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(HealthNewsDigest.com) – A team of researchers, led by a UC Davis veterinary endocrinologist, has shown for the first time that a surgical procedure in rats that is similar to bariatric surgery in humans can delay the onset of type 2 diabetes. The researchers also have identified biochemical changes caused by the surgeries that may be responsible for that delay.
Findings from the study, published online in the journal
Gastroenterology, should help researchers identify strategies for
preventing and treating type 2 diabetes, a chronic condition in which
the body is unable to properly metabolize sugar and fat, leading to
serious complications including heart disease, blindness and kidney
failure.
Type 2 diabetes affects more than 21 million people in the United
States, where it results in more than $150 billion in direct and
indirect annual costs, according to the National Institutes of Health.
“Bariatric surgery currently is considered to be the most effective
long-term treatment for human obesity and often leads to marked
improvements in diabetes,” said the study’s lead author Peter Havel,
a professor with joint appointments in the School of Veterinary
Medicine and Department of Nutrition.
“It has been thought that reduction of blood sugar, which indicates a
reversal of type 2 diabetes, in patients following bariatric surgery
was due to post-surgery weight loss,” Havel said. “This study,
however, supports the observations from a number of earlier clinical
studies reporting that diabetes is often improved prior to
substantial weight loss. It also suggests that endocrine changes in
hormones produced by the gastrointestinal tract may contribute to the
early effects of bariatric surgery, in addition to the later effects
of weight loss.”
“This study confirms our clinical observations that metabolic
regulation — specifically homeostasis of glucose — occurs quickly
after gastric bypass surgery,” said Mohamed Ali, an associate
professor of gastrointestinal surgery and a specialist in bariatric
surgery at UC Davis Health System. “It’s clear from the outcome that
something physiologic is at work with controlling diabetes that is
not related to weight loss.
“UC Davis has the perfect environment for collaboration between basic
and clinical scientists to take this discovery to the next step,
which is identifying the molecular signals that set these physiologic
changes in motion,” said Ali, who was not a participant in this
study, but has collaborated with Havel on previous research.
About bariatric surgery in humans
In severe cases of obesity — usually when the patient is 80 to 100
or more pounds overweight — bariatric surgery is used to alter or
reconstruct the stomach and/or the intestinal tract. In such cases,
obesity is not just a weight issue but also a life-threatening health
problem that often leads to type 2 diabetes, heart disease and sleep
apnea.
There are several types of bariatric surgeries available in the
United States. The most commonly performed surgical procedure, known
as Roux-en-Y gastric bypass surgery, limits the amount of food the
stomach can hold and reroutes the digestive tract, resulting in
changes in intestinal function and hormones produced by the
gastrointestinal tract.
In 2008, about 220,000 people with severe obesity in the U.S. had
bariatric surgery, according to the American Society for Metabolic
and Bariatric Surgery.
The new study
Havel and colleagues set out to test a hypothesis that certain
bariatric surgical procedures were successful in improving type 2
diabetes, at least in part, because the procedures increased the flux
of unabsorbed nutrients to the far end of the small intestine and, in
doing so, triggered increased secretion of two hormones. Those
hormones — glucagon-like peptide-1 (GLP-1) and peptide-YY (PYY) —
are known to have a role in controlling food intake and improving
insulin secretion and insulin sensitivity, thereby helping to
stabilize blood sugar levels.
To test the hypothesis, the researchers carried out a surgical
procedure known as ileal interposition in a line of rats that were
predisposed to obesity and type 2 diabetes. The rat model, developed
in Havel’s laboratory, was known as the UC Davis Type 2 Diabetes
Mellitus (UCD-T2DM) Rat. The pathology of type 2 diabetes in these
animals is more similar to type 2 diabetes in humans than other
existing rodent models of the disease.
The ileal interposition procedure involves relocating a short portion
of the small intestine known as the ileum further forward in the
intestinal tract. Then the researchers compared how long it took for
the animals to develop diabetes, compared with a control group of
rats that had surgery but without rearrangement of the intestines.
They found that the rats receiving the ileal interposition surgery
developed type 2 diabetes 120 days later than did the rats in the
control group. Furthermore, by the time the rats were one year old,
78 percent of the control group rats were diabetic while only 38
percent of the rats that had received the ileal interposition
procedure had developed diabetes.
Havel said the delay in onset of diabetes in the rats would be
similar to delaying the age of onset of diabetes by approximately 10
years in a person, which would be expected to significantly decrease
the amount of time for diabetic complications to develop, and to
reduce the health care costs associated with treating this costly and
prevalent disease.
The researchers also found that, when compared with the control
group, the rats receiving the ileal interposition surgery had:
* lower fluctuations in blood sugar levels;
* improved insulin production, making them better able to
metabolize sugar; and
* decreased levels of lipids (cholesterol and triglyceride) in
the bloodstream, which are known to be risk factors for
cardiovascular disease in humans.
“In addition, results from the study also demonstrated that the ileal
interposition surgery increases production of bile acids, which are
involved in fat metabolism and can increase the production of GLP-1,
the hormone that improves insulin secretion and insulin sensitivity,”
Havel said. “This could contribute to the delay in the onset of type
2 diabetes that we observed in the rats in this study.”
He noted that further studies are needed to better understand how
surgically induced improvements of metabolism can be achieved in
order to discover new methods for preventing and treating type 2
diabetes. Havel, postdoctoral researcher Bethany Cummings and their
colleagues have received funding from a National Institutes of Health
Challenge Grant to continue to pursue research on the effects of
bariatric surgical procedures in the UCD-T2DM model of diabetes.
Collaborating with Havel on this study were Cummings, Kimber
Stanhope, James Graham, Jennifer Lee and Helen Raybould, all at UC
Davis; April Strader of Southern Illinois University School of
Medicine; and Denis Baskin of the Department of Veterans Affairs
Puget Sound Health Care System and the University of Washington,
Seattle.
Funding for the study was provided by UC Davis, the National
Institutes of Health and the American Diabetes Association.
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