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New Take On How Gastric Bypass Cures Diabetes

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PET CT images of rats

Caption: This is a PET/CT scan of a rat before (left) and after (right) gastric bypass surgery. This kind of a PET scan shows that after surgery the intestine (the looping structures) are using more glucose, which appear yellow and orange. By comparison the before surgery snapshot (left) reveals that there is very little glucose uptake in the intestines, which are barely visible.
Credit: Courtesy of the Stylopoulos Laboratory

A dramatic, lasting, weight loss treatment for morbidly obese patients is gastric bypass surgery. Although there are many variations of this surgery, each with its signature metabolic pros and cons, the Roux-en-Y bypass is the most popular. The operation involves reducing the stomach size by 90% (which restricts food intake) and reconnecting the remaining stomach pouch to a latter section of the small intestine called the jejunum. Food thus “bypasses” digestion in the stomach and the upper portion of the small intestine. The result of this gastrointestinal re-engineering is that less food is eaten and fewer calories are absorbed in the gut.

Many morbidly obese individuals also have type 2 diabetes.  One of the most intriguing consequences of the surgery is that patients’ blood sugar levels normalize within days—long before any weight loss has occurred. Patients can often stop taking their diabetes medication even before leaving the hospital. Traditionally, doctors recommend weight loss through dieting and exercise to improve blood sugar levels—but this surgery lowers blood sugar levels almost immediately. Why this is, is a mystery—and if we understood the mechanism that might help treat diabetes more effectively in individuals who have not had bypass surgery.

Research by many teams has suggested that reengineering the stomach and intestine changes the balance of hormones and alters gut-mind communication, which then reboots blood sugar control. But now an NIH-funded team at Boston Children’s Hospital has a completely new spin on this phenomenon [1].

After performing the Roux-en-Y bypass in obese, diabetic rats the researchers found that the tissue forming the “Roux” limb (the new passage linking the stomach pouch to the lower gut) seems to grow and expand—an energy intensive process that requires a lot of sugar. The researchers suggest that as the intestinal tissue grows—in girth and absorptive capacity—it harvests glucose from the blood, dropping the sugar level in the blood and essentially curing the diabetes. Once the growth stops the intestine is a larger, energy hungry organ that has to work harder to sustain the increased mass; thus it continuously uses more sugar, which might explain how the effects of the surgery are sustained.

What triggers the growth of this Roux limb? It seems that it’s exposure to the undigested food, which exits the stomach pouch undigested before continuing through the GI tract. Exactly how the Roux-en-Y bypass causes the human intestine to grow in this way still needs much more work to be understood.

Obesity is a major problem in the US and globally. More than two thirds of Americans are overweight or obese. Type 2 diabetes, which affects 26 million Americans, goes hand in hand with obesity [2]. Type 2 diabetes raises the risk of stroke, heart attack, blindness, amputations, kidney failure, nerve damage and a long list of other health problems.

This new research raises the tantalizing possibility of using drugs rather than surgery to reprogram the intestine’s metabolism to remove glucose from the blood and lower sugar levels. Could we learn how to bypass the bypass?

References:

[1] Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Science. 2013 Jul 26;341(6144):406-10.

[2] Overweight and Obesity Statistics

Additional information: Bariatric Surgery for Severe Obesity, National Institute of Diabetes and Digestive and Kidney Diseases, NIH

NIH Funding: National Institute of Diabetes and Digestive and Kidney Diseases