ADA: Diet and Exercise Reduces
CVD Risk in Pre-Diabetics
Follow-up analysis of data from the Diabetes Prevention
Program (DPP), showed that diet and exercise can
be more effective than pharmacologic therapy at
warding off cardiovascular disease in patients
with impaired glucose tolerance.
The findings parallel those of the landmark DPP
trial of 3,234 overweight people with pre-diabetes.
Those results, reported last year, showed that
at three years, participants who modified their
lifestyles decreased their risk of developing
type 2 diabetes by 58% compared with those receiving
placebo. The use of metformin also reduced risk,
although not as much: Participants taking the
drug were 31% less likely to develop diabetes
compared with those on placebo.
Now, the new analysis shows that diet and exercise
also reduce indirect measures of heart disease
— especially subclinical inflammation as
indicated by a significant drop in C-reactive
protein (CRP) levels — more than metformin
(P < .05).
Steven M. Haffner, a professor of medicine at
the University of Texas Health Science Center
(UTHSC) in San Antonio, reported the findings
at the American Diabetes Association 63rd Scientific
Sessions. Michael Stern, MD, who moderated the
session, said the new findings are an important
step toward demonstrating that interventions can
prevent not only diabetes, but also its complications.
"DPP showed that we can prevent diabetes,
but we still didn't know if we can prevent the
complications of diabetes, which are what causes
morbidity and mortality," said Dr. Stern,
who is also a professor of medicine at UTHSC-San
Antonio but was not involved with the trial. "Now
we see that interventions do reduce indicators
of cardiovascular disease, though we still have
long-term follow-up planned to confirm if this
translates into actual reduced risk," he
said.
DPP randomized participants to one of three arms.
Participants in the lifestyle intervention group
aimed to lose 7% of their body weight, in part
by lowering their fat intake to less than 25%
of their caloric intake and exercising moderately
30 minutes a day, five days a week. The second
arm received 850 mg of metformin twice a day,
while the third group received placebo. Both the
metformin and placebo groups also received information
on diet and exercise but no counseling efforts.
For the new analysis, the researchers looked at
three markers of cardiovascular disease risk —
CRP, tissue plasminogen activator (TPA), and fibrinogen
— that also have been shown to affect the
risk of developing diabetes, Dr. Haffner said.
Baseline CRP levels were "extraordinarily
high," particularly in women, he said. Noting
that American Heart Association guidelines consider
levels of higher than 3.0 mg/dL to be elevated,
he said that baseline levels in the entire cohort
were 5.9 mg/dL. When broken down by sex, CRP levels
in men and women were 3.2 mg/dL and 7.2 mg/dL,
respectively. From baseline to one year, CRP levels
in men decreased 28% in the lifestyle intervention
group compared with 5% in the metformin group
and 3% in the placebo group, the study showed.
In women, CRP levels decreased 23% in the lifestyle
group, 12% in the metformin group, and 1% in the
placebo group.
TPA levels, which averaged around 11 mg/dL in
both sexes in all three arms at baseline, dropped
18.9%, 15.5%, and 3.0% in the lifestyle, metformin,
and placebo groups, respectively.
And fibrinogen levels, which averaged 380 ng/dL
to 386 ng/dL in the three arms at baseline, decreased
by 1.9% and 1.0% in the lifestyle and metformin
groups, respectively, while increasing by 2.4%
in the placebo group. For all three measures,
lifestyle intervention was associated with a more
significant decrease in values than metformin
(P < .05), Dr. Haffner said.
Seeking to find out why CRP levels dropped so
dramatically among participants on a diet and
exercise program, the researchers used a multiple
linear regression model to look at fasting glucose,
two-hour glucose during an oral glucose tolerance
test, insulin resistance, body mass index (BMI),
waist circumference, and physical activity. The
researchers found that weight loss, as indicated
by a decrease in BMI, was the strongest predictor
of CRP change in both men and women (P,/i>
< .001), Dr. Haffner said. Interestingly, although
maximal weight loss was reached at six months,
CRP continued to decline throughout the one-year
study, he added, suggesting that some other factor
may also be at play.
The next step, he said, is to determine whether
the larger drops in inflammation, fibrinolysis,
and coagulation associated with lifestyle modification
translate into slower progression of atherosclerosis.
A 10-year follow-up study to answer that question
and look at the incidence of other CVD events
in all three groups is now underway. ADA 63rd
Scientific Sessions: Abstract 79-OR. Presented
June 14, 2003.
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DID
YOU KNOW: Type 2 diabetes increases
the risk of cardiovascular disease (CVD) between
two and six-fold and shortens life expectancy
by 5 to 10 years. Once a person with diabetes
has developed severe vascular complications, they
will survive just five years on average. Diabetes
Voice May 2003
