Insulin sensitivity and beta cell function after Duodenal Mucosal Resurfacing (DMR): An Open-Label, Mechanistic, Pilot Study

Celine B E Busch; Suzanne Meiring; Annieke C G van Baar; Amalia Gastaldelli; Ralph DeFronzo; Geltrude Mingrone; Moira Hagen; Kelly White; Harith Rajagopalan; Max Nieuwdorp; Jacques J G H M Bergman

doi:10.1016/j.gie.2024.01.031

Insulin sensitivity and beta cell function after Duodenal Mucosal Resurfacing (DMR): An Open-Label, Mechanistic, Pilot Study

Gastrointest Endosc. 2024 Jan 25:S0016-5107(24)00049-X. doi: 10.1016/j.gie.2024.01.031. Online ahead of print.

Authors

Affiliations

¹ PhD candidate, Gastroenterology and Hepatology, Amsterdam University Medical Centres, location AMC, Amsterdam, the Netherlands.
² Postdoctoral researcher, Gastroenterology and Hepatology, Amsterdam University Medical Centres, location AMC, Amsterdam, the Netherlands;. Electronic address: a.c.vanbaar@amsterdamumc.nl.
³ Cardiometabolic Risk Laboratory, CNR Institute of Clinical Physiology, Pisa, Italy.
⁴ Diabetes Division, University of Texas Health Science Center; Texas Diabetes Institute, San Antonio, TX.
⁵ Fondazione Policlinico Universitario A. Gemelli IRCCS Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom.
⁶ Fractyl Health.
⁷ Internal and Vascular Medicine, Amsterdam University Medical Centres, location AMC, Amsterdam, the Netherlands.
⁸ Gastroenterologist, Gastroenterology and Hepatology, Amsterdam University Medical Centres, location AMC, Amsterdam, the Netherlands.

PMID: 38280531
DOI: 10.1016/j.gie.2024.01.031

Abstract

Background and aims: The duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR.

Methods: We included 28 patients on non-insulin glucose lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2. Inclusion criteria were hemoglobin A1c (HbA1c) 7.6-10.4% and BMI 24-40kg/m². Baseline and 3-months MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (homeostatic model assessment for insulin resistance [HOMA-IR], Matsuda index [MI] and hepatic insulin resistance [HIR]), and beta cell function (insulinogenic index [IGI], disposition index [DI] and insulin secretion rate [ISR]) were assessed.

Results: Fasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and HIR) and beta cell function (DI and ISR) all improved significantly. Decline in postprandial glucose, mainly driven by a decrease in fasting levels, was observed, as well as a decline in postprandial glucagon whereas GLP-1 and GIP did not change.

Conclusions: Insulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D.

Keywords: Duodenal mucosal resurfacing (DMR); glucoregulatory hormones; incretins; metabolic endoscopy; mixed meal test (MMT); therapeutic endoscopy; type 2 diabetes (T2D).