Determinants of Diabetes Remission After Gastric Bypass Surgery

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Exendin9

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York Obesity Research Center, Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Blandine Laferrere
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Blandine Laferrere, MD, New York Obesity Nutrition Research Center, Columbia University

Publications and helpful links

General Publications

• Prasad M, Mark V, Ligon C, Dutia R, Nair N, Shah A, Laferrere B. Role of the Gut in the Temporal Changes of beta-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission. Diabetes Care. 2022 Feb 1;45(2):469-476. doi: 10.2337/dc21-1270.
• Shah A, Holter MM, Rimawi F, Mark V, Dutia R, McGinty J, Levin B, Laferrere B. Insulin Clearance After Oral and Intravenous Glucose Following Gastric Bypass and Gastric Banding Weight Loss. Diabetes Care. 2019 Feb;42(2):311-317. doi: 10.2337/dc18-1036. Epub 2018 Dec 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2014
• Primary Completion (ACTUAL): August 1, 2017
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: November 6, 2014
• First Posted (ESTIMATE): November 10, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 21, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus; Gastric Bypass Surgery; Exendin9
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: AAAO1360; 1R01DK098056-01A1 (NIH); 1F32DK113747-01A1 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 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..
• IPD Sharing Access Criteria: contact the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No