Determinants of Diabetes Remission After Gastric Bypass Surgery

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287285
• Other study ID #: AAAO1360
• Secondary ID: 1R01DK098056-01A
• Status: Completed
• Phase: Early Phase 1
• Start date: October 2014
• Est. completion date: July 2019

Study information

• Verified date: April 2020
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2019
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Exendin9
Dosed at 600 pmol/kg/min for 210 minutes.

Locations

Country	Name	City	State
United States	New York Obesity Research Center, Columbia University	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Blandine Laferrere	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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