Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Keywords:
Duodenal mucosal resurfacing, Type 2 diabetes, Minimally invasive surgery

Type 2 diabetes is a pandemic disease. There are approximately 415 million adults with type 2 diabetes and their number is expected to rise up to 642 million in 2020 [1].

Despite a wide choice of pharmacological medications, many patients do not achieve adequate control of hyperglycaemia [2]. Furthermore, most of the available pharmaceutical approaches do not adequately address the underlying pathophysiological defects, particularly insulin resistance. The hypothesis of insulin resistance improvement has been established from bariatric surgical experience. Indeed, procedures that prevent contact between the duodenal mucosa, bile, and nutrients improve insulin sensitivity [3] and ß-cell function [4]. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has important consequences on glucose homoeostasis [5, 6]. Therefore, on the basis of these pathophysiological considerations, duodenal mucosal resurfacing (DMR) was studied in type 2 diabetes patients. DMR is a novel, minimally invasive, transoral procedure involving hydrothermal ablation to modify the lining of the duodenum. Recently, an initial study in patients with type 2 diabetes [7] assessed safety and glycaemic indices at 6 months; there was an HbA1c improvement of 1.2% at the end of follow-up. Another recent publication showed that both glycaemic markers and transaminase levels were improved after this procedure, suggesting potential favourable effects on fatty liver disease as well [8].

We describe the case of a 44-year-old, overweight (BMI = 28) man with type 2 diabetes treated with oral hypoglycaemic agents (Video 1). Diabetes was insufficiently controlled (HbA1c: 8.2%). The patient was considered for DMR.

Video 1

Hydrothermal duodenal mucosal resurfacing. An investigational, catheter-based, upper endoscopic treatment for type 2 diabetes. Live case presented during the 35th GEEW 2017, Brussels, Belgium.

Video 1

Hydrothermal duodenal mucosal resurfacing. An investigational, catheter-based, upper endoscopic treatment for type 2 diabetes. Live case presented during the 35th GEEW 2017, Brussels, Belgium.

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The procedure was conducted under general anaesthesia and in left lateral decubitus position. The DMR device (RevitaTM System; Fractyl Laboratories Inc., Lexington, MA, USA) is composed of a novel, single-use catheter (Fig. 1) serving for submucosal expansion and hot fluid ablation. The catheter consists of three saline delivery needles affixed to catheters around a balloon. This is connected to the console via a tubing set.

Fig. 1.
Fig. 1. The second-generation RevitaTM Catheter. DMR, duodenal mucosal resurfacing.
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The second-generation RevitaTM Catheter. DMR, duodenal mucosal resurfacing.

Fig. 1.
Fig. 1. The second-generation RevitaTM Catheter. DMR, duodenal mucosal resurfacing.
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The second-generation RevitaTM Catheter. DMR, duodenal mucosal resurfacing.

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Under fluoroscopic visualization, a guidewire was introduced past the Treitz ligament to assist in delivering the catheter. A haemoclip had previously been placed on the opposite site of the papilla to allow verification of the position and to prevent any damage. The balloon was inflated in order to allow the application of an injection needle against the mucosa.

Under endoscopic visualization (using a PCF colonoscope; Olympus), a circumferential submucosal expansion was performed with more than 200 mL of 0.9% saline solution and methylene blue from the genu inferius to the Treitz ligament. The same balloon catheter delivered a hot fluid (86°C; 10 s application with pre- and post-cooling) in order to achieve circumferential thermal ablation limited to the mucosa. Five longitudinally separated ab-lations along the length of the postpapillary duodenum were performed. The sequence included 2 submucosal injections, followed by 1 ablation and repeated 5 times proximally to distally.

The catheter was then withdrawn and the necrosis of the superficial layer of the duodenal mucosa was visually inspected before withdrawing the endoscope.

The patient was discharged the same day with a progressive dietary prescription (liquids to pureed foods at first, and then soft foods) for 2 weeks and proton pump inhibitors for a duration of 1 month.

Three months after the procedure, the patient’s glycated haemoglobin, or HbA1c, fell by 1.2%, from 8.2% at screening to 7.0%. Fasting plasma glucose dropped by 4.1 mmol/L, from 14.5 to 10.4 mmol/L. The alanine transaminase levels remained within the normal range.

DMR is a safe and minimally invasive technique compared to bariatric surgery, which might be an alternative treatment for patients with type 2 diabetes. Further studies, and particularly large controlled trials, are needed to determine the role of this procedure in the treatment of type 2 diabetes, the management of metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, and its durability.

We would like to thank the team for its work during the 35th GEEW 2017, and specifically the medical doctors, foreign experts, nurses, and administrative assistants.

The patient has given informed written consent to undergo this procedure and was part of an ongoing multicentre study approved by our ethics committee.

The device for this study was provided by Fractyl Laboratories Inc.

1.
International Diabetes Federation: IDF Diabetes Atlas, ed 7. Brussels, International Diabetes Federation, 2015.
2.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Peters AL, Tsapas A, Wender R, Matthews DR: Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140–149.
3.
Ferrannini E, Mingrone G: Impact of different bariatric surgical procedures on insulin action and β-cell function in type 2 diabetes. Diabetes Care 2009; 32: 514–520.
4.
Klein S, Fabbrini E, Patterson BW, Polonsky KS, Schiavon CA, Correa JL, Salles JE, Waj­chenberg BL, Cohen R: Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity (Silver Spring) 2012; 20: 1266–1272.
5.
Rubino F, Marescaux J: Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg 2004; 239: 1–11.
6.
Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J: The mechanisms of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 2006; 244: 741–749.
7.
Rajagopalan H, Cherrington AD, Thompson CC, Kaplan LM, Rubino F, Mingrone G, Becerra P, Rodriguez P, Vignolo P, Caplan J, Rodriguez L, Galvao Neto MP: Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study. Diabetes Care 2016; 39: 2254–2261.
8.
van Baar ACG, Devière J, Costamagna G, et al: A single endoscopic duodenal mucosal resurfacing procedure exerts a sustained improvement in hepatic transaminase levels in a cohort of type 2 diabetes patients (abstract LB-35). AASLD 2016. http://www.aasld.org/sites/default/files/LBA%20Full%20Abstracts%20Final%20%28Trimmed%29_1.pdf.

Live case presented during the 35th GEEW 2017, Brussels, Belgium.

© 2018 S. Karger AG, Basel
2018
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