Laparoscopic Gastric Bypass for Type 2 Diabetes Mellitus With Body Mass Index (BMI) < 35

The primary endpoint will be the reduction of HbA1c and secondary endpoints will be multiple
associated parameters as listed below. A group of 50 subjects with medically documented T2DM
and BMI of 26-35 will undergo standard laparoscopic RYGB. Prior to surgery, the subjects
will undergo the standard pre-operative work up required for conventional bariatric surgery.
This includes full history and physical exam, medical/cardiac clearances as needed,
nutrition consultation and a gastrointestinal consultation for upper endoscopy. After
thorough explanation an approved informed consent will be signed. Baseline parameters, as
listed below, will be measured for each subject to identify possible complications of
diabetes prior to the surgical intervention..

After surgery perioperative complications will be monitored and required modifications of
diabetes management advised. Followed up measurements at 1, 3, 6, 12, and 24 months is
consistent with standard clinical practice guidelines. Data analysis will be ongoing to
observe the effects of the surgical intervention on glucose homeostasis.

- Baseline parameters

- History and Physical Exam

- Weight/BMI/ body composition with the Tanita 310.

- Waist Circumference

- Blood Pressure

- CBC

- HbA1c

- Fasting glucose

- Vitamin B6, B12, Folate,and Iron status

- Lipid Profile -total cholesterol, HDL, LDL, triglyceride

- Fasting Insulin and C-peptide

- Stimulated C-peptide

- EKG

- Retinal exam

- Urinalysis (assess for proteinuria and microalbuminuria)

- Comprehensive foot exam

- Medications and dosage

- Quality of Life Score (SF-36)

- Carotid ultrasound (intima-media thickness)

Follow-up:

4 Weeks:

- Physical Examination, wound check, Body weight, BMI,

- Glucose Diary (pre and postprandial glucose levels as required)

- Insulin and C-peptide

- Lipid profile

- Medication use

3 Months, 6 months,

Same as above plus:

- HbA1c

- Vitamin levels and iron status

- Retinal exam

- Annually the baseline measurements will be repeated

Inclusion Criteria:

Adult males and females who meet the following inclusion criteria will be offered the
opportunity to participate in the study:

1. Diagnosis of type 2 Diabetes Mellitus (T2DM) confirmed by the following criteria:

1. normal or high C-peptide level (> 0.9 ng/ml) to exclude type 1 Diabetes Mellitus

2. positive glucagon test to confirm T2DM

3. fasting plasma glucose of 126 mg/dl or more on at least two occasions

2. Body mass index (BMI) 26 kg/m2 or greater, and less than 35 kg/m2

3. History of T2DM for not longer than 8 years, as long-standing disease beyond 8 years
correlates with failure to achieve diabetes resolution after gastric bypass

4. No contraindication for surgery or general anesthesia as determined by a
multidisciplinary bariatric surgery team (surgeon, anesthesiologist, internist,
dietitian, psychologist)

5. Between 18 and 65 year of age

6. Able to provide informed consent

7. If a female with reproductive potential, she has to agree to use a reliable method of
birth control for at least one year from the date of surgery

Exclusion Criteria

Subjects who meet any of the following exclusion criteria will not be eligible to
participate in the study:

1. Enrollment in another clinical study, which involves an investigational drug

2. Diagnosis of type 1 Diabetes Mellitus or other genetic forms of Diabetes Mellitus

3. Significant renal failure of chronic liver disease (except NAFLD)

4. Major psychological disorders

5. Pregnancy - all female subjects will have serum beta-hCG prior to operation, and must
use birth control of their choice to avoid pregnancy during the first year after
surgery

6. Previous gastric or esophageal surgery

7. Immunosuppressive drugs including corticosteroids

8. Coagulopathy defined as an INR > 1.5 or platelet count < 50,000/µl

9. Anemia defined as a Hb <10.0 g/dl

10. Inflammatory bowel diseases or other medical condition that would serve as a
contraindication to gastric bypass (eg. celiac sprue, pancreatic insufficiency)

11. A severe concurrent illness that is likely to limit life or require extensive
systemic treatment (e.g. cancer)

12. A pre-existing major complication of diabetes:

1. unstable, proliferative retinopathy

2. severe autonomic cardiac neuropathy or intestinal neuropathy

3. Myocardial infarction within the previous year, current unstable angina, or
poorly-controlled congestive heart failure (Stage III)