Type 2 Diabetes, Obesity
Conditions
Keywords
Roux-en-Y gastric bypass
Brief summary
The purpose of this study is to investigate small intestinal remodeling and reprogramming of glucose metabolism in patients with Type 2 Diabetes Mellitus (T2DM) who undergo laparoscopic Roux-en-Y Gastric Bypass (RYGB). Our specific goal is to determine if the gene and protein expression levels of GLUT-1 are up regulated in the Roux limb and whether this is a major mechanism for the remission of T2DM following RYGB. The two aims of the study are: 1) to demonstrate that the basement membrane glucose transporter 1 (GLUT-1) is upregulated in the Roux limb following RYGB, and 2) to demonstrate that the upregulation of GLUT-1 is a major mechanism for the improvement in glycemic control observed in T2DM patients undergoing RYGB.
Interventions
OTHERMix Nutrient Meal
Before Surgery: Subjects will have a visit where they will have a mixed nutrient stimulation test. They will be asked to fast for 12 hours prior to this visit (except water). During the visit they will drink an 8 ounce mixed nutrient liquid meal in 5 minute intervals over 20 minutes. During this visit a catheter will be placed in a vein in their arm for blood sample collections. A total of 50 ml of blood will be collected, (10 ml before drinking the mixed nutrient drink, at 30 minutes, at 60 minutes, at 90 minutes and 120 minutes after the mixed nutrient drink).
OTHERlabs
Fasting Plasma Glucose (FPG) and insulin will be added to the standard pre-operative labs.
OTHERBiopsy
Intra-operatively: Subjects will undergo a standard laparoscopic Roux-en-Y Gastric Bypass (RYGB). During the surgery a 2cm tissue sample of the Roux limb will be taken by the doctor and frozen.
OTHERSecond Mix Nutrient Meal
2 months post-operatively a second mixed nutrient stimulation test will be performed following the same process used pre-operatively.
OTHERSecond biopsy
. Patients will also be scheduled to undergo a second upper endoscopy and a 2cm biopsy of the Roux limb will be taken by the doctor and frozen in liquid nitrogen.
DEVICEPET/CT
Lastly, subjects will have a positron emission tomography/computed tomography (PET/CT) scan with Fluorodeoxyglucose (FDG) to evaluate the glucose in the Roux limb after surgery.
Sponsors
Society of American Gastrointestinal and Endoscopic Surgeons
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Type 2 Diabetes Mellitus 2. Age between 18 and 65 years of age 3. BMI \> 35kg/m² 4. Diagnosis of gastritis, esophagitis, ulcer, or other mucosal abnormality discovered at routine preoperative upper endoscopy, requiring follow-up endoscopy in the post-operative period.
Exclusion criteria
1. Patients undergoing revision from another bariatric procedure to RYGB 2. Presence of a seizure disorder (GLUT-1 deficiency syndrome) 3. Use of Tricyclic antidepressants 4. Use of tobacco products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Elevated Glut-1 gene and protein expression levels | 2 months | Gene and protein expression levels of GLUT-1 will be analyzed from the specimens obtained intra-operatively (baseline) and at 2 months post-operatively to determine if levels are significantly elevated above baseline. Quantitative real-time PCR and Western blot techniques will be utilized as described in C below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glut-1 level change in fasting glucose | 2 months | Change in GLUT-1 levels will be correlated with changes in fasting glucose, mixed meal stimulation test, and homeostasis model assessment (HOMA). Secondly, at 2 months post-operatively, whole-body positron emission tomography/computed tomography (PET/CT) scanning with Fluorodeoxyglucose (FDG) will be performed to evaluate glucose uptake and utilization in the Roux limb. |
Outcome results
None listed