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Common diabetes drug causes arteries to spasm, endangering heart

The oral medications most widely used to lower blood-sugar levels in patients with type 2 diabetes are likely to increase the risk of spasm of the coronary arteries, reports a University of Chicago-based research team in the July 15 issue of the Journal of Clinical Investigation. Constricted arteries increase blood pressure and decrease blood flow to the heart, causing chest pain and even sudden death, shows the study, which focused on mice with a genetic defect that duplicates the actions of these drugs.

Sulfonylurea drugs are the mainstay of therapy for non-insulin-dependent diabetes, which affects an estimated 15 million people in the United States. These drugs stimulate the beta cells of the pancreas to squeeze out more insulin and also make insulin more effective.

Since the early 1970s, however, several studies have suggested that sulfonylurea drugs may actually increase cardiovascular problems in diabetic patients. The link between these drugs and heart damage has been disputed, because it was not clear -- until now -- exactly how such medications increased cardiovascular risk. The new study demonstrates a direct link between the receptor for sulfonylurea drugs and coronary arterial spasm, heart damage and death.

"This study, even though it involved mice, argues that from now on we should think twice, or maybe more than twice, about using the sulfonylureas, particularly if other options are available," said Elizabeth McNally, M.D., Ph.D., a cardiologist at the University of Chicago and director of the study. She adds that "other options are always available."

The discovery grew out of a laboratory problem. In 1999, William Chutkow, an M.D.-Ph.D. student working in the lab of diabetes specialist Charles Burant at the University of Chicago (Burant is now at U. Michigan), engineered mice lacking the gene for a sulfonylurea receptor known as SUR2. Although these mice initially appeared normal, they tended to die suddenly.
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
1-Jul-2002


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