Longitudinal study of beta cell function up to 2 years after GBP surgery. Evaluation of the role of endogenous glucagon-like peptide-1 (GLP-1).

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)

The data generated from this study will be presented at national or international conferences and published in a timely fashion. All final peer-reviewed manuscripts that arise from this study will be submitted upon acceptance for publication to the digital archive NIH National Library of Medicine PubMed Central (PMC) database, according to the NIH Policy on Enhancing Public Access to Archived Publications Resulting from NIH Funded Research. Any data released for publication will be for research purposes only and will not include identifiable data on any of the participants.

Wherever applicable, fully de-identified data will be deposited to appropriate public repositories, following the Federal Health Insurance Privacy and Portability Act (HIPAA). This will occur no longer than 6 months after publications of the data generated by this record, or, 18 months after completion of the funding period, should no data had been published..

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