Growing evidence shows that surgery on the small bowel may effectively
cure Type 2 diabetes - an approach that
may change the way the disease
is treated. Published in Diabetes Care,
a new study presents scientific evidence that
gastrointestinal bypass
operations involving rerouting the gastrointestinal tract (gastric
bypass) can cause diabetes remission independently of any weight loss,
and even in subjects that are not obese.
The study''s author, Dr. Francesco Rubino of Weill Cornell Medical
Center, explained that prior research had shown that the primary
mechanisms by which gastrointestinal bypass procedures control diabetes
specifically rely on the bypass of the upper small
intestine — the
duodenum and jejunum. This is a key finding that may point to the
origins of diabetes. "By answering the question of how diabetes surgery
works, we may be answering the question of how diabetes itself works.
When we bypass the duodenum and jejunum, we are bypassing what may be
the source of the problem," says Dr. Rubino.
The gastrointestinal tract plays an important role in energy
regulation, and many gut hormones are involved in the regulation of
sugar metabolism. "It should not surprise anyone that surgically
altering the bowel''s anatomy affects the mechanisms that regulate blood
sugar levels, eventually influencing diabetes," Dr. Rubino added.
While other gastrointestinal operations may cure diabetes as an effect
of changes that improve blood sugar levels, Dr. Rubino''s research
findings in animals show that procedures based on a bypass of the upper
intestine may work instead by reversing abnormalities of blood glucose
regulation. In fact, bypass of the upper small intestine does not
improve the ability of the body to regulate blood sugar levels. "When
performed in subjects who are not diabetic, the bypass of the upper
intestine may even impair the mechanisms that regulate blood levels of
glucose," says Dr. Rubino. In striking contrast, when nutrients''
passage is diverted from the upper intestine of diabetic patients,
diabetes resolves.
This, he explains, implies that the upper intestine of diabetic
patients may be the site where an abnormal signal is produced, causing,
or at least favoring, the development of the disease. How exactly the
upper intestine is dysfunctional remains unclear but Dr. Rubino
proposes an explanation known in the scientific community as the
"anti-incretin theory."
Incretins are gastrointestinal hormones, produced in response to the
transit of nutrients, that boost insulin production. Because an excess
of insulin can determine hypoglycemia (extremely low levels of blood
sugar) — a life-threatening condition — Dr. Rubino speculates that the
body has a counter-regulatory mechanism (or "anti-incretin" mechanism),
activated by the same passage of nutrients through the upper intestine.
The latter mechanism would act to decrease both the secretion and the
action of insulin.
"In healthy patients, a correct balance between incretin and
anti-incretin factors maintains normal excursions of sugar levels in
the bloodstream," he explains. "In some individuals, the duodenum and
jejunum may be producing too much of this anti-incretin, thereby
reducing insulin secretion and blocking the action of insulin,
ultimately resulting in Type 2 diabetes." After gastrointestinal bypass
procedures, the exclusion of the upper small intestine from the transit
of nutrients may offset the abnormal production of anti-incretin,
thereby resulting in remission of diabetes.
In order to better understand these mechanisms, and help make the
potential benefits of diabetes surgery more widely available, Dr.
Rubino calls for prioritizing research in diabetes surgery. "Further
research on the exact molecular mechanisms of diabetes, surgical
control of diabetes and the role played by the bowel in the disease may
bring us closer to the cause of diabetes."
Today, most patients with diabetes are not offered a surgical option,
and bariatric surgery is recommended only for those with severe
obesity. But Dr. Rubino believes that BMI cut-offs can no longer be
used to determine who is an ideal candidate for surgical treatment of
diabetes. "There is, in fact, growing evidence that diabetes surgery
can be effective even for patients who are only slightly obese or just
overweight. Gastrointestinal surgery offers the possibility of complete
disease remission. This is a major shift in the way we consider
treatment goals for diabetes. It is unprecedented in the history of the
disease," he concluded.