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13 January 2019
By Ali Tavakkoli, MD, Minimally Invasive and Bariatric Surgeon, Chief, Division of General and GI Surgery, Co-Director of the Center for Weight Management and Metabolic Surgery Brigham and Women’s Hospital, Boston, Massachusetts, U.S., Associate Professor of Surgery, Harvard Medical School
The obesity epidemic is driving a parallel epidemic in type 2 diabetes that now affects more than 400 million people worldwide. The prevalence of diabetes is particularly high in the Middle East, where close to 20 per cent of the population has type 2 diabetes. Multiple randomised clinical studies have now shown that bariatric operations, namely sleeve gastrectomy and gastric bypass surgery, are the best available treatment for obese type 2 diabetics, with many patients experiencing diabetes remission and coming off their diabetic medications.
This has created significant interest in the field of metabolic surgery, where surgeries such as gastric bypass (GBP) are performed with a primary focus of helping patients improve their type 2 diabetes.
Despite the clear benefits of surgery — improvement in diabetes, weight loss, reduction in cancer risk, and extended life expectancy — uptake of surgery amongst patients who qualify remains low.
Furthermore, many diabetic patients do not fulfil the current surgical criteria and therefore continue to struggle with their diabetes, a chronic disabling disease that is one of the most common causes of blindness, renal failure, and limb amputation worldwide. There has therefore been significant interest in trying to understand the mechanisms of diabetes resolution after GBP, with the goal of developing less invasive alternatives.
During gastric bypass, the surgeon creates a small pouch at the top of the stomach to reduce the capacity for food intake. The small intestine is then reconstructed, and the new stomach pouch is connected to the lower section of the small intestine. During digestion, food now bypasses most of the stomach and the first part of the intestine, modulating the amount of nutrients, including glucose, and calories that are absorbed. Interestingly, in most patients, the return to normal insulin levels occurs just a few days after surgery, long before significant weight loss takes place.
A team at Brigham and Women’s Hospital (BWH) in Boston, Massachusetts, U.S., has been studying the underlying mechanisms responsible for this rapid improvement in diabetes, with the goal of developing novel drugs, devices, and less invasive surgical procedures that can replicate the metabolic benefits of surgery.
The team, led by the author, in collaboration with Yuhan Lee, PhD, a materials scientist at BWH, and Jeffrey Karp, PhD, a Professor of Medicine at Harvard Medical School and a biomedical engineer and researcher at BWH, recently presented the results of work they’ve done on developing a sticky, gut-coating powder that provides a barrier on the first part of the intestine and mimics the effect of gastric bypass surgery in a non-invasive way. The team hopes that the new compound named LuCI (for Luminal Coating of the Intestine), by delivering medication directly to the upper GI tract, may one day be offered in pill form as an alternative option to surgery.
LuCI is able to coat healthy tissue and form a transient physical barrier on the luminal, or inside, surface of the intestine so that nutrients, including sugar, are not absorbed. Bypassing the upper part of the gastrointestinal (GI) tract appears to be integral to the anti-diabetic effects of gastric bypass surgery. By emulating a critical aspect of bariatric surgery in a non-invasive way, the research team believes that “Surgery in a Pill” could one day be an alternative to an invasive procedure.
As reported in a paper published in the June 2018 issue of the journal Nature Materials, LuCI significantly reduced glucose levels in animals after a meal. One hour after ingesting LuCI, the increase in glucose was lowered by 47 per cent, and this effect completely dissipated within a few hours. Histological analyses showed that the coating had no adverse effect on the lining of the small intestine, and the treatment did not cause the animals to develop diarrhoea or lose weight.
Additional Therapeutic Value
LuCI has also shown promise as a vehicle for site-specific drug delivery to the GI tract. For example, so-called protein drugs are important in the treatment of patients with inflammatory bowel disease, which affects the lining of the lower intestinal tract, or colon, but delivery is challenging. Oral intestinal-targeted protein drugs need protection from the gastric acid and enzymes in the upper GI tract that can degrade these medications. As part of the team’s preclinical animal studies, they tested the ability of LuCI to provide a platform for protein delivery. Using a simple protein, they demonstrated LuCI’s promise in performing this function. These results were published in the June 2018 Nature Materials article previously referenced.
Given the growing diabetes epidemic, there is an urgent need for safe, non-invasive, and effective treatment. Through bioengineering, the team has replicated the anti-diabetic effects seen in patients who undergo gastric bypass surgery, developing a novel approach that can potentially extend this benefit to a much wider patient population. Dozens of medications are available to treat diabetes, but many patients are unable to achieve appropriate blood sugar control while on them. The results with LuCI have been very encouraging. LuCI may prove to be a tremendous asset in treating and improving quality of life for many diabetic patients.
References available on request.