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 Microbiome in Patients With Type 2 Diabetes

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?

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.