Type 2 diabetes may be caused by intestinal dysfunction

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Public release date: 5-Mar-2008

http://www.eurekalert.org/pub_releases/2008-03/nyph-t2d030508.php

Contact: Rodgers

jdr2001@...

New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill

Cornell Medical College

Type 2 diabetes may be caused by intestinal dysfunction

Research in diabetes surgery offers clues to origins of the disease

NEW YORK (March 5, 2008) -- Growing evidence shows that surgery may

effectively cure Type 2 diabetes -- an approach that not only may change

the way the disease is treated, but that introduces a new way of

thinking about diabetes.

A new article -- published in a special supplement to the February issue

of Diabetes Care by a leading expert in the emerging field of diabetes

surgery -- points to the small bowel as the possible site of critical

mechanisms for the development of diabetes.

The study's author, Dr. Francesco Rubino of NewYork-Presbyterian

Hospital/Weill Cornell Medical Center, presents scientific evidence on

the mechanisms of diabetes control after surgery. Clinical studies have

shown that procedures that simply restrict the stomach's size (i.e.,

gastric banding) improve diabetes only by inducing massive weight loss.

By studying diabetes in animals, Dr. Rubino was the first to provide

scientific evidence that gastrointestinal bypass operations involving

rerouting the gastrointestinal tract (i.e., gastric bypass) can cause

diabetes remission independently of any weight loss, and even in

subjects that are not obese.

" By answering the question of how diabetes surgery works, we may be

answering the question of how diabetes itself works, " says Dr. Rubino,

who is a professor in the Department of Surgery at Weill Cornell Medical

College and chief of gastrointestinal metabolic surgery at

NewYork-Presbyterian/Weill Cornell.

Dr. Rubino's prior research has 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.

" When we bypass the duodenum and jejunum, we are bypassing what may be

the source of the problem, " says Dr. Rubino, who is heading up

NewYork-Presbyterian/Weill Cornell's Diabetes Surgery Center.

In fact, it has become increasingly evident that the gastrointestinal

tract plays an important role in energy regulation, and that 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 says.

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 to be seen. Dr.

Rubino proposes an original 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. "

Indeed, in Type 2 diabetes, cells are resistant to the action of insulin

( " insulin resistance " ), while the pancreas is unable to produce enough

insulin to overcome the resistance.

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

(a body mass index, or BMI, of greater than 35kg).

" It has become clear, however, that BMI cut-offs can no longer be used

to determine who is an ideal candidate for surgical treatment of

diabetes, " says Dr. Rubino.

" There is, in fact, growing evidence that diabetes surgery can be

effective even for patients who are only slightly obese or just

overweight. Clinical trials in this field are therefore a priority as

they allow us to compare diabetes surgery to other treatment options in

the attempt to understand when the benefits of surgery outweigh its

risks. Clinical guidelines for diabetes surgery will certainly be

different from those for bariatric surgery, and should not be based only

on BMI levels, " he notes.

" The lesson we have learned with diabetes surgery is that diabetes is

not always a chronic and relentless disease, where the only possible

treatment goal is just the control of hyperglycemia and minimization of

the risk of complications. 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, " adds Dr. Rubino.

Type 2 diabetes, which accounts for 90 to 95 percent of all cases of

diabetes, is a growing epidemic that afflicts more than 200 million

people worldwide.

At a time when diabetes is growing epidemically worldwide, Dr. Rubino

says that finding new treatment strategies is a race against time. " At

this point, missing the opportunity that surgery offers is not an option. "

###

In addition to having performed landmark studies in the field of

diabetes surgery, Dr. Rubino was the principal organizer of an

influential Diabetes Surgery Summit, held in Rome in March 2007. This

international consensus conference helped establish the field, making

international recommendations for the use of surgery and creating an

International Diabetes Surgery Task Force. Dr. Rubino serves as a

founding member.

For more information, patients may call (866) NYP-NEWS.

--

ne Holden, MS, RD

" Ask the Parkinson Dietitian " http://www.parkinson.org/

" Eat well, stay well with Parkinson's disease "

" Parkinson's disease: Guidelines for Medical Nutrition Therapy "

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