Type 2 Diabetes Mellitus: Metabolic Surgery and Gastric Submucosal Islet Transplantation, Is There a Connection?

Abstract

It was with great interest that we read the article on the role of pancreas transplantation for type 2 diabetes mellitus (T2DM) by Sener et al. (1) in a recent issue of the journal, and we like to contribute two additional points to the discussion. As described in this article, it is already known that after bariatric surgery, obese patients with T2DM have an 80% to 98% probability of having their disease cured. Some recent studies suggest that this is probably related to alterations in the absorption and motility of the upper intestine; however, a precise mechanistic explanation is not yet known, and it is a priority of the scientific community to find it (2). An article by Escalona et al. showed, interestingly, that 24 hr after the implantation of an endoscopic device, glucose values returned to normal in the patients with T2DM of this study. These amazing changes were maintained throughout the follow-up. This device, named endobarrier, covered the pylorus, duodenum, and a small part of the jejunum with an impermeable membrane that prevented the normal absorption of nutrients at these locations, thereby creating, through an unknown pathway, a different method of stimulation and release of hormones of the gastrointestinal system (GI) (3). Not only did this procedure simulate the weight loss found after bariatric surgery but it also cured the patients with T2DM. In a different scenario, using a type 1 diabetes mellitus model, we performed a pilot study of the gastric submucosal space as a site for islet allotransplantation in pigs, with encouraging results (4). Simultaneously, a Polish group has published preliminary results using the same approach, although transplanting unpurified islets, with similar results (5). The main goal of our study was to find a way to prevent the exposure of the islets directly to the blood. This would avoid the induction of a phenomenon known as “instant blood-mediated inflammatory reaction.” This reaction rapidly damages or destroys a large percentage of the transplanted islets. The study also aimed to prevent the low oxygen concentration and high levels of glucose and immunosuppressive drugs in the portal vein circulation that lead to a low survival rate of the intraportally transplanted islets (6). This new site avoids the problems inherent to the portal vein and can also be approached endoscopically. Furthermore, our study found that animals that were no longer receiving insulin treatment became hypoglycemic, showing that a simple change in the way islets received stimulations and released insulin had possibly created a “nesidioblastosis-like syndrome,” as previously characterized by Service et al. (7) in patients with T2DM after bariatric surgery. Despite our current knowledge that the pathophysiology and development of T2DM and type 1 diabetes mellitus are different, there are many consequences that are common to both types, including damage to the neurologic and GI systems and the alteration of the complex interaction of the GI regulatory hormonal system. Taken together with the results of the current body of the literature, a link between the upper intestine absorption of nutrients, GI portal-systemic circulation pattern changes, and the hormonal stimulation and contraregulatory pathways of the GI system is suggested. These insights give us a novel path from which to pioneer an innovative area of research. Gabriel J. Echeverri1,2 1 Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT) Palermo, Italy 2 Division of Abdominal and Transplantation Surgery, Transplantation Unit Fundacion Valle del Lili Cali, Colombia