Determinants of Diabetes Remission After Gastric Bypass Surgery

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Long Term Change of GLP-1 Insulinotropic Effect After GBP Surgery

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Exendin9


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exendin9<br>Longitudinal study of insulin secretion and sensitivity in patients with type 2 diabetes before and after gastric bypass surgery. | Drug: Exendin9<br>* Dosed at 600 pmol/kg/min for 210 minutes.<br>* Other names: Exendin(9-39);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta Cell Sensitivity (BCS) | Oral glucose tolerance test (OGTT) will be used to calculate BCS Graded glucose infusion with arginine (GGI) will be used to calculate BCS | at 2 years post GBP surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion Rate (ISR) after OGTT | An oral glucose tolerance test (OGTT) will be used to estimate ISR in subjects before and up to 2 years after GBP | 2 years post GBP surgery | 
| Insulin Secretion Rate (ISR) after GGI | A graded glucose infusion with arginine (GGI) will be used to estimate ISR in subjects before and up to 2 years after GBP | 2 years post GBP surgery | 
| Maximal Beta Cell Function | The effect of a graded glucose infusion with arginine (GGI) on insulin secretion rate (ISR) will be measured in subjects before and up to 2 years after GBP | 2 years post GBP surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Gastric Bypass Surgery, Exendin9