Type 2 Diabetes Mellitus, Obesity
Conditions
Keywords
Bariatric Surgery, Weight loss
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.
Interventions
PROCEDURERoux-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.
BEHAVIORALCaloric 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.
DRUGExendin-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.
DRUGNormal 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.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Glucose | At baseline and 12 weeks post intervention | Blood sample taken after an overnight fast. |
| Peak Glucose | baseline and 12 weeks post intervention | Blood sample taken after a meal. |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
Subjects that have undergone Roux-en-Y Gastric Bypass (RYGB) and were enrolled in the RYGB arm of trial period 'Study 1-RYGB vs Caloric Restriction', will be enrolled in the second trial period 'Study 2-Exendin (9,39) Amide study' 4 weeks postoperatively.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 3 |
| 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.
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. | 9 |
| 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.
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. | 1 |
| 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.
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. | 0 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Study 1 - RYGB vs Caloric Restriction | Withdrawal by Subject | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Roux-en-Y Gastric Bypass (RYGB) | Caloric Restriction | Total | Exendin-9,39 | Normal Saline |
|---|---|---|---|---|---|
| Age, Categorical Study 1-RYGB vs Caloric Restriction <=18 years | 0 Participants | 0 Participants | 0 Participants | — | — |
| Age, Categorical Study 1-RYGB vs Caloric Restriction >=65 years | 0 Participants | 0 Participants | 0 Participants | — | — |
| Age, Categorical Study 1-RYGB vs Caloric Restriction Between 18 and 65 years | 3 Participants | 9 Participants | 12 Participants | — | — |
| Age, Categorical Study 2-Exendin (9,39) Amide Study <=18 years | — | — | 0 Participants | 0 Participants | — |
| Age, Categorical Study 2-Exendin (9,39) Amide Study >=65 years | — | — | 0 Participants | 0 Participants | — |
| Age, Categorical Study 2-Exendin (9,39) Amide Study Between 18 and 65 years | — | — | 1 Participants | 1 Participants | — |
| Ethnicity (NIH/OMB) Study 1-RYGB vs Caloric Restriction Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Ethnicity (NIH/OMB) Study 1-RYGB vs Caloric Restriction Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | — | 0 Participants |
| Ethnicity (NIH/OMB) Study 1-RYGB vs Caloric Restriction Unknown or Not Reported | 2 Participants | 9 Participants | 11 Participants | — | 0 Participants |
| Ethnicity (NIH/OMB) Study 2-Exendin (9,39) Amide Study Hispanic or Latino | — | — | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) Study 2-Exendin (9,39) Amide Study Not Hispanic or Latino | — | — | 1 Participants | 1 Participants | — |
| Ethnicity (NIH/OMB) Study 2-Exendin (9,39) Amide Study Unknown or Not Reported | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction Asian | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction Black or African American | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction More than one race | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Study 1-RYGB vs Caloric Restriction White | 3 Participants | 9 Participants | 12 Participants | — | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study American Indian or Alaska Native | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study Asian | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study Black or African American | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study More than one race | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study Unknown or Not Reported | — | — | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Study 2-Exendin (9,39) Amide Study White | — | — | 1 Participants | 1 Participants | — |
| Region of Enrollment United States | 3 participants | 9 participants | 12 participants | 1 participants | — |
| Sex: Female, Male Study 1-RYGB vs Caloric Restriction Female | 2 Participants | 6 Participants | 8 Participants | — | 0 Participants |
| Sex: Female, Male Study 1-RYGB vs Caloric Restriction Male | 1 Participants | 3 Participants | 4 Participants | — | 0 Participants |
| Sex: Female, Male Study 2-Exendin (9,39) Amide Study Female | — | — | 1 Participants | 1 Participants | — |
| Sex: Female, Male Study 2-Exendin (9,39) Amide Study Male | — | — | 0 Participants | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 9 | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 3 | 0 / 9 | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 0 / 9 | 0 / 1 | 0 / 0 |
Outcome results
Primary
Changes in the Gut Microbiome Following RYGB or Caloric Restriction
Stool sample collection for gut microbiome analysis
Time frame: baseline and 12 weeks post intervention
Population: No participants samples were analyzed due to inability to obtain funding to proceed with gut microbiome analysis.
Primary
Fasting Glucose
Blood sample taken after an overnight fast.
Time frame: At baseline and 12 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) | Fasting Glucose | Baseline | 6.1 mmol/l | Standard Deviation 0.88 |
| Roux-en-Y Gastric Bypass (RYGB) | Fasting Glucose | 12 weeks post intervention | 6.48 mmol/l | Standard Deviation 1.7 |
| Caloric Restriction | Fasting Glucose | 12 weeks post intervention | 5.89 mmol/l | Standard Deviation 0.4 |
| Caloric Restriction | Fasting Glucose | Baseline | 7.23 mmol/l | Standard Deviation 0.98 |
Primary
Fasting Glucose
Blood sample taken after an overnight fast.
Time frame: 4 weeks post intervention
Population: The number of participants analyzed for the Normal Saline group at 4 weeks post intervention is zero because no subjects were enrolled in this arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) | Fasting Glucose | 4.75 mmol/l |
Primary
Glucose AUC
Area under the curve calculated from Oral Glucose Tolerance Test
Time frame: 0 to 360 minutes post-meal at Baseline and 12 weeks post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) | Glucose AUC | Baseline | 2815 mmol/l.min | Standard Deviation 223 |
| Roux-en-Y Gastric Bypass (RYGB) | Glucose AUC | 12 weeks post intervention | 3146 mmol/l.min | Standard Deviation 1186 |
| Caloric Restriction | Glucose AUC | Baseline | 2715 mmol/l.min | Standard Deviation 375 |
| Caloric Restriction | Glucose AUC | 12 weeks post intervention | 2380 mmol/l.min | Standard Deviation 139 |
Primary
Peak Glucose
Blood sample taken after a meal.
Time frame: baseline and 12 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) | Peak Glucose | Baseline | 11.35 mmol/l | Standard Deviation 1.5 |
| Roux-en-Y Gastric Bypass (RYGB) | Peak Glucose | 12 weeks post intervention | 11.8 mmol/l | Standard Deviation 3.25 |
| Caloric Restriction | Peak Glucose | Baseline | 10.84 mmol/l | Standard Deviation 1.39 |
| Caloric Restriction | Peak Glucose | 12 weeks post intervention | 10.04 mmol/l | Standard Deviation 0.54 |
Primary
Peak Glucose
Blood sample taken after a meal.
Time frame: 4 weeks post intervention
Population: The number of participants analyzed for the Normal Saline group at 4 weeks post intervention is zero because no subjects were enrolled in this arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roux-en-Y Gastric Bypass (RYGB) | Peak Glucose | 8.15 mmol/l |