Exploring How Duodenal Mucosal Resurfacing Impacts Diabetes Control Using UHPLC-MS/MS

A joint study between the Nanjing University of Chinese Medicine (Jiangsu Province, China) and Virginia Commonwealth University (Richmond, Virginia) set out to investigate the mechanisms by which duodenal mucosal resurfacing (DMR) improves metabolic disorders using a rat model. Serum assays measured glucose, lipid profiles, lipopolysaccharide, and intestinal hormones, while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A paper based on this work was published in World Journal of Diabetes (1).

Influenced by genetics, environmental factors, stress, diet, lifestyle, and various other elements, incidents of type 2 diabetes (T2D) are on the rise, with a projected global prevalence expected to reach 12.2% by 2045 (2,3). For patients with T2D, the damage to tissues and organs that the disease causes an increase in the incidences of complications, which in turn leads to increased morbidity and mortality, affecting both longevity and quality of life. Despite the availability of advanced lifestyle interventions and medical treatment for T2D, over half of affected individuals do not attain the treatment goal of achieving a glycemic hemoglobin level ≤ 53 mmol/mol (4).

The pathogenesis of T2D has an intricate and multifaceted pathogenesis, with insulin resistance serving as the central mechanism (5). The contribution of the stomach and small intestine to T2D pathogenesis is being increasingly recognized, and data collected contributies to the emergence of metabolic surgery as a viable option (6,7). Recent research underscoring the duodenum as an important metabolic signaling center, where duodenal dysfunction emerges as a driving factor for insulin resistance in T2D patients (particularly linked to abnormal hyperplasia of the duodenal mucosa), has emerged (8-10).

To address this mucosal abnormality, researchers have developed a DMR procedure, a minimally invasive endoscopic hydrothermal ablation technique that can be performed in an outpatient setting (11,12). Considering the complexity of T2D pathogenesis, the analysts conducting the study hypothesized that DMR may exert a regulatory effect on metabolic processes via multiple pathways (1).

Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa, which was then evaluated through the use ofhistology, immunofluorescence, and western blotting. Serum assays measuring glucose, lipid profiles, lipopolysaccharide, and intestinal hormones were performed, while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and UHPLC-MS, severally. Analysis determined that DMR significantly improves the glucose and lipid metabolic disorders in the sample population of rats researched, increases serum levels of cholecystokinin, gastric inhibitory peptide, and glucagon-like peptide 1, and reduces the length and depth of duodenal villi and crypts. DMR also enhanced the intestinal barrier integrity, and reduced lipopolysaccharide translocation. Furthermore, DMR modified the gut microbiome and metabolome, particularly affecting the Blautia genus. In addition, correlation scrutiny exposed noteworthy between the gut microbiota, metabolites, and T2D phenotypes (1).

The researchers wrote that their findings strongly indicate the importance of the duodenal mucosa in the pathogenesis and treatment of T2D, and that DMR may effectively alleviate insulin resistance and metabolic disorders in T2D rats through a multitude of pathways, including a reduction of villus length and crypt depth, augmentation of intestinal hormone secretion, reinforcement of intestinal barrier function, reduction in LPS leakage, and modulation of gut microbiota and metabolites. They state that their study serves as a preliminary investigation, and while they believe that further animal experiments are required to corroborate their findings, their findings nevertheless provide the theoretical groundwork for potential clinical application of the DMR procedure in humans with T2D (1).

Laboratory rat in plastic box on table, scientist mixing chemical in tube. © motortion - stock.adobe.com

References

1. Nie, L. J.; Cheng, Z.; He, Y. X. et al. Role of Duodenal Mucosal Resurfacing in Controlling Diabetes in Rats. World J. Diabetes 2025, 16 (3), 102277 DOI: 10.4239/wjd.v16.i3.102277]

2. Cho, N. H.; Shaw, J. E.; Karuranga, S. et al. IDF Diabetes Atlas: Global Estimates of Diabetes Prevalence for 2017 and Projections for 2045. Diabetes Res. Clin. Pract. 2018,138, 271-281. DOI: 10.1016/j.diabres.2018.02.023

3. Sun, H.; Saeedi, P.; Karuranga, S. et al. IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045. Diabetes Res. Clin. Pract. 2022, 183, 109119. DOI: 10.1016/j.diabres.2021.109119

4. Resnick, H. E.; Foster, G. L.; Bardsley, J. et al. Achievement of American Diabetes Association Clinical Practice Recommendations Among U.S. Adults with Diabetes, 1999-2002: The National Health and Nutrition Examination Survey. Diabetes Care 2006, 29(3), 531-537. DOI: 10.2337/diacare.29.03.06.dc05-1254

5. Ahmad, E.; Lim, S.; Lamptey, R. et al. Type 2 Diabetes. Lancet 2022, 400(10365), 1803-1820. DOI: 10.1016/S0140-6736(22)01655-5

6. Caiazzo, R.; Lassailly, G.; Leteurtre, E. et al. Roux-en-Y Gastric Bypass Versus Adjustable Gastric Banding to Reduce Nonalcoholic Fatty Liver Disease: A 5-year Controlled Longitudinal Study. Ann. Surg. 2014, 260(5), 893-899. DOI: 10.1097/SLA.0000000000000945

7. Wu, W.; Lin, L.; Lin, Z. et al. Duodenum Exclusion Alone Is Sufficient to Improve Glucose Metabolism in STZ-Induced Diabetes Rats. Obes. Surg. 2018, 28(10), 3087-3094. DOI: 10.1007/s11695-018-3291-z

8. Cherrington, A. D.; Rajagopalan, H.; Maggs, D. et al. Hydrothermal Duodenal Mucosal Resurfacing: Role in the Treatment of Metabolic Disease. Gastrointest. Endosc. Clin. N. Am. 2017, 27(2), 299-311. DOI: 10.1016/j.giec.2016.12.002

9. Pereira, J. N. B.; Murata, G. M.; Sato, F. T. et al. Small Intestine Remodeling in Male Goto-Kakizaki Rats. Physiol. Rep. 2021, 9(3), e14755. DOI: 10.14814/phy2.14755

10. Nie, L.; Yan, Q.; Zhang, S. et al. Duodenal Mucosa: A New Target for the Treatment of Type 2 Diabetes. Endocr. Pract. 2023, 29(1), 53-59. DOI: 10.1016/j.eprac.2022.10.177

11. Haidry, R. J.; van Baar, A. C.; Galvao Neto, M. P. et al. Duodenal Mucosal Resurfacing: Proof-of-Concept, Procedural Development, and Initial Implementation in the Clinical Setting. Gastrointest. Endosc. 2019, 90(4), 673-681.e2. DOI: 10.1016/j.gie.2019.03.024

12. Mingrone, G.; van Baar, A. C.; Devière, J. et al. Safety and Efficacy of Hydrothermal Duodenal Mucosal Resurfacing in Patients with Type 2 Diabetes: The Randomised, Double-Blind, Sham-Controlled, Multicentre REVITA-2 Feasibility trial. Gut 2022, 71(2), 254-264. DOI: 10.1136/gutjnl-2020-323608