1. Insulin sensitivity and beta cell function after duodenal mucosal resurfacing: an open-label, mechanistic, pilot study.
- Author
-
Busch CBE, Meiring S, van Baar ACG, Gastaldelli A, DeFronzo R, Mingrone G, Hagen M, White K, Rajagopalan H, Nieuwdorp M, and Bergman JJGHM
- Subjects
- Female, Humans, Male, Middle Aged, C-Peptide blood, C-Peptide metabolism, Endoscopic Mucosal Resection methods, Glucagon metabolism, Glycated Hemoglobin metabolism, Pilot Projects, Blood Glucose metabolism, Diabetes Mellitus, Type 2 metabolism, Duodenum surgery, Duodenum metabolism, Gastric Inhibitory Polypeptide metabolism, Glucagon-Like Peptide 1 metabolism, Insulin metabolism, Insulin Resistance, Insulin-Secreting Cells metabolism, Intestinal Mucosa metabolism, Intestinal Mucosa surgery
- 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 noninsulin glucose-lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2 studies. Inclusion criteria were a hemoglobin A1c from 7.6% to 10.4% and a body mass index of 24 to 40 kg/m
2 . Baseline and 3-month 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) and beta cell function (insulinogenic index, 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 hepatic insulin resistance) and beta cell function (DI and ISR) all improved significantly. Declines in postprandial glucose, mainly driven by a decrease in fasting levels, and in postprandial glucagon were observed, 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. (Clinical trial registration numbers: NCT02413567 and NCT03653091.)., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Gastaldelli: Consultant for Eli Lilly and Fractyl Health Inc.; speaker for Eli Lilly and Novo Nordisk; advisory boards for Boehringer-Ingelheim, Novo Nordisk, Metadeq, and Pfizer; research support from Eli Lilly; advisory board and paid chair in symposia at MSD-Merck; grant review panel for Pfizer. R. DeFronzo: Advisory board for AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia, Renalytix, and Corcept Therapeutics; research support from Boehringer-Ingelheim, AstraZeneca, and Merck; speaker for AstraZeneca. G. Mingrone: Consultant for Novo Nordisk, Fractyl, and Recor; scientific advisor for Metadeq, Keyron, GHP Scientific, and Jemyll. M. Hagen, K. White, H. Rajagopalan: Employees and shareholders of Fractyl Health Inc. M. Nieuwdorp: Research support from ZONMW-VICI; J. J. G. H. M. Bergman: Research support from Fractyl Health Inc., Endogenex, and Digma Medical; consultant for Fractyl Health Inc., and Endogenex. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF