Obesity, Type 2 Diabetes
Conditions
Keywords
Obesity, Roux-en-Y gastric bypass (RYGB), Type 2 Diabetes, Weight Loss, Low-Calorie Diet
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.
Interventions
PROCEDURERoux-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.
BEHAVIORALLow-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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in hepatic insulin sensitivity | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in skeletal muscle and adipose tissue insulin sensitivity | 6 months (before and after targeted weight loss) | The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss. |
| Changes in Beta-cell function | 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. |
| Changes in glucose kinetics (glucose concentration and rate of appearance into the systemic circulation) in response to mixed-meal ingestion | 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 |
| Changes in 24-hour plasma glucose profile | 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 |
| Changes in 24-hour plasma insulin profile | 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 |
| Changes in 24-hour plasma free fatty acid profile | 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 |
| Changes in body fat mass | 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 |
| Changes in intra-abdominal adipose tissue volume | 6 months (before and after targeted weight loss) | The outcome will be measured by using magnetic resonance imaging before and after weight loss |
| Changes in intrahepatic triglyceride content | 6 months (before and after targeted weight loss) | The outcome will be measured by using magnetic resonance imaging before and after weight loss |
| Changes in fat free mass | 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 |
Countries
United States
Outcome results
None listed