The Effect of Bariatric Surgery on Metabolism, the Metabolome and Microbiome in Patients With Type 2 Diabetes (Microbiome)

The Effect of Bariatric Surgery on Metabolism, the Metabolome and the Microbiome in Patients With Type 2 Diabetes

What are the benefits of undergoing Roux-en-Y gastric bypass surgery in improving type 2 diabetes outside of weight loss alone?

Study Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes Mellitus
• Intervention / Treatment: Procedure: Roux-en-Y Gastric Bypass (RYGB); Behavioral: Caloric Restriction; Drug: Exendin-9,39; Drug: Normal Saline

Detailed Description

Roux-en-y gastric bypass (RYGB) surgery leads to improvements in diabetes that occurs even before any significant weight loss is seen. What are the reasons for this? There is evidence in animals that changes in the composition of gut bacteria after RYGB may be responsible for improvements in how glucose is metabolized in the body. The study aims to correlate changes in the bacterial composition of the gut that occurs after surgery with improvements in glucose metabolism in people with type 2 diabetes. The investigators will do this by using validated methods to measure glucose metabolism and cutting edge technology to analyze the gut microbiome. A parallel group of patients with similar weight, height and age will undergo caloric restriction alone to mimic weight loss seen after RYGB. Participants will also undergo similar glucose metabolism studies and analysis of their gut bacterial composition. Thus, any difference seen between groups can be attributed to the surgery itself and may lead to identification of novel therapeutic options for diabetes.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 20-65 years of age.
• Seen at Mayo Clinic Nutrition Clinic and have received authorization for RYGB surgery.
• Type 2 Diabetes Mellitus or impaired fasting glucose with BMI >35 AND not interested in surgery but are interested in supervised caloric restriction.

Exclusion Criteria:

• Previous treatment with thiazolidinediones.
• Chronic antibiotic therapy.
• Active microvascular or macrovascular complications of diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Roux-en-Y Gastric Bypass (RYGB); Subjects between the ages of 20-65 years of age seen for weight management in the Nutrition Clinic at Mayo Clinic, who have been approved for RYGB.	Procedure: Roux-en-Y Gastric Bypass (RYGB); Subjects will be studied prior to surgical intervention and 12 weeks post surgery. Subjects in surgical arm will start diet intervention after surgery. Follow up with dietary will be per standard of care following RYGB surgery.; Other Names: Bariatric Surgery
Sham Comparator: Caloric restriction; Subjects between the ages of 20-65 years of age, with diagnosis of Type 2 diabetes mellitus or impaired fasting glucose. Subjects will undergo caloric restriction alone to mimic weight loss seen after gastric bypass surgery.	Behavioral: Caloric Restriction; Subjects participating in caloric arm of this study will be asked to consume an identical diet that is controlled for caloric content and macronutrient composition. This is identical to that consumed by patient undergoing RYGB. Subjects in the caloric restriction arm will start the diet after the screening visit. Compliance will be monitored by alternating weekly meetings with a clinical psychologist and dietician.
Active Comparator: Exendin-9,39; Four subjects who have undergone RYGB surgery will be studied 4 weeks after surgery. Subjects will be randomized to receive an infusion of Exendin-9,39 or normal saline.	Drug: Exendin-9,39; A subset of 4 subjects who have undergone RYGB surgery will be studied 4 weeks after surgery. Subjects will be randomized to receive an infusion of either Exendin-9,39 or normal saline. Exendin-9,39 blocks the action of specific hormones called "incretins" that are produced by the gut in health and in larger quantities after gastric bypass surgery.
Placebo Comparator: Normal Saline; Four subjects who have undergone RYGB surgery will be studied 4 weeks after surgery. Subjects will be randomized to receive an infusion of Exendin-9,39 or normal saline.	Drug: Normal Saline; subset of 4 subjects who have undergone RYGB surgery will be studied 4 weeks after surgery. Subjects will be randomized to receive an infusion of either Exendin-9,39 or normal saline. Exendin-9,39 blocks the action of specific hormones called "incretins" that are produced by the gut in health and in larger quantities after gastric bypass surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Glucose	Blood sample taken after an overnight fast.	At baseline and 12 weeks post intervention
Fasting Glucose	Blood sample taken after an overnight fast.	4 weeks post intervention
Peak Glucose	Blood sample taken after a meal.	baseline and 12 weeks post intervention
Peak Glucose	Blood sample taken after a meal.	4 weeks post intervention
Glucose AUC	Area under the curve calculated from Oral Glucose Tolerance Test	0 to 360 minutes post-meal at Baseline and 12 weeks post-intervention
Changes in the Gut Microbiome Following RYGB or Caloric Restriction	Stool sample collection for gut microbiome analysis	baseline and 12 weeks post intervention

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Meera Shah, MBChB, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): January 6, 2018
• Study Completion (Actual): January 6, 2018

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Weight loss; Bariatric Surgery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 15-000179

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No