June 18, 2003 STANFORD, Calif. - A drug used to treat high blood sugar in people with type-2 diabetes also may lower the risk of cardiovascular disease, according to research at Stanford University Medical Center. If larger studies confirm these results, the drug, called rosiglitazone, may be a good choice for patients with type 2-diabetes who require additional medications to prevent heart attacks.
"If you have a diabetes drug that lowers not only blood sugar but also the risk for heart disease, that might be favorable for the patient with diabetes who already takes as many as eight to 12 pills a day," said James W. Chu, MD, director of the Diabetes Center at Santa Clara Valley Medical Center and adjunct clinical investigator at Stanford. Chu and Gerald Reaven, MD, emeritus professor of medicine at the Stanford School of Medicine, will present results from their study June 17 at the annual meeting of the American Diabetes Association in New Orleans.
In type-2 diabetes, the body's tissues are resistant to or don't efficiently respond to insulin's signal to take up sugar from the blood. If the body doesn't overcome this resistance by making extra insulin, blood sugar will rise, leading to diabetes. First described by Reaven, insulin resistance goes hand-in-hand with a group of health problems including obesity, high blood pressure, type-2 diabetes, increased inflammation and heart disease.
To control blood sugar, people with type-2 diabetes take drugs such as rosiglitazone. But as a result of insulin resistance, they are also at risk of heart attacks, requiring additional medications to treat high blood pressure and cholesterol and to prevent arteries from clogging.
Recent studies have suggested that increased inflammation linked to insulin resistance may contribute to an elevated risk of heart disease. "Theoretically, giving a drug that inhibits the inflammatory response might be useful for preventing cardiovascular disease," Reaven said. Based on earlier work showing that rosiglitazone decreases insulin resistance and lowers blood sugar, Chu and Reaven proposed that the drug also may reduce inflammation.
They tested this idea by giving rosiglitazone to 29 people, 14 of whom had type-2 diabetes and 15 who were insulin-resistant but didn't have diabetes. They followed the participants, recording levels of insulin, blood sugar and other blood components that indicate abnormal metabolism or increased risk for heart disease.
After three months of taking rosiglitazone, the study participants had significantly lower levels of certain molecules that indicate the presence of inflammation. Of these molecules, C-reactive protein is a powerful predictor of cardiovascular risk. The other molecules - plasminogen activator inhibitor-1, E-selectin, L-selectin and P-selectin - are often elevated in people with metabolic and cardiovascular disease.
The finding that these inflammatory molecules decreased in patients taking rosiglitazone hints that the drug also may lower the risk of heart disease, but Reaven urges caution in interpreting these results.
"The fact that the phenomenon takes place doesn't mean the end point will change. You still need a much larger study that measures cardiovascular disease in people taking the drug," Reaven said. He also noted that people who are insulin-resistant but do not yet have diabetes should take diabetes medications such as rosiglitazone only as participants in medical research.
Chu said this study could help doctors decide how to distinguish between the five classes of oral diabetes drugs currently available for type-2 diabetes. "Because most people with diabetes die of heart disease, a drug that potentially can treat multiple facets of the insulin-resistance syndrome is exciting," Chu said.
Other Stanford researchers who contributed to the study include Fahim Abbasi, MD, research associate; Cynthia Lamendola, research coordinator; Tracey McLaughlin, MD, clinical instructor; and Philip Tsao, MD, assistant professor of medicine.
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