Ablation of the Duodenal Mucosa as a Strategy for Glycemic Control in Type 2 Diabetes: Role of Nutrient Signaling or Simple Weight Loss.

Abstract

As our understanding of the pathophysiology of type 2 diabetes (T2D) has advanced, new oral and injectable medications have been developed that target a growing number of the pathophysiological processes that cause hyperglycemia. In addition, weight-loss therapy, involving lifestyle interventions, antiobesity medications, or bariatric surgery, has been demonstrated to be highly effective in T2D management. The expanded number of treatment options has provided an increased capacity for glycemic control. Even so, T2D remains a progressive disease, requiring the intensification of therapy over time, and many patients still do not achieve HbA1c targets. Therefore, new therapeutic strategies for effective and safe glycemic control are critically needed. In this issue of Diabetes Care , Rajagopalan et al. (1) present a new therapeutic strategy for treatment of T2D. The strong point of the study is that the authors have developed and studied a novel therapeutic approach in T2D that could elucidate new disease mechanisms involving the role of the duodenum in metabolic regulation. The authors present a 6-month interim analysis of a phase I, single-arm, nonrandomized cohort study assessing safety and efficacy of endoscopic duodenal mucosal resurfacing (DMR) for treatment of T2D. This is a first-in-human experience with this intervention, which ablates the duodenal mucosa between the ampulla of Vater and the ligament of Treitz in a two-step endoscopic procedure. First, a catheter with a terminal balloon is passed into the duodenum that has three needles spaced at 120° around the balloon’s circumference. The needles are used to inject saline into the submucosal space in order to circumferentially separate and lift the mucosa from underlying tissues in the duodenal wall. A second catheter then introduces another balloon that thermally ablates (i.e., burns) the lifted mucosa at a temperature of ∼90°C (194°F). The conceptual basis of the procedure is derived from observations that …