A Role for FGF21 in Postprandial Nutrient Homeostasis After RYGB (FGB)

Bariatric surgery markedly improves glycemic control in persons with Type 2 Diabetes (T2D). Roux-en-Y gastric bypass (RYGB), a procedure that bypasses the upper gastrointestinal (UGI) tract, results in greater rates of diabetes resolution compared to methods that leave the UGI tract intact. Studies suggest that mechanisms beyond weight-loss account for the superiority of RYGB compared to other surgical methods. These weight-loss independent metabolic effects may involve increased postprandial production and release of nutrition- responsive hormones. Fibroblast growth factor 21 (FGF21) is a nutrition-adaptive hormone with the potential to alleviate symptoms of diabetes and obesity. Preliminary data therefore suggest that RYGB surgery may alter postprandial FGF21 regulation which could be important for achieving post-meal nutrient homeostasis. Therefore, the goal of this study is to test how nutrient content of the meal affects FGF21 concentrations before and after weight loss induced by RYGB or very low calorie diet (VLCD) therapy. The importance of FGF21 for glucose, insulin, triglyceride, and adipose tissue and muscle metabolism in these two groups will also be tested.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Procedure: Roux-en-Y gastric bypass surgery; Behavioral: Very low-calorie diet

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Beth Henk; Phone Number: 314-362-8250; Email: bhenk@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Beth Henk
      • Contact: Beth Henk; Phone Number: 314-362-8250; Email: bhenk@wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Surgery Group (RYGB):

• Males and Females
• Scheduled for RYGB surgery
• Body Mass Index 35-55 kg/m²
• Without Type 2 Diabetes (T2D)

VLCD group:

• Males and Females
• Body Mass Index 35-55 kg/m²
• Without Type 2 Diabetes (T2D)

Exclusion Criteria:

Surgery Group (RYGB):

• Regular use of tobacco products
• Previous intestinal resection
• Pregnant or breastfeeding
• Evidence of significant organ system dysfunction or disease other than obesity and T2D
• Use of any medication that might, in the opinion of the investigator, affect metabolic function
• Exercise ≥90 minutes per week
• Use or past use of hormone replacement therapy within the past 6 months

VLCD Group:

• Regular use of tobacco products
• Previous intestinal resection
• Pregnant or breastfeeding
• Evidence of significant organ system dysfunction or disease other than obesity and T2D
• Use of any medication that might, in the opinion of the investigator, affect metabolic function
• Exercise ≥90 minutes per week
• Use or past use of hormone replacement therapy within the past 6 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RYGB group; Subjects in this group are scheduled to undergo Roux-en-Y gastric bypass surgery and will be assessed after 16-18% weight-loss	Procedure: Roux-en-Y gastric bypass surgery; A bariatric surgery procedure which will help individuals achieve 16-18% weight loss
Active Comparator: VLCD Group; Subjects in this group will participate in a very low-calorie diet intervention to obtain a 16-18% weight loss.	Behavioral: Very low-calorie diet; Subjects will meet with a dietitian and/or behaviorist over 4-6 months to lose 16-18% of their body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial FGF21 plasma concentrations	Concentrations of FGF21 protein will be measured in plasma after consuming a high glucose meal or a high fat meal, before and after surgery or low calorie diet.	9 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Samuel Klein, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2017
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Very low calorie diet; Roux-en-Y gastric bypass (RYGB); Fibroblast growth factor 21 (FGF21)
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 201612107; UL1TR000448 (U.S. NIH Grant/Contract); KL2TR000450 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No