Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes (RBD-T2D)

• ClinicalTrials.gov Identifier: NCT02207777
• Recruitment Status: Active, not recruiting
• First Posted: August 4, 2014
• Last Update Posted: April 12, 2022
• Sponsor: Washington University School of Medicine
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Type 2 Diabetes	Procedure: Roux-en-Y gastric bypass surgery; Behavioral: Low-calorie diet	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes
• Actual Study Start Date: August 2014
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: February 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Roux-en-Y gastric bypass (RYGB); 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; A surgical procedure to help subjects lose approximately 16-18% (with a range of 16-25%) of their body weight.
Active Comparator: Low-calorie diet; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Changes in hepatic insulin sensitivity [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.

Secondary Outcome Measures :

1. Changes in skeletal muscle and adipose tissue insulin sensitivity [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.
2. Changes in Beta-cell function [ Time Frame: 6 months (before and after targeted weight loss) ]
   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.
3. Changes in glucose kinetics (glucose concentration and rate of appearance into the systemic circulation) in response to mixed-meal ingestion [ Time Frame: 6 months (before and after targeted weight loss) ]
   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
4. Changes in 24-hour plasma glucose profile [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be determined by obtaining serial plasma glucose concentration measurements for 24 hours before and after weight loss
5. Changes in 24-hour plasma insulin profile [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will determined by obtaining serial plasma insulin concentration measurements for 24 hours before and after weight loss
6. Changes in 24-hour plasma free fatty acid profile [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will determined by obtaining serial plasma free fatty acid concentration measurements for 24 hours before and after weight loss
7. Changes in body fat mass [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss
8. Changes in intra-abdominal adipose tissue volume [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be measured by using magnetic resonance imaging before and after weight loss
9. Changes in intrahepatic triglyceride content [ Time Frame: 6 months (before and after targeted weight loss) ]
   The outcome will be measured by using magnetic resonance imaging before and after weight loss
10. Changes in fat free mass [ Time Frame: 6 months (before and after targeted weight loss) ]
    The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Samuel Klein, MD; Washington University School of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yoshino M, Kayser BD, Yoshino J, Stein RI, Reeds D, Eagon JC, Eckhouse SR, Watrous JD, Jain M, Knight R, Schechtman K, Patterson BW, Klein S. Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes. N Engl J Med. 2020 Aug 20;383(8):721-732. doi: 10.1056/NEJMoa2003697.

van Vliet S, Koh HE, Patterson BW, Yoshino M, LaForest R, Gropler RJ, Klein S, Mittendorfer B. Obesity Is Associated With Increased Basal and Postprandial β-Cell Insulin Secretion Even in the Absence of Insulin Resistance. Diabetes. 2020 Oct;69(10):2112-2119. doi: 10.2337/db20-0377. Epub 2020 Jul 10.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02207777
• Other Study ID Numbers: 201403065; 1R01DK101578 ( U.S. NIH Grant/Contract )
• First Posted: August 4, 2014
• Last Update Posted: April 12, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:

Obesity; Roux-en-Y gastric bypass (RYGB); Type 2 Diabetes; Weight Loss; Low-Calorie Diet

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Weight Loss; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Body Weight Changes