Drug for Treating Type-2 Diabetes
May Limit Heart Disease Risk
Rosiglitazone, may be a good choice for
patients with type 2-diabetes who require additional
medications to prevent heart attacks.
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 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, presented results from their study at
the annual meeting of the American Diabetes Association.
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.
The study was funded by GlaxoSmithKline, makers
of Avandia (rosiglitazone).
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