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Improving Glycemic Control Through Resurfacing of the Duodenum

What benefits can be obtained from duodenal mucosal resurfacing?

Glucose metabolism in the human body is quite complex and imbalances in such processes can be observed in our diabetes patients. Current treatment efforts focus on correcting, or at least normalizing, these metabolic imbalances through dietary approaches in conjunction with novel oral and injectable drugs. However, metabolic factors and medication adherence hinder the possibility of obtaining adequate glycemic control. Bariatric surgery has been shown to provide protective effects on glucose metabolism in diabetes patients. There is growing evidence supporting such surgeries. In experimental studies, surgeries that focus on intestinal bypass, specifically the duodenum, provides positive direct effects on glucose metabolism. In the presence of metabolic disorders, such as diabetes, the duodenal mucosa experiences hypertrophy and endocrine hyperplasia. These effects lead to improper glucose uptake and absorption in the duodenal mucosa leading to dysregulation in glucose homeostasis and insulin sensitivity. Based on these findings, a novel technique has been devised in the efforts of improving health outcomes in diabetes patients. Duodenal mucosal resurfacing (DMR) is a novel, minimally invasive, catheter-based upper endoscopic procedure consisting of hydrothermal ablation of the duodenal mucosa leading, thus providing mucosal healing.

Recently, Harith Rajagopalan and colleagues conducted the first phase I, nonrandomized, open-label trial in humans, which explores the use in duodenal mucosal resurfacing in patients with type 2 diabetes. Patients were eligible to participate in the study if they were ages 28-75 years, with a BMI between 20 and 40 kg/m2, A1c levels between 7.5 and 12%, and at least taking one oral diabetic agent. The aim of the study was to understand the safety and efficacy of this duodenal musical resurfacing technique in diabetes patients. Patients were separated based on the segment of the duodenum where resurfacing was performed. 28 patients underwent surgery for resurfacing of the long segment of the duodenum and 11 patients underwent surgery for resurfacing of the short segment of the duodenum. After the surgery, all 39 patients were given a diet to follow for 2 weeks consisting of liquids, pureed foods, and soft foods; then they were followed for a 6-month period. Minimal to no change was made in the use of diabetic medications. In order to understand the efficacy of this procedure, a mixed-meal tolerance test was performed, followed by measurements of fasting plasma glucose, fasting insulin levels and A1c.

Results from the study demonstrated no gastrointestinal complications from the surgery. There was no evidence of bleeding, severe hypoglycemia, malabsorption, or perforation. A total of 3 patients experienced duodenal stenosis 2-6 weeks after the surgery. These presented with epigastric pain and vomiting. Researchers performed endoscopic balloon dilation of the duodenum until these symptoms resolved. Mucosal healing was observed during the first and third month. There were significant improvements in glucose control. During the first week of follow up, reductions were observed in fasting blood glucose. Subsequently, reductions in A1c were observed at the one-month mark. These improvements were maintained for the duration of the study. There was a 1.2% + reduction in A1c for the full cohort at the end of the study (P<0.001). This effect was more notable in those patients where resurfacing of the long segment of duodenum was done (mean A1c: 2.5 + 0.5%), whereas those patients who underwent resurfacing of the short segment of the duodenum obtained a mean A1c reduction of 1.2 + 0.5% at the 3-month analysis (p<0.05). Finally, greater glycemic improvement was seen in those patients remaining stable on their antidiabetic medication dosages (p=0.11 at 6 months). Significant weight reduction was also observed, independent from A1c improvements.

In conclusion, the use of this novel technique provides a means for better management of type 2 diabetes mellitus. Healing of the duodenal mucosa can be observed in as little as 1 month and was observed throughout the duration of the study period. Significant improvements in fasting blood glucose, A1c, and weight can be obtained from duodenal mucosal resurfacing. These findings highlight the metabolic benefits that can be obtained in type 2 diabetes mellitus. Thus, with adequate pharmacological treatment and in conjunction with this form of bariatric surgery. The role in therapy of this resurfacing technique is yet to be established through more research efforts.  Nonetheless, it shows the potential to be used as an alternative to therapy or in conjunction to current standards of therapy.

Practice Pearls:

  • Duodenal mucosal resurfacing show clinically significant improvements in glucose levels and A1c.
  • Resurfacing the mucosal epithelium decreases the risk of hypertrophy and imbalances in glucose and insulin homeostasis.
  • DMR is well-tolerated and there are minimal incidences of severe adverse events.

Reference:

Rajagopalan, Harith, Alan D. Cherrington, Christopher C. Thompson, Lee M. Kaplan, Francesco Rubino, Geltrude Mingrone, Pablo Becerra, Patricia Rodriguez, Paulina Vignolo, Jay Caplan, Leonardo Rodriguez, and Manoel P. Galvao Neto. “Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6-Month Interim Analysis From the First-in-Human Proof-of-Concept Study.” Diabetes Care Dia Care (2016): Dc160383. Web.

 

Pablo A. Marrero-Núñez – USF College of Pharmacy Student Delegate –  Doctor of Pharmacy Candidate 2017 – University of South Florida – College of Pharmacy