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T2DM resolution

Small intestine crucial in T2DM resolution post-RYGB

64% of type 2 diabetes was resolved by the intestine

The small intestine changes the way the body processes glucose helping to regulate levels in the rest of the body and helping to resolve type 2 diabetes following gastric bypass surgery, according to a study from researchers at Boston Children's Hospital.

Published in the journal Science, The researchers report that f type 2 diabetes was resolved in 100% of the rats that underwent gastric bypass. Sixty-four percent of type 2 diabetes was resolved by the intestine, and they researchers hypothesise that the other 36% may be due to weight loss or other factors.

Dr Nicholas Stylopoulos

“We have seen type 2 diabetes resolve in humans after gastric bypass, but have never known why,” said the study’s lead author, Dr Nicholas Stylopoulos. “"Previously, we had not considered the intestine as a major glucose-utilising organ. We have found this process is exactly what happens after surgery. People have been focusing on hormones, fat and muscle, but we have shown in this study that the answer lies somewhere in the small intestine most of the time.”

The researchers said that their findings add further evidence to the notion that gastric bypass surgery’s effects stem simply from limiting caloric intake. Their findings could pave the way for future investigations of how to create a medical pathway to mimic the intestine's reprogramming without the surgery.

"With further research, we may find ways to bypass the bypass," said Stylopoulos. "The results of our study are promising because, unlike the brain and other organs, intestines are easily accessible. Furthermore, since cells in the intestine have such a short lifespan, we can easily study and pharmacologically manipulate them to use glucose, without long-term problems.”

Stylopoulos and team injected a radioactive form of glucose into the bloodstream of rats that had undergone bypass surgery. Compared with rats that underwent a sham surgery, rats with gastric bypasses processed nearly twice as much sugar to the intestine, especially to the Roux limb.

When the researchers dissected the animals, they noticed that the Roux limb looked large. In fact, the Roux limb grows to a thickness at least 40% bigger than the intestine of normal rats, said Stylopoulos.

The researchers are trying to figure out why surgery makes the Roux limb get so big. The researchers suspect that undigested food dumped into the intestines from the stomach pouch might somehow trigger the growth.

Moreover, the animals that had undergone a bypass switched their food preferences from eating fatty meals to foods with fewer calories. This is contrary to what was expected, because if the drastically smaller stomach were the main driver of the weight loss, animals should chow down on fatty foods to pack in calories before their pouches get too full.

The ‘new gut section’ increases metabolism and starts producing specific glucose transporter-1 protein, which removes glucose from circulation and utilising it within the organ, stabilising blood glucose levels in the rest of the body.

"Enhancing intestinal glucose uptake and use could offer an opportunity to regulate whole-body glucose disposal and improve glycaemic control in type 2 diabetes," the authors write.

"Exploitation of the changes that occur in intestinal metabolism after [Roux-en-Y gastric bypass] could represent an approach to bypass the bypass, that is, to replace the gastric bypass by equally effective, but less invasive, treatments for obesity-related diabetes," they conclude.

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