Intestinal Remodeling And Reprogramming of Glucose Metabolism Following Laparoscopic Roux-en-Y Gastric Bypass

The purpose of this study is to investigate small intestinal remodeling and reprogramming of glucose metabolism in patients with Type 2 Diabetes Mellitus (T2DM) who undergo laparoscopic Roux-en-Y Gastric Bypass (RYGB). Our specific goal is to determine if the gene and protein expression levels of GLUT-1 are up regulated in the Roux limb and whether this is a major mechanism for the remission of T2DM following RYGB.

The two aims of the study are: 1) to demonstrate that the basement membrane glucose transporter 1 (GLUT-1) is upregulated in the Roux limb following RYGB, and 2) to demonstrate that the upregulation of GLUT-1 is a major mechanism for the improvement in glycemic control observed in T2DM patients undergoing RYGB.

Study Overview

• Status: Withdrawn
• Conditions: Obesity; Type 2 Diabetes
• Intervention / Treatment: Other: Mix Nutrient Meal; Other: labs; Other: Biopsy; Other: Second Mix Nutrient Meal; Other: Second biopsy; Device: PET/CT

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Type 2 Diabetes Mellitus
2. Age between 18 and 65 years of age
3. BMI > 35kg/m²
4. Diagnosis of gastritis, esophagitis, ulcer, or other mucosal abnormality discovered at routine preoperative upper endoscopy, requiring follow-up endoscopy in the post-operative period.

Exclusion Criteria:

1. Patients undergoing revision from another bariatric procedure to RYGB
2. Presence of a seizure disorder (GLUT-1 deficiency syndrome)
3. Use of Tricyclic antidepressants
4. Use of tobacco products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: RYGB with mucosal abnormality on EGD; Subjects with Type 2 Diabetes undergoing a Roux-en-Y Gastric Bypass with a diagnosis of gastritis, esophagitis, ulcer, or other mucosal abnormality discovered at routine preoperative upper endoscopy, requiring follow-up endoscopy in the post-operative period.

Other: Mix Nutrient Meal; Before Surgery: Subjects will have a visit where they will have a mixed nutrient stimulation test. They will be asked to fast for 12 hours prior to this visit (except water). During the visit they will drink an 8 ounce mixed nutrient liquid meal in 5 minute intervals over 20 minutes. During this visit a catheter will be placed in a vein in their arm for blood sample collections. A total of 50 ml of blood will be collected, (10 ml before drinking the mixed nutrient drink, at 30 minutes, at 60 minutes, at 90 minutes and 120 minutes after the mixed nutrient drink).; Other: labs; Fasting Plasma Glucose (FPG) and insulin will be added to the standard pre-operative labs.; Other: Biopsy; Intra-operatively: Subjects will undergo a standard laparoscopic Roux-en-Y Gastric Bypass (RYGB). During the surgery a 2cm tissue sample of the Roux limb will be taken by the doctor and frozen.; Other: Second Mix Nutrient Meal; 2 months post-operatively a second mixed nutrient stimulation test will be performed following the same process used pre-operatively.; Other: Second biopsy; . Patients will also be scheduled to undergo a second upper endoscopy and a 2cm biopsy of the Roux limb will be taken by the doctor and frozen in liquid nitrogen.; Device: PET/CT; Lastly, subjects will have a positron emission tomography/computed tomography (PET/CT) scan with Fluorodeoxyglucose (FDG) to evaluate the glucose in the Roux limb after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elevated Glut-1 gene and protein expression levels	Gene and protein expression levels of GLUT-1 will be analyzed from the specimens obtained intra-operatively (baseline) and at 2 months post-operatively to determine if levels are significantly elevated above baseline. Quantitative real-time PCR and Western blot techniques will be utilized as described in C below.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glut-1 level change in fasting glucose	Change in GLUT-1 levels will be correlated with changes in fasting glucose, mixed meal stimulation test, and homeostasis model assessment (HOMA). Secondly, at 2 months post-operatively, whole-body positron emission tomography/computed tomography (PET/CT) scanning with Fluorodeoxyglucose (FDG) will be performed to evaluate glucose uptake and utilization in the Roux limb.	2 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Society of American Gastrointestinal and Endoscopic Surgeons
• Investigators: Principal Investigator: Philip Omotosho, MD, Duke University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: November 7, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Estimate): December 26, 2016
• Last Update Submitted That Met QC Criteria: December 23, 2016
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Roux-en-Y gastric bypass
• Other Study ID Numbers: Pro00054934