Determinants of Diabetes Remission After Gastric Bypass Surgery

The increased prevalence of obesity and type 2 diabetes (T2DM) has resulted in a surge in the
number of patients seeking surgical weight loss. Gastric bypass surgery (GBP) results in
30-40% body weight loss with resolution of T2DM in 40-80% of cases. The mechanisms by which
T2DM improves after GBP are unclear. Glycemic control occurs long before significant weight
loss, suggesting that the nature of the procedure, rather than the weight loss, is
responsible for the T2DM improvement. Recent data have singled out the role of the gut
hormones known as incretins in diabetes improvement after GBP. The current proposal will
study 1) whether the short and long term change in the gut hormone incretins after GBP
results in improved insulin secretion in response to the administration of oral and IV
glucose, in patients with diabetes undergoing GBP surgery; 2) the factors responsible for
diabetes remission - or lack of - after GBP. The investigators wish to apply our finding to
define better surgical outcome on diabetes.

Inclusion Criteria:

- Patients with a wide range of T2DM (duration, treatment modalities and control, in or
not in remission) and scheduled for GBP surgery

- Blood pressure is under at least moderate control <160/100 mmHg

- Patients can be on dyslipidemia medications but need fasting triglyceride < 600 mg/dl

- Patients without recent (last 6 months) history of cardiovascular disease (CVD)

- BMI > 35 and < 55 kg/m2 prior to GBP surgery

Exclusion Criteria:

- Active cancer

- Unstable angina

- Recent stroke

- Current therapy that may affect glucose metabolism such as glucocorticoids, HIV
medications, etc

- Active infection

- Kidney failure

- Severe liver dysfunction

- Severe respiratory or cardiac failure

- History of allergic reaction to exendin 9-39

- History of pancreatitis, history of cholelithiasis, history of alcoholism

- Presence of high triglyceride levels (>600 ng/dl)

- Pregnancy (a pregnancy test will be done prior to enrollment and prior to each
procedure in all premenopausal women)