Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results

• Published in: JHEP reports Vol. 1; no. 6; pp. 429 - 437
• Main Authors: van Baar, Annieke C.G., Beuers, Ulrich, Wong, Kari, Haidry, Rehan, Costamagna, Guido, Hafedi, Alia, Deviere, Jacques, Ghosh, Soumitra S., Lopez-Talavera, Juan Carlos, Rodriguez, Leonardo, Galvao Neto, Manoel P., Sanyal, Arun, Bergman, Jacques J.G.H.M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2019; Elsevier
• Subjects: Aminotransferase levels; Blood Glucose; Duodenal Mucosal Resurfacing; Glycated Haemoglobin A1c; Insulin Resistance; Metabolic Syndrome; Metabolomics; NAFLD; Non-Alcoholic Fatty Liver Disease; T2DM; therapeutic endoscopy; Type 2 Diabetes Mellitus; therapeutic endoscopy; T2DM; Metabolomics; NAFLD; Glycated Haemoglobin A1c; Aminotransferase levels; Type 2 Diabetes Mellitus; Metabolic Syndrome; Insulin Resistance; Blood Glucose; Non-Alcoholic Fatty Liver Disease; Duodenal Mucosal Resurfacing
• ISSN: 2589-5559; 2589-5559
• DOI: 10.1016/j.jhepr.2019.10.006

Insulin resistance is a core pathophysiological defect underscoring type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Both conditions improve with duodenal exclusion surgery. Duodenal mucosal resurfacing (DMR) is an endoscopic intervention developed to treat metabolic disease which has been shown to improve glycaemia in patients with poorly controlled T2DM. Herein, we aimed to further analyse the effects of DMR on hepatic and metabolic parameters in this patient cohort.
Eighty-five patients with T2DM who received endoscopic DMR treatment were enrolled from 5 centres and followed up for 6 months. We assessed safety in all patients. Efficacy was evaluated in patients who received at least 9 cm of duodenal ablation (n = 67). Endpoints included HbA1c, fasting plasma glucose, weight and aminotransferase levels. Metabolomic analysis was conducted in a subgroup (n = 14). Data were analysed using paired t test or ANOVA for repeated measures with Bonferroni correction and correction for initial weight loss if applicable.
The DMR procedure was completed with no intraprocedural complications in the entire cohort. HbA1c was lower 6 months after DMR than at baseline (7.9 ± 0.2% vs. 9.0 ± 0.2% [mean ± SE], p ≪0.001). Fasting plasma glucose was also significantly lower 6 months after DMR compared to baseline (161 ± 7 mg/dl vs. 189 ± 6 mg/dl, p = 0.005). Body weight decreased slightly. At 6 months, alanine aminotransferase had decreased from 41 ± 3 IU/L to 29 ± 2 IU/L (p ≪0.001) and aspartate aminotransferase had decreased from 30 ± 2 IU/L to 23 ± 1 IU/L (p ≪0.001). Metabolomic analysis demonstrated that DMR had key lipid-lowering, insulin-sensitizing and anti-inflammatory effects, as well as increasing antioxidant capacity. Mean FIB-4 was also markedly decreased.
Hydrothermal ablation of the duodenum by DMR elicits a beneficial metabolic response in patients with T2DM. DMR also improves hepatic indices, potentially through an insulin-sensitizing mechanism. These encouraging data deserve further evaluation in randomized controlled trials.
Hydrothermal duodenal mucosal resurfacing (DMR) is an endoscopic technique designed to treat metabolic disease through ablation of the duodenal mucosa. DMR is a safe procedure which improves glycaemia and hepatic indices in patients with type 2 diabetes mellitus. DMR is an insulin-sensitizing intervention which can be complementary to lifestyle intervention approaches and pharmacological treatments aimed at preserving the pancreas and liver from failure. DMR is a potential therapeutic solution for patients with type 2 diabetes and fatty liver disease.
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•Duodenal mucosal resurfacing elicits a metabolic benefit in patients with T2DM.•At 6 months post-duodenal mucosal resurfacing, HbA1c decreases by 1.0-1.5%.•In patients with high ALT baseline levels, duodenal mucosal resurfacing elicits an ALT reduction of ~40–50%.•FIB-4 scores decrease significantly after duodenal mucosal resurfacing.•Duodenal mucosal resurfacing elicits insulin-sensitizing, lipid-lowering, anti-inflammatory, and antioxidant effects