Alternative treatments for type 2 diabetes and associated metabolic diseases: medical therapy or endoscopic duodenal mucosal remodelling?

Baar, Annieke C.G. van; Meiring, Suzanne; Holleman, F.; Hopkins, David; Mingrone, Geltrude; Devière, Jacques; Nieuwdorp, Max; Bergman, Jacques

doi:10.1136/gutjnl-2020-323931

Cited by 9 publications

(5 citation statements)

References 39 publications

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“… 36,37 Several studies have confirmed GIP suppression following endoscopic DMR for MS treatment; however, adverse events are inevitable because of thermal energy. 17,38,39 Therefore, we focused on PDT-DMR to avoid affecting the deep mucosal layers. Na et al have confirmed the potential for treating obesity with T2DM by inhibiting GIP release from the K-cells using endoscopic PDT in an in vivo model.…”

Section: Discussionmentioning

confidence: 99%

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Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model

Park,

Park

et al. 2024

APL Bioengineering

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Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, DMR methods using lasers, pulsed electric fields, radio frequency, steam, and cryoablation have been developed for other sites, such as the Barrett's esophagus; however, they are in pre-clinical trial stages and require procedural development for clinical application to humans. 17 …”

Section: Introductionmentioning

confidence: 99%

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model

Park,

Park

et al. 2024

APL Bioengineering

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“…However, because of safety concerns, the DJBL does not seem to be an ideal treatment option for improving insulin resistance and other MetSyn parameters (71). Last, the DMR procedure ablates approximately 10-15 cm of the duodenal mucosa, to induce healthy regeneration thereof (72). It has been shown to significantly improve glycemic control, insulin resistance, and liver fat percentage in patients with T2D even in a controlled setting (73,74).…”

Section: Surgical and Endoscopic Interventionsmentioning

confidence: 99%

Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity

Busch,

Bergman,

Nieuwdorp

et al. 2024

Am J Gastroenterol

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The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges, due to its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together these abnormalities increase the cardiovascular risk for individuals and pose a threat for healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines, and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial as they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.

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“…53 While the mechanisms may be multifactorial, an increase in GLP-1 levels and bile acids (at least in rodents) may be involved. Experimental, non-surgical procedures collectively called 'duodenal exclusion therapies'-which include the duodenal-jejunal bypass sleeve 54 and duodenal mucosal resurfacing 55 -have given related results regarding incretin secretion.…”

Section: Gastrointestinal Bypass Proceduresmentioning

confidence: 99%

Endogenous glucagon‐like peptide (GLP)‐1 as alternative for GLP‐1 receptor agonists: Could this work and how?

Smits

Holst

2023

Diabetes Metabolism Res

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In recent years, we have witnessed the many beneficial effects of glucagon‐like peptide (GLP)‐1 receptor agonists, including the reduction in cardiovascular risk in patients with type 2 diabetes, and the reduction of body weight in those with obesity. Increasing evidence suggests that these agents differ considerably from endogenous GLP‐1 when it comes to their routes of action, although their clinical effects appear to be the same. Given the limitations of the GLP‐1 receptor agonists, could it be useful to develop agents which stimulate GLP‐1 release? Here we will discuss the differences and similarities between GLP‐1 receptor agonists and endogenous GLP‐1, and will detail how endogenous GLP‐1—when stimulated appropriately—could have clinically relevant effects.

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Alternative treatments for type 2 diabetes and associated metabolic diseases: medical therapy or endoscopic duodenal mucosal remodelling?

Abstract: Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Cited by 9 publications

References 39 publications

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model

Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity

Endogenous glucagon‐like peptide (GLP)‐1 as alternative for GLP‐1 receptor agonists: Could this work and how?

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