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Research Highlights
In diabetes, no added heart benefit from tighter sugar control
Major VA trial included nearly 1,800 veterans at 20 sites; largest study of its kind
July 17, 2008
Two in three people with diabetes die of heart attack,
stroke or other cardiovascular events. But doctors have
been unsure whether there is a direct cause-and-effect link
between high blood sugar and cardiovascular disease.
Now, a major VA study has provided key evidence to help
answer the question. The seven-year VA Diabetes Trial, which
included nearly 1,800 veterans at 20 VA medical centers,
found that intensive control of blood glucose in type 2
diabetes does little to cut the risk of heart disease, compared
to standard treatment. The results were presented at last
month’s annual scientific meeting of the American Diabetes
Association and could have a significant impact in VA’s health
system, where nearly a fifth of patients—some one million
veterans—have type 2 diabetes.
"While we found that intensive treatment of patients with
type 2 diabetes suggested some benefits from glucose control, it
did not reach significance for a reduction in
the primary endpoint—a composite of
specified cardiovascular disease events—in
this population," said study co-chair William
C. Duckworth, MD, director of diabetes
research at the Carl T. Hayden VA Medical
Center in Phoenix and a professor of clinical
medicine at the University of Arizona.
Past studies inconclusive
Past research had yielded mixed findings,
with most clinical trials failing to show a
significant drop in heart attacks, strokes or
other cardiovascular events when blood
sugar levels were well-controlled.
One aim in the VA trial was to reduce, as
much as possible, other cardiovascular risk
factors, such as hypertension, so the
researchers could hone in on the effects of
blood sugar alone. According to study cochair
Carlos Abraira, MD, of the Miami VA
and the University of Miami, the trial was a
huge success in this regard.
"This was a complicated study in which
all of the patients had multiple health
problems, including 40 percent with prior
cardiovascular events,” Abraira said. “Our
first goal was to reduce all other
cardiovascular risk factors in order to
compare outcomes between standard and
intensive blood glucose treatment groups—and we achieved that goal superbly." On
average, participants in both groups were at
or below targets for lipids and blood pressure
within the first two years and maintained
these levels throughout the study.
While the average A1C—a measure of
blood glucose control over the prior two to
three months—was 9.5 percent upon entry
into the trial, the standard group reached
8.4 percent and the intensive group reached
6.9 percent within six months. Below 7
percent is considered normal. Most
participants in both groups received two to
three oral drugs, such as rosiglitazone or
metformin, plus insulin. The intensive treatment
group received higher doses as
needed to further draw down their blood
sugar. There were no increased deaths
associated with any of the drugs used.
Outcomes better than
expected
Duckworth explained that the study
included only patients who had already
failed what he called "simple therapy":
They had unacceptable blood-sugar levels
even on maximum doses of at least one oral
diabetes drug or insulin—or both treatments
combined. The study population was also
high-risk in that some 40 percent had
experienced prior cardiovascular events, 80
percent had high blood pressure, more than
half had high cholesterol or other lipid
abnormalities, and most were obese. The
average age of the volunteers at the study’s
outset was 60. Even so, there were
significantly fewer cardiovascular events in
both study groups than predicted. The
predicted event total for both groups was
between 650 and 700, whereas the actual
number of events that occurred was 494—263 in the standard group and 231 in the
intensive group. The difference between the
two study arms was not statistically
significant.
"We believe this was largely due to the
excellent blood pressure control, lipid
control, improved diet and exercise, and
treatment with aspirin," said Duckworth.
“Both our intensive and control groups
reduced their blood pressure levels to a
mean of 127 over 70, and both improved
lipid control to near or at American
Diabetes Association guidelines."
The take-home message of the study,
said Duckworth, is that high blood sugar by
itself may be more related to diabetes
complications such as nerve, eye and kidney
problems than to so-called "macrovascular"
complications such as heart attack and
stroke. Retinal and kidney problems are
caused by damage to small blood vessels,
which can result from excess blood sugar.
Duckworth noted another lesson from
the trial: "For intensive glucose control to
yield a significant benefit on cardiovascular
risk reduction, you may have to do it early.
If you go into a population that already has
multiple risk factors—or prior
cardiovascular disease—and longstanding
poor glucose control, you cannot expect
benefits from glucose control in the short
term. You can’t expect miracles."
Secondary results from the trial—including findings on retinal, kidney and
nerve complications—will be presented in
September at the European Association for
the Study of Diabetes meeting in Rome.
This article originally appeared in the July/Aug 2008 issue of VA Research Currents.
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