Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery

NCT ID: NCT00992901

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2027-08-31

Brief Summary

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls.

Detailed Description

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls

Conditions

Post Bariatricsurgery; Hypoglycemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Exendin-(9-39)

To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

Group Type: EXPERIMENTAL

Exendin-(9-39)

Intervention Type: DRUG

A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

atropine

To evaluate the effect of neural activation on insulin secretion and glucose metabolism

Group Type: EXPERIMENTAL

Atropine

Intervention Type: DRUG

A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism

GLP-1 and GIP

to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Group Type: EXPERIMENTAL

GLP-1 and GIP

Intervention Type: DRUG

A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Interventions

Exendin-(9-39)

A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

Intervention Type: DRUG

Atropine

A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism

Intervention Type: DRUG

GLP-1 and GIP

A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Intervention Type: DRUG

Other Intervention Names

No other name for Exendin-(9-39); Atropine sulfate; No other names for GLP-1 and GIP.

Eligibility Criteria

Inclusion Criteria

• Hypoglycemic RYGB patients with documented blood glucose level <50 mg/dl
• Asymptomatic individuals with bariatric surgery
• Healthy non-surgical patients with no personal history of diabetes
• Subjects must physically be able to come to our clinical research center at Cedars-Sinai Medical Center

Exclusion Criteria

• Active heart, lung, liver, gastrointestinal or kidney disease; unable to give informed consent; pregnancy; uncontrolled high blood pressure or high cholesterol; significant anemia (hemoglobin <11g/dL); prisoners or institutionalized individuals; type 2 diabetes melitis; development of any serious medical or psychiatric illness during recruitment or studies;
• RYGB patients will also be disqualified if they have gastric outlet obstruction or severe diarrhea
• Healthy non-surgical patients with personal history of diabetes

For administration of atropine, the following exclusions also apply:

• History of glaucoma
• Uncontrolled hypertension (any subjects with BP>140/90 and history of dyslipidemia
• Taking any medication that might interact with atropine and cannot be stopped will be excluded from the study)
• Myasthenia gravis
• Brain pathology
• Enlarged prostate in men

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marzieh Salehi, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Marzieh Salehi

Locations

Texas Diabetes Institute - University Health System

San Antonio, Texas, United States

Site Status: RECRUITING

South Texas Veterans Health Care System

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marzieh Salehi, MD MS

Role: CONTACT

salehi@uthscsa.edu

210-567-6691

Jennifer Foster, MSN

Role: CONTACT

fosterj6@uthscsa.edu

210-450-8696

Facility Contacts

Jennifer Foster, MSN

Role: primary

fosterj6@uthscsa.edu

210-450-8696

Marzieh Salehi, MD, MS

Role: backup

salehi@uthscsa.edu

210-567-6691

Marzieh Salehi

Role: primary

salehi@uthscsa.edu

210-567-6691

Jennifer Foster, MSN

Role: backup

fosterj6@uthscsa.edu

210-450-8696

Other Identifiers

DK083554

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

18-070H

Identifier Type: -

Identifier Source: org_study_id