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Jonah Hoyt, BS

Job Title

Clinical Research Coordinator

Academic Rank

Staff/Research Assistant

Department

Endocrinology

Authors

Jonah Hoyt

Principal Investigator

Vanita Aroda, M.D.

Categories

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A Look at Duodenal Mucosal Resurfacing: Rationale for Targeting the Duodenum in Type 2 Diabetes

Scientific Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is progressive and chronic disease leading to a variety of complications and is a major health burden of modern society. Despite the availability of multiple medications, less than half of all people living with T2DM reach their glycemic target. Recently, the gastrointestinal tract has emerged as a target for treating T2DM.

Objective: We examine the underlying physiology of the duodenum, its role in T2DM pathogenesis, the rationale for targeting the duodenum via DMR as a treatment of T2DM, and clinical data on the safety and efficacy of DMR for the treatment of T2DM.

Methods: We searched the literature to synthesize the scientific rationale behind targeting the duodenum with DMR.

Results: Preclinical studies have elucidated changes in the duodenal mucosa potentially caused by dietary excess and obesity which is also seen in individuals with metabolic disease. Early clinical trial data indicate improvements in glycemic control with overall safety. DMR has been demonstrated to change some of the mucosal abnormalities common to T2DM.

Conclusions: The duodenum is a viable target to address metabolic abnormalities in T2DM. Ongoing studies will characterize the full metabolic effect of DMR as a potential treatment of T2DM.

Lay Abstract

Type 2 Diabetes (T2DM) is a disease that can lead to a wide variety of complications and is one of the major health burdens of society. Those with T2DM require long-term therapies to reduce blood glucose. However, less than half of all people living with T2DM reach their sugar targets despite the availability of oral and injectable medications. To date no disease altering approaches have been developed. The gastrointestinal tract has emerged as a direct target for treating T2DM. Studies have elucidated changes in the mucosal layer of the duodenum caused by dietary excess and obesity, which is prevalent among individuals with metabolic disease. From this perspective, we explore the rationale behind targeting the duodenum with Duodenal Mucosal Resurfacing (DMR). We examine the underlying physiology of the duodenum and its role in the development of T2DM, the rationale for targeting the duodenum via DMR as a potential treatment of type 2 diabetes, and current data surrounding DMR. Importantly, DMR has been demonstrated to change some of the mucosal abnormalities common to obesity and diabetes and ongoing trials will assess its potential for long-lasting metabolic benefit.

Clinical Implications

Given the complex multifactorial etiology of T2DM, understanding proximate contributors to disease pathogenesis opens the door to rethinking our therapeutic approach to T2DM from symptom management towards disease modification.