BB&T Contributing Editor

NEW YORK – The 1st World Congress on Interventional Therapies for Type 2 Diabetes drew 800 attendees from 46 countries. The congress was formed in 2007 and its meeting had 26 endorsing societies. It boasts a faculty of 80 international leaders in surgery, endocrinology and the basic sciences, as well as public health specialists. The presentations were followed by comments from a panel of eight to 10 authorities in the field, and each was called upon to share their views.

A primary aim of the meeting was to create a forum of experts to work closely with health policy makers from the U.S. and around the world to create an agenda of health policy initiatives, prioritize research, and ensure access to approved treatments.

The congress followed the Diabetes Surgery Summit that was held in Rome in March 2007, where international consensus guidelines were established on the clinical use of the surgical treatment of diabetes with a call for prioritizing research in the emerging field of interventional diabetology. An International Diabetes Surgery Task Force was created to promote the recommendations established by the voting experts of the Rome Summit. It is comprised of leading diabetes researchers, clinical trial specialists, surgeons and scientists.

Diabetes surgery and other interventional techniques may prove to be promising therapeutic options for selected patients with Type 2 diabetes. The challenge is foster collaboration by physicians, surgeons, scientists and makers of health policies. Dr. Harold Lebovitz, professor of medicine in the division of endocrinology and metabolism/diabetes at State University of New York Health Sciences Center (Staten Island, New York), appealed to endocrinologists and bariatric surgeons to join in designing multi-center clinical trials with metabolic and clinical outcomes.

Dr. M. Sue Kirkman, vice president, clinical affairs at the American Diabetes Association (Alexandria, Virginia), reported her organization's plans for a future joint meeting with the American Society for Metabolic and Bariatric Surgery (ASMBS; Gainesville, Florida).

Dr. Jesse Roth, a researcher and diabetologist at the Albert Einstein College of Medicine of Yeshiva University (New York), said, "Surgery has arrived like a comet across the firmament of diabetes and obesity. Teams of talented researchers are moving ahead to define the role of surgery in the treatment of both of these scourges."

An estimated 30% of morbidly obese people (BMI of 35 kg/m² or greater) are diabetic. The use of interventional therapy for treating diabetes in these patients is a new field and has attracted a community of researchers.

Dr. Francesco Rubino, the congress director and a director of the Diabetes Surgery Center at New York-Presbyterian Hospital/Weill Cornell Medical College (New York), was the first to demonstrate that gastric bypass surgery can improve Type 2 diabetes through direct anti-diabetic mechanisms and not solely as a result of weight loss in morbidly obese patients.

Based on his research findings, he proposed that a malfunctioning of the upper part of the small bowel could be one of the possible root causes of Type 2 diabetes. Rubino reported on a growing body of evidence which shows that bariatric surgery can dramatically improve Type 2 diabetes, allowing many patients to maintain normal blood glucose and glycosylated hemoglobin levels while discontinuing all diabetes-related medications.

The possibility of achieving complete, long-term and medication-free remission challenges long-held medical theories that consider diabetes as a chronic, progressive and irreversible illness. The lessons learned by studying gastrointestinal surgery for diabetes show that the surgical rerouting of the gastrointestinal anatomy can positively influence diabetes independently of the weight loss

Rubino noted that the alimentary tract is the largest endocrine organ and that there are 100 hormones (peptides) and neural signals in the gastrointestinal tract that regulate glucose metabolism and that the mechanisms which effect this improvement of the diabetic condition after bariatric surgery still need to be understood. "Metabolic surgery is possibly the best promise we have ever had to cure the disease," he said.

Morbid obesity is classified among the various medical disorders that are referred to as the metabolic syndrome and cause an increased risk of developing diabetes and cardiovascular disease. About 15 million Americans are morbidly obese. The American Society of Metabolic and Bariatric Surgery estimates that 205,000 people underwent surgery last year to help them lose 100 or more pounds that they have been unable to shed and keep off any other way.

Dr. Lee Kaplan, director of the Weight Center of Massachusetts General Hospital and Harvard Medical School (both Boston) presented a review of various interventional therapies for obesity and diabetes. It was concluded that laparoscopic gastric banding leads to an improvement in diabetes that can be directly correlated to the reduced weight.

However, the benefit for diabetic patients from gastric and intestinal bypass procedures, the Roux-en-Y gastric bypass being the most popular, is greater than just from the weight loss. The anti-diabetic impact of gastric bypass procedures also was reviewed by Dr. David Cummings of the Division of Metabolism, Endocrinology and Nutrition and deputy director of the Diabetes, Endocrinology Research Unit at the University of Washington (Seattle). Discussion among the panelists led to the recognition that greater understanding is needed of the molecular mechanisms and effects of gastrointestinal surgery which are independent of weight.

Dr. Philip Schauer, director of the Cleveland Clinic Bariatric and Metabolic Institute (Cleveland), chaired a session that provided an update on the efficacy of bariatric surgery in controlling diabetes, hyperlipidemia and hypertension. Two large and recently published studies in the U.S. and Sweden were reviewed and showed that surgery can dramatically reduce mortality of severely obese patients.

One of these studies was published in the New England Journal of Medicine and showed a 90% reduction of diabetes-specific mortality after gastric bypass surgery. The authors believe that the findings have great significance because Type 2 diabetes has serious cardiovascular complications, which potentially lead to mortality. Schauer noted that up to 15% of bariatric surgery patients lose a lot of weight initially, then gain weight back. The difference between a great result and a good result, he said, is aftercare.

Rubino reviewed published reports and provided an update on data from new clinical studies from around the world investigating the efficacy and safety of gastrointestinal surgery to treat patients who are moderately obese or non-obese. A lively discussion ensued among a panel comprised of surgeons and endocrinologists, although there was no consensus of opinion other than more research is needed. One item that was addressed was the need for defining parameters other than BMI for determining the appropriateness of surgical intervention for diabetes for the overweight or non-obese patients.

Dr. Francine Kaufman, a leading researcher on childhood diabetes and head of the Center for Diabetes, Endocrinology and Metabolism at the Children's Hospital at the University of Southern California (Los Angeles), presented data on the growing rate of obesity and diabetes in adolescents which was characterized as being an epidemic. That was followed by a discussion among a panel of pediatricians and diabetes experts. It was concluded that this subject requires more research before a definitive recommendation can be made.

GI Dynamics (Lexington, Massachusetts) has developed the EndoBarrier gastrointestinal liner that is orally inserted by a non-surgical, endoscopic technique. It lines a portion of the small intestine and creates a mechanical bypass of the duodenum and proximal jejunum. It allows food to pass through the device, and allows bile and pancreatic enzymes to travel outside the liner.

The bile and gut hormones travel around the liner without contacting the food, until later in the gut, thus mimicking a gastric bypass and resulting in weight loss and improved glycemic control. It is removed by using a custom retrieval system in a simple endoscopic procedure. This endoluminal gastrointestinal device may prevent nutrients from contacting the upper part of the small bowel, achieving immediate and sustained improvement of diabetes which is independent of weight loss and suggests a direct action on the mechanism of the disease.

Kaplan presented data from a pilot clinical trial which indicates that patients with uncontrolled Type 2 diabetes using the EndoBarrier achieved a statistically significant improvement of glycemic control (measured as HbA1c levels) in just one week, as compared to a sham control.

Of particular note was the immediate improvement that was independent of weight loss, suggesting a direct action on diabetes. This glycemic improvement was sustained throughout the duration of the study and equaled or exceeded the glycemic control produced by pharmaceutical treatments. To date, more than 100 patients have been treated with the EndoBarrier device.

According to Dr. Christopher Sorli, a clinical investigator at the Department of Endocrinology at the Billings Clinic (Billings, Montana), it can take a patient up to two years on aggressive therapies to get the kind of drop in HbA1c that the EndoBarrier can provide in just 30 weeks.

A discussion also was held on gastric and intestinal stimulator devices. Two products stand out in this category. MetaCure (Orangeburg, New York and Mt. Laurel, New Jersey) is in clinical trials in the U.S. on its Tantalus system, an implanted device that is indicated for the treatment of Type 2 diabetes with obesity. The device is implanted under the skin through a minimally invasive laparoscopic procedure that can be performed in an outpatient setting.

The system includes a rechargeable pulse generator with an external, portable charger, bipolar leads and external control and monitoring components for the patient and physician. Electrical stimulation is delivered through the leads to the sero-muscular layer of the stomach. The product is based on gastric contractility modulation technology and is designed to sense naturally occurring electrical activity of the stomach in real time. The device can be non-invasively read by a physician for further tailoring of the treatment parameters to the patient.

The Tantalus system has the CE mark and is currently in post-market studies in Europe, where trials are under way in Austria and Germany for expanded indications. Tantalus works by applying programmed electrical stimulation to the stomach when a person eats. The system monitors the patient's food intake by sensing gastric activity and automatically adapting a treatment schedule based on eating habits. There is minimal patient action required for applying the stimulation for treating Type 2 diabetes as well as the conditions of overweight and hypertension.

An implantable vagal blocking therapy device, called VBLOC, is being developed in a collaborative effort between the Mayo Clinic (Rochester, Minnesota) and EnteroMedics (St. Paul, Minnesota). It is being touted as a safer alternative to bariatric procedures.

VBLOC went through a six-month, open-label trial at medical centers in Australia, Mexico and Norway and weight losses of 15% to 30% were reported. The VBLOC therapy is similar to a heart pacemaker. It uses high-frequency electricity to block the nerve impulses between the brain and the stomach and pancreas. The lead wires are implanted in the abdomen laparoscopically, with electrodes attached to the vagal nerves and the neuroregulator implanted just under the skin.

The VBLOC delivery system can be removed and studies have shown that it does not damage the vagal nerves. The patient flips a switch to activate the VBLOC device so that the blocking signal can influence how much the stomach functions and food is digested following a meal.

The two main corporate sponsors of the congress are also the leading suppliers of surgical devices and instruments. Covidien (North Haven, Connecticut) has launched an educational web site, www.bariatrics4diabetes.com, that focuses on bariatric surgery as a treatment for Type 2 diabetes. The site contains detailed information on bariatric surgery and its impact on diabetes.

Ethicon EndoSurgery (Cincinnati), a subsidiary of Johnson& Johnson (New Brunswick, New Jersey), funded a study on 3,651 severely obese patients that underwent bariatric surgical procedures. Results of the study were reported in the September issue of the American Journal of Managed Care. The patients were matched by age, gender, geography and health status to control subjects that didn't have surgery.

The study concluded that the cost of the surgery, which ranged from $17,000 to $26,000, was offset within two to four years by medical cost savings.

This study may increase pressure on health insurance companies, some of which specifically exclude weight-loss surgery despite evidence of its effectiveness as a treatment not just for obesity, but also for related conditions including diabetes, high blood pressure and sleep apnea.