From Endoscopic Inspection to Gene-Expression: A Thorough Assessment of the Duodenal Mucosa After Resurfacing—A Prospective Study

Aims: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycemia in patients with type 2 diabetes mellitus (T2DM). Although the exact underlying mechanism is still unclear, it is postulated that the DMR-induced improvements are the result of changes in the duodenal mucosa. For this reason, we assessed macroscopic and microscopic changes in the duodenal mucosa induced by DMR + GLP-1RA. Methods: We included 16 patients with T2DM using basal insulin that received a combination treatment of a single DMR and GLP-1RA. Endoscopic evaluation was performed before the DMR procedure and 3 month after, and duodenal biopsies were obtained. Histological evaluation was performed and L and K cell density was calculated. In addition, gene-expression analysis and Western blotting was performed. Results: Endoscopic evaluation at 3 month showed duodenal mucosa with a normal appearance. In line, microscopic histological evaluation showed no signs of villous atrophy or inflammation and unchanged L and K cell density. Unbiased transcriptome profiling and western blotting revealed that PDZK1 expression was higher in responders at baseline and after DMR. GATA6 expression was significantly increased in responders after DMR compared to non-responders. Conclusion: The absence of macroscopic and microscopic changes after 3 month suggest that improvements in glycemic parameters after DMR do not result from significant histological changes in duodenal mucosa. It is more likely that these improvements result from more subtle changes in enteroendocrine signaling. PDZK1 and GATA6 expression might play a role in DMR; this needs to be confirmed in pre-clinical studies.