Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes

Study Overview
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Brief Summary
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For this purpose, we will compare the effects of targeted 16-18% (with a range of 16-25%) weight loss induced by Roux-en-Y Gastric bypass (RYGB) surgery with the same weight loss induced by a low-calorie diet (LCD) on liver and skeletal muscle insulin sensitivity, beta-cell function, and 24-hour metabolic homeostasis in obese subjects with or without T2D.

Official Title
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Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes

Conditions
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Obesity, Type 2 Diabetes

Intervention / Treatment
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* Procedure: Roux-en-Y gastric bypass surgery
* Behavioral: Low-calorie diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For RYGB group: Scheduled for this bariatric surgery Body Mass Index (BMI) 34-55 kg/m² Type 2 Diabetes Signed informed consent For Low-Calorie Diet group: BMI 34-55 kg/m² Type 2 Diabetes and Non-Diabetics Signed informed consent Exclusion Criteria: For both RYGB & Low-Calorie Diet groups Regular use of tobacco products Previous intestinal resection Pregnant or breastfeeding Evidence of significant organ system dysfunction or disease other than T2D Use of any medication that might, in the opinion of the investigator, affect metabolic function Exercise ≥90 minutes per week

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roux-en-Y gastric bypass (RYGB)<br>Subjects in this group are scheduled to undergo roux-en-Y gastric bypass surgery to obtain approximately 16-18% (with a range of 16-25%) weight loss. | Procedure: Roux-en-Y gastric bypass surgery<br>* A surgical procedure to help subjects lose approximately 16-18% (with a range of 16-25%) of their body weight.<br>|
| Active Comparator: Low-calorie diet<br>Subjects in this group will participate in a low-calorie diet intervention to obtain approximately 16-18% (with a range of 16-25%) weight loss. | Behavioral: Low-calorie diet<br>* Subjects will meet with a dietitian and/or behaviorist over approximately 6 months to lose approximately 16-18% (with a range of 16-25%) of their body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hepatic insulin sensitivity | The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss. | 6 months (before and after targeted weight loss) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in skeletal muscle and adipose tissue insulin sensitivity | The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss. | 6 months (before and after targeted weight loss) | 
| Changes in Beta-cell function | The outcome will be assessed as the product of beta-cell glucose sensitivity (ratio of post-meal insulin secretion rate to post-meal plasma glucose) during mixed-meal test and whole-body insulin sensitivity before and after weight loss. | 6 months (before and after targeted weight loss) | 
| Changes in glucose kinetics (glucose concentration and rate of appearance into the systemic circulation) in response to mixed-meal ingestion | The outcome will be measured by using dual glucose tracer mixed meal metabolic test and serial blood sampling for 4 hours before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in 24-hour plasma glucose profile | The outcome will be determined by obtaining serial plasma glucose concentration measurements for 24 hours before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in 24-hour plasma insulin profile | The outcome will determined by obtaining serial plasma insulin concentration measurements for 24 hours before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in 24-hour plasma free fatty acid profile | The outcome will determined by obtaining serial plasma free fatty acid concentration measurements for 24 hours before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in body fat mass | The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in intra-abdominal adipose tissue volume | The outcome will be measured by using magnetic resonance imaging before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in intrahepatic triglyceride content | The outcome will be measured by using magnetic resonance imaging before and after weight loss | 6 months (before and after targeted weight loss) | 
| Changes in fat free mass | The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss | 6 months (before and after targeted weight loss) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Roux-en-Y gastric bypass (RYGB), Type 2 Diabetes, Weight Loss, Low-Calorie Diet