EMBARGOED
FOR RELEASE ON
JUNE 7, 2007
APS Contact
Christine Guilfoy
Office: (301) 634-7253
cguilfoy@the-aps.org
Hormone That Signals We Are
Full When Eating Also Curbs Fast Food Consumption And Tendency To Binge Eat
BETHESDA, Md.
(June 7, 2007) — The synthetic form of a hormone previously found to produce
a feeling of fullness when eating and reduce body weight, also may help curb
binge eating and the desire to eat high-fat foods and sweets. The findings
on fast food consumption and binge eating tendencies are based on a 6-week
research study of 88 obese individuals.
The research, entitled “Pramlintide treatment reduces
24-hour caloric intake and meal sizes and improves control of eating in
obese subjects,” appears in the online edition of the American Journal of
Physiology-Endocrinology and Metabolism. Pramlintide is the synthetic
form of amylin, a satiety hormone produced by the beta cells of the
pancreas, which also produce insulin.
“Satiety hormones are commonly thought to control food
intake by signaling to the brain when we are full,” said Christian Weyer,
M.D., the study’s senior author and executive director of clinical research
at Amylin Pharmaceuticals, Inc., in San Diego, Calif. “The findings of our
clinical study further suggest that satiety hormones such as amylin can
exert multiple effects on human eating behavior, such as reduced intake of
highly-palatable foods and reduced binge eating tendency.”
Pramlintide is marketed in the U.S. by Amylin
Pharmaceuticals, under the brand name Symlin, to treat diabetes and control
blood sugar. Amylin is one of several hormones secreted when eating and is
known to work in partnership with insulin to regulate blood sugar.
Pramlintide is also under development as a potential drug for obesity.
The study was carried out in 10 U.S. research sites and
was reported by Steven R. Smith of the Pennington Biomedical Research Center
in Baton Rouge, La.; John E. Blundell of the University of Leeds, United
Kingdom; and Colleen Burns, Cinzia Ellero, Brock E. Schroeder, Nicole C.
Kesty, Kim Chen, Amy E. Halseth, Cameron W. Lush and Christian Weyer, all of
Amylin Pharmaceuticals.
Multi-center, double-blind
study
Eighty eight volunteers, comprised of obese men and
obese post-menopausal women, 25-60 years old, took part in the 6-week study.
(Pre-menopausal females were excluded because estrogen affects hunger and
eating.) Participants were divided into treatment and placebo groups at a
2:1 ratio. Neither participants nor investigators knew which subjects were
receiving placebo and which pramlintide.
Participants began with a four-day inpatient stay. All
subjects received placebo during the first two days. The treatment period
began on day three. The subjects received pramlintide or placebo via
subcutaneous injection 15 minutes prior to each meal: breakfast, lunch and
dinner. They continued their assigned regimen during a 5-week outpatient
period (days 5-41) but reported for brief visits to the research unit on
days 17 and 31. They returned for a final three days as inpatients, ending
the experiment at day 44.
Participants maintained their typical exercise habits
and made no lifestyle changes that could account for weight loss. During the
inpatient stays, food intake was measured throughout the day under carefully
controlled conditions. Participants were allowed to eat as much as they
wanted but were told to eat until they were comfortably full.
On inpatient days 1, 3, and 43, offerings included such
foods as bagels and cream cheese, muffins, cereal, fruit, sandwiches,
casseroles, salads, tortilla chips, potato chips, cookies and soft drinks.
They were also offered an evening snack that included peanut butter
sandwiches and a cookie.
On inpatient days 2, 4, and 44, participants received a
high-fat, high-sugar lunch that included deep-dish pizzas, ice cream and
high fructose corn syrup-sweetened soft drinks. These three meals were the
“fast-food challenge.”
The participants’ 24-hour food intake was measured on
the first day of the experiment, when all were given a placebo, the first
treatment day, (day 3) and on day 43. The participants rated their feelings
of hunger, fullness and nausea throughout these days using a hand-held
electronic device. Participants also completed a 16-item questionnaire on
days 1 and 42 that was designed to measure binge eating tendencies.
The researchers looked at weight, portion size, 24-hour
caloric intake and consumption at a “fast food” challenge.
Weight: Participants who received pramlintide
lost significantly more weight than those who received placebo. This finding
fits with earlier research with rodents and some human studies. The
pramlintide group lost an average of 4.5 pounds, about 2% of total body
weight, while the placebo group remained about the same weight. The
weight loss was in line with a 3.7% weight loss during an earlier 16-week
study, the authors said.
Calories: The pramlintide group ate
significantly fewer calories compared to the first two days of the
experiment, before treatment started. On day 3, the first day of treatment,
the pramlintide group decreased their food intake by 990 calories while the
placebo group decreased caloric intake by a more modest 243 calories. On day
43, the pramlintide group was still ingesting significantly fewer calories
(680 less) compared to what they consumed before treatment began. By
comparison, the placebo group ate only 191 fewer calories on day 43.
Portion control: Within the inpatient setting,
the overall reduction in 24-hour caloric intake with pramlintide was
attributable to subjects eating smaller portions at each major meal. What is
more, the researchers found that the pramlintide group felt just as full and
satiated as the placebo group, even though the pramlintide group was eating
considerably less. This suggests that pramlintide participants did not
experience the increased feeling of hunger and food craving that often
occurs when food intake is reduced with dieting, Weyer said
Fast food intake and binge eating: The
researchers also examined how the hormone affected certain “hedonic” aspects
of eating. Hedonic eating includes, for instance, the consumption of “fast
foods,” that are high in fat or sugar (such as pizza, chocolate and ice
cream), often leading to a sense of reward. The pramlintide group reduced
fast food intake by 385 calories on day 44 during the “fast-food challenge,”
compared to the placebo group, which decreased their intake by 109 calories.
Those taking pramlintide also reduced their scores on a questionnaire
designed to measure binge eating tendencies: On day 42, 83% of participants
on pramlintide were categorized as having “mild-to-none” binge eating
severity, compared to 58% in the placebo group.
These new results are interesting in light of previous
observations in rodents. Rats typically crave high-sugar foods when placed
under stress. When they receive amylin, their stress-induced sugar
consumption significantly decreases. On chronic amylin treatment, obese rats
also exhibit a long-term switch to eating more healthy chow and less
high-fat, high sugar food.
“Our findings illustrate that comprehensive, carefully
conducted clinical studies can provide important new insights into how
hormones help regulate human eating behavior,” Weyer said. Often times, the
food intake effect of hormones in humans is studied only acutely, using a
single meal test.
More natural weight
control?
Unlike many diet pills, which typically block
individual brain chemicals, hormone-based therapies such as pramlintide work
by enhancing existing physiological pathways involved in food intake
control. By developing therapies based on naturally occurring hormones, it
may be possible to help people control how much they eat, reduce binge
eating and resist the drive to overeat even while living in today’s
environment where access to high-caloric food is abundant every day.
While this research is promising, it appears
pramlintide will produce only modest weight loss, probably around 8%, before
reaching a plateau. Amylin Pharmaceutical’s clinical research program in
obesity includes several ongoing studies that test pramlintide in
combination with other hormones involved in weight control, such as peptide
YY and leptin, Weyer said. Research in obese rats suggests that amylin may
restore the response to leptin, which is often lost in obesity. The hope is
that this combination approach will help achieve even greater appetite
control and weight loss.
Editor’s Note: To request an interview with a
member of the research team, please contact Christine Guilfoy at
cguilfoy@the-aps.org or at (301) 634-7253.
***
Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease. The American Physiological Society has been an
integral part of this scientific discovery process since it was established
in 1887.
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