A temporary coating that mimics the effects of gastric bypass surgery could help to treat type 2 diabetes
Gastric bypass surgery is a common choice for patients suffering from blood pressure, weight management issues and diabetes. This surgery reverses obesity by making the patient lose huge amount of weight and also helps in management of type 2 diabetes in an independent manner. Because of this successful and well understood surgery, there has been significant improvement in lifestyle and high diabetes remission in the past decades. However, this type of surgery is not the first choice to pursue for many patients because of the risks involved and also because this surgery makes irreversible changes to the gastrointestinal anatomy of the patient. Statistics point out that only 1% to 2% patients who are suitable to have this surgery will every give their nod.
A new pill to “treat” Type 2 diabetes
Researchers at the Brigham and Women’s hospital in Boston and its Centre for Weight Management and Metabolic Surgery collaborated to find a less invasive but still a highly equivalent effective treatment for reversing type 2 diabetes. Such a method could provide same benefits as by gastric bypass surgery and would also be applicable in other areas of therapy. In their work published in Nature Materials they have detailed a preclinical study in which an oral agent was administered in rats whose purpose was to deliver a ‘substance’ which would then neatly coat the rat’s intestine to prevent any contact between dietary nutrients (from meals) and the lining in proximal bowel by acting as a barrier. This coating then helps to prevent any spikes in blood sugar which generally happens after eating meals. The goal was to ultimately have an oral pill which a patient of type 2 diabetes can take before consuming a meal and this temporary coating of the gut could be helpful in somewhat replicating the results of the surgery.
The creation of this kind of oral pill required a collaboration between surgeons and bioengineers who could then develop a suitable material which can be applied in a clinical manner to the patient. When searching for an appropriate material, researchers keep in mind certain properties which are a major requirement. These included having good adhesion properties to be able to adhere or “stick” to the small intestine and the ability to dissolve within few hours as it would only be a temporary coat. After screening potential candidates which were a list of approved and safe compounds, they shortlisted a candidate – a substance called sucralfate. This substance is an approved drug used for treating gastrointestinal ulcers by creating a sticky paste in the acidic environment of the stomach and it binds to the areas of gastric lining wherever required because of current malfunctioning. For their current study, researchers bioengineered this compound into a new material which could coat the intestinal lining as desired and does so without requiring the stomach acid. This novel substance or ‘luminal coating’ labelled LuCI (Luminal Coating of the Intestine) can also be prepared in a dry power form which can be formulated into a pill. In the preclinical trial, LuCI was administered into rats and once it reached the intestine it coated the gut thereby forming a slim barrier as desired. Thus, LuCI creates a barrier emulating the most critical aspect of gastric bypass surgery but in a non-invasive manner than the actual surgery. Normally after consuming meals, blood sugar rises and stays high for some time period. But with this lining is place, the spike was avoided and blood sugar levels were lowered by almost 50 percent within 1 hour of taking LuCI. Obviously, the aim was to have a temporary coat, and once this coating self dissolves within 3 hours, the effect on blood sugar dissipates and the levels returned to normal.
Tests have shown that this coating is safe and it has no adverse effect on the lining of the small intestine making it favourably compatible with the gastrointestinal mucosa. To gain further insights, researchers are currently testing the use of LuCI – both short and long term- on rat models which are obese and have diabetes. They have also done independent tests to show that such LuCI formulations could also be used to deliver therapeutic proteins into the gastrointestinal tract in a similar way. It could be used in nutrient absorption and to protect molecules from getting degraded by the stomach acids and intestinal fluids and degradation by stomach acid and other intestinal fluids. For controlling type 2 diabetes, this pill which could be taken before meal is a tremendous asset for patients.
Yuhan Lee, Tara E. Deelman, Keyue Chen, Dawn S. Y. Lin, Ali Tavakkoli and Jeffrey M. Karp 2018, ‘Therapeutic luminal coating of the intestine’, Nature Materials, DOI: https://doi.org/10.1038/s41563-018-0106-5