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

Phase 2

Completed

Interventions: Drug: Exendin-9,39
Drug: Normal Saline
Behavioral: Caloric Restriction
Procedure: Roux-en-Y Gastric Bypass (RYGB)

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

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Exendin-9,39	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.
Normal Saline	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.
Caloric restriction	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.
Roux-en-Y Gastric Bypass (RYGB)	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.

Primary Outcome Measures

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