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Surgery and T2DM

Gastric bypass: solution to the resolution of T2DM

Do intestinal hormones hold the key to diabetes resolution?

Why gastric bypass often results in the rapid resolution of type 2 diabetes is one of the crucial questions in bariatric and metabolic surgery. Now, new data from researchers at Lund University may provide some answers, which could result in new treatments for obesity and diabetes.

Dr Nils Wierup

Although some 85% of patients with type 2 diabetes who undergo a gastric bypass procedure show a return to normal blood sugar levels within few days of surgery, long before any weight loss, there have been few clues as to why this happens.

"The data offer insights into how gastric bypass surgery works,” said the study's main author, Dr Nils Wierup, associate professor at Lund. "Most previous studies have analysed samples taken from patients before and after a gastric bypass, but there is a risk that the results are misleading. They may not be attributable to the operation itself, but rather to factors such as weight loss and reduced food intake.”

Study

The study, Effects of ingestion routes on hormonal and metabolic profiles in gastric-bypassed humans, published in the Journal of Clinical Endocrinology & Metabolism, simulated pre-operative digestion and compared how the same patient metabolises nutrients following surgery.

In some gastric bypasses, the surgeon inserts a catheter into the part of the stomach that no longer has contact with food as a precautionary measure. This was what gave the researchers an opportunity to study the exact difference between food intake before and after the procedure.

The participants were given a set amount of a nutritional drink and blood samples were taken before, during and at short intervals after it was ingested. The next step was to inject the same amount of nutritional solution through the catheter over the same length of time as it had taken the patient to drink it and the same samples were taken. The food then ended up where it would have been before the gastric bypass.

In four female patients who had catheters inserted into the bypassed portion of the stomach as part of their post-operative care, researchers analysed the hormones produced when food travelled through the catheter to mimic the pre-operative digestive tract. Researchers compared those findings to the hormonal activity when a meal was digested through the new bypassed route.

They found that patients' levels of plasma insulin increased 4.6-fold (p<0.05) and glucagon-like peptide-1 two fold (p<0.05). There was also a 2.5-fold increase in glucose-dependent insulinotropic peptide (0<0.05) plasma levels, compared with the gastrostomy.

The changes in hormone levels were accompanied by elevated branched-chain amino acid levels (1.4–2-fold, p<0.05) and suppressed fatty acid levels (∼50%, p<0.05) following gastric bypass surgery.

This hormonal activity, particularly spikes in insulin, allowed patients to digest the meal while maintaining better control of their blood sugar.

“When the patient drank the solution, the insulin levels in the blood rose almost five times as much as when it was injected into the closed-off stomach,” said Wierup. “Intestinal hormones, which play a significant role in controlling blood sugar levels, rose sharply, as did certain amino acids. There was also a major impact on blood lipids, with the levels roughly halved.

Conclusion

"We believe these changes are part of the answer to why gastric bypass cures type 2 diabetes. We have looked at just a few intestinal hormones. There may be a hundred or more involved in the body's complex sugar metabolism. 

Dr Jan Hedenbro, one of the surgeons in the study, added: "If we can identify the mechanism behind this, it will open the way for both more individually tailored operations and, in the long run, the possibility of achieving the same results with pills rather than with surgery."

"Unlike past studies that compared digestion before and after surgery, our method eliminated concerns that differences in weight and food intake following the surgery could influence the analysis," said Wierup. "Using this strategy, we were able to prevent confounding factors from affecting the data."

Despite the study's findings that gastric bypass could cause changes in hormones that lead to decreased diabetes symptoms, it did not necessarily prove a cause-and-effect link.

“Surgery is currently the most effective weapon we have to combat morbid obesity and, as a side effect, it has proven to relieve symptoms of type 2 diabetes,” Wierup added. “Exploring the impact this surgery has on digestion could yield new, non-surgical strategies for treating diabetes and obesity.”

Co-authors of the study included Drs A Lindqvist, P Spégel, M Ekelund, H Mulder, L Groop and J Hedenbro, all of Lund University.

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