Endoscopic duodenal hydrothermal ablation for the treatment of type 2 diabetes mellitus

This thesis describes a novel, endoscopic treatment for type 2 diabetes mellitus (T2DM). Despite the availability of a broad array of glucose lowering medications, glucose regulation is still suboptimal in many patients with T2DM and T2DM is a growing worldwide problem. Observations from bariatric surgery point at an important role of the duodenum in metabolic and glycaemic health. Duodenal mucosal resurfacing (DMR) is an endoscopic technique involving hydrothermal duodenal mucosal ablation. After DMR, the duodenal mucosa regenerates and recovers.
This thesis includes the first safety, feasibility, and efficacy evaluations of the endoscopic DMR procedure for the treatment of T2DM. In the first preclinical and clinical studies, we show that DMR is relatively safe and can be performed by experienced endoscopists. In the first multicenter open-label study, HbA1c levels (representing glucose levels over 2-3 months) decrease with maintenance of this effect over at least 2 years. This HbA1c decrease represents the use of one daily glucose lowering drug and can make the difference between using or not using insulin. In the next randomized controlled trial, the effect of DMR was most pronounced in patients with high insulin resistance. In a pilot study, we show that the majority of people with T2DM can discontinue insulin when DMR is combined with GLP-1RA (approved medication for T2DM). After DMR, additional health benefits were observed, such as increased insulin sensitivity, decreased liver fat, improved cholesterol levels, and decreased inflammation. This can point at a broader metabolic effect of DMR.