Lifestyle Diseases

Live healthy, or go
under the knife
– Gastric bypass surgery reverses type II diabetes

Several clinical studies published recently have confirmed that gastric bypass surgery can reverse type II diabetes within days after the surgery and before there is any significant weight loss. However, the mechanism by which this happens has remained poorly understood. Now, a French researcher, conducting studies with mice, may have figured out a key part of this mechanism. Callan Emery reports.

The prevalence of type II diabetes in some countries in the Middle East is alarming. Studies in countries such as Qatar and the United Arab Emirates indicate that more than 20% of the local population suffers from the disease. Although genetics is thought to play a role, it is now well accepted that obesity has a key part to play in the development of type II diabetes. This is borne out by recent studies that show that gastric bypass surgery (to treat obesity) also has a dramatic affect on type II diabetes – in some instances completely reversing it just a few days after surgery.

This remarkable outcome was highlighted by Shanu N. Kothari, MD, FACS, director of Minimally Invasive Bariatric Surgery at the Gundersen Lutheran Medical Center in Wisconsin in the US in a presentation to the 25th Annual Meeting of the American Society for Metabolic & Bariatric Surgery (ASMBS) in June this year, where he said that “data continues to support the effectiveness of bariatric surgery in treating type II diabetes in morbidly obese patients.

“Clearly, conventional medical treatment has an important role to play, but surgery should also be presented as an option to appropriate patients,” he urged.

Outlining one of his recent studies Dr Kothari said researchers at Gundersen Lutheran Medical Center had reviewed the levels of hemoglobin A1c in 102 patients with type II diabetes. Half of the patients in the study received conventional medical treatment and the other half had laparoscopic gastric bypass surgery. On average, patients were 48-years-old and had a body mass index (BMI) of 47. In the surgical group, A1c levels dropped by 21% within a year and was maintained for at least three years (the length of the study), while the conventional medical treatment group saw an 11% increase over the same time period. The surgical group saw their A1c levels drop from an average of 7.5 to 5.8 after a year, and to 6.1 after three years while the conventional medical treatment group had an increase in their levels from 7 to 7.8 over the same three years.

Dr Kothari said that most of the surgical patients were able to completely stop diabetes medications. Before surgery, 84.3% were on oral medications and/or insulin. One year after surgery, only 22.4% still required medication. In contrast, the conventional treatment group had an increase in amount of oral medications and/or insulin taken. The study showed the number of patients on diabetes medication grew from 66.7% to 82% in one year.

Lifestyle intervention

These extraordinary results are supported by several other similar studies and various reviews.

Guntram Schernthaner points out in an article in Diabetes Care(1) that lifestyle intervention programmes to treat obesity with diet therapy, behaviour modification, exercise programmes and pharmacotherapy are widely used in various combinations, but unfortunately, with extremely rare exceptions, only result in very modest and transient clinically significant weight loss, particularly in patients with severe obesity.

Discussing gastric surgery to treat obesity Schernthaner refers to the Swedish Obesity Study (SOS)(2), which shows the mean changes in weight and risk factors are more favourable among the subjects treated by gastric bypass than among those treated by banding or vertical banded gastroplasty.

He says that outcomes after surgically induced weight loss published over the past few years are impressive. In a metaanalysis of 22,094 patients (mean age 47 years, mean BMI 46.9, 72.6% women), the mean percentage of excess weight loss was 61.2% for all patients. Excessive weight loss was higher for patients who underwent gastric bypass (61.6%) or gastroplasty (68.2%) compared with those who received gastric
banding (47.5%).

Diabetes reversal

Importantly, he notes that in patients with that had gastric bypass diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% of patients, and hypertension was resolved in 61.7% and resolved and improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients.

This is all very good news, but how and why does this happen?

Schernthaner makes this very point when he remarks that although the evidence for gastric bypass reversing diabetes is now very strong, the mechanism by which this happens is not well understood.

Step in French researcher Gilles Mithieux of Institut National de la Sante et de la Recherche Medicale.

The mechanism

In the September 2008 issue of Cell Metabolism(3) Mithieux published his ground-breaking findings which are set to open up a new understanding of the mechanism by which type II diabetes is reversed by gastric bypass surgery.

Mithieux explains that in addition to removing about two-thirds of the stomach, gastric bypass in effect produces a “double intestine”. The portion closest to the stomach is taken out of the loop so that it receives no nutrients. The segment normally farther down is then attached directly to the stomach, where it receives all the nutrients directly.

He says that in his studies on mice he has shown that these changes in the intestine are key to reversing type II diabetes.

He says that observations show that placing the distal parts of the intestine in a position close to the site of high nutrient availability (the stomach) has the effect of inducing their redifferentiation into a “duodenal”-like intestine involved in the absorption of nutrients.

In addition he notes: “It has become clear that the intestine is more than a digestive tract. The small intestine can produce glucose and release it into the portal blood in a process called intestinal gluconeogenesis. The potential importance of this previously unknown intestinal function has been pointed out by numerous recent studies.”

In other words by placing the lower small intestine, which doesn’t normally produce much glucose, in close proximity to the stomach, it starts to act more like the upper portion.

Another effect of the gastric bypass, he notes, is a decrease in the production of glucose by the liver (which accounts for a much greater overall proportion of blood sugar synthesis). This happens via a GLUT-2 (glucose transporter) metabolic pathway which stimulates the hepatoportal glucose sensor. Put simply, the glucose production by the intestine lowers glucose production by the liver.

Further evidence for the mechanism involved came from studies of mice lacking GLUT- 2. Gastric bypass lost its insulinsensitising benefits in GLUT-2- deficient mice. Similarly, mice whose portal veins had been stripped of their nerve supply also stopped responding to the surgical procedure.

Mithieux says this has led his team of researchers to consider the attractive hypothesis that the RYGBP (Roux-en-Y gastric bypass) procedure may cause increased intestinal gluconeogenesis, which, in turn, quickly modifies the insulin sensitivity of hepatic glucose production and food intake independently of body weight loss and restores glucose homeostasis.

“The new findings support the notion that gastric bypass may be an effective treatment for diabetes in obese patients. It might even have potential for people who are diabetic, whether they are obese or not,” Mithieux concludes.


(1) Schernthaner, Guntram - Bariatric Surgery in Patients With Morbid Obesity and Type 2 Diabetes - Diabetes Care 31:S297-S302, 2008. DOI: 10.2337/dc08-s270
(2) Sjöstrom L, et al - Swedish Obese Subjects Study Scientific Group: Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. - New England Journal of Medicine 351:2683–2693, 2004
(3) Gilles Mithieux et al - Intestinal Gluconeogenesis Is a Key Factor for Early Metabolic Changes after Gastric Bypass but Not after Gastric Lap-Band in Mice - Cell Metabolism, Vol 8, 201-211, 03 Sept 2008.

ate of upload: 16th November 2008

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