty.

Participants are randomized further to either insulin provision or insulin sensitization to determine which method of glucose control is more effective. Insulin provision, which for decades has been the standard of care for type 2 diabetic patients, involves augmenting one’s insulin store through daily injections or oral agents that stimulate insulin production. This method will serve as the control against which a newer strategy —insulin sensitization—will be tested. Insulin sensitization uses drugs such as metformin or rosiglitazone to lessen the body’s resistance to insulin, thus allowing the body to properly use the insulin it normally produces.

All patients will be followed for a minimum of five years to assess mortality, heart attack, stroke, angina, quality of life, and cost of treatment. They will be on strict risk-factor management to control obesity, lipids, and high blood pressure.

“Improving treatment for diabetic patients who have coronary artery disease is a priority in the field of cardiology today,” said Howard Cohen, M.D., associate professor of medicine, associate chief in the Division of Cardiology, director of clinical services, associate director of cardiac catheterization labs, and cardiology principal investigator of the Pittsburgh site. “The BARI 2D study will resolve ongoing questions about when coronary revascularization should be performed, or even if drug therapy without revascularization is the best option.”