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Determinants of Diabetes Remission After Gastric Bypass Surgery

Early Phase 1
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT02287285
Lead Sponsor
Blandine Laferrere
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Exendin9Exendin9Longitudinal study of insulin secretion and sensitivity in patients with type 2 diabetes before and after gastric bypass surgery.
Primary Outcome Measures
NameTimeMethod
Beta Cell Sensitivity (BCS)at 2 years post GBP surgery

Oral glucose tolerance test (OGTT) will be used to calculate BCS Graded glucose infusion with arginine (GGI) will be used to calculate BCS

Secondary Outcome Measures
NameTimeMethod
Insulin Secretion Rate (ISR) after OGTT2 years post GBP surgery

An oral glucose tolerance test (OGTT) will be used to estimate ISR in subjects before and up to 2 years after GBP

Insulin Secretion Rate (ISR) after GGI2 years post GBP surgery

A graded glucose infusion with arginine (GGI) will be used to estimate ISR in subjects before and up to 2 years after GBP

Maximal Beta Cell Function2 years post GBP surgery

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

Trial Locations

Locations (1)

New York Obesity Research Center, Columbia University

🇺🇸

New York, New York, United States

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