Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Exendin-(9-39)
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
  • Drug: Exendin-(9-39)
    A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
    Other names:
    • No other name for Exendin-(9-39)
Experimental
atropine
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
  • Drug: Atropine
    A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
    Other names:
    • Atropine sulfate
Experimental
GLP-1 and GIP
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
  • Drug: GLP-1 and GIP
    A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
    Other names:
    • No other names for GLP-1 and GIP.

Recruiting Locations

South Texas Veterans Health Care System
San Antonio, Texas 78229
Contact:
Marzieh Salehi
210-567-6691
salehi@uthscsa.edu

Texas Diabetes Institute - University Health System
San Antonio, Texas 78207
Contact:
Andrea Hansis-Diarte, MPh
210-567-6691
hansisdiarte@uthscsa.edu

More Details

NCT ID
NCT00992901
Status
Recruiting
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Marzieh Salehi, MD MS
210-567-6691
salehi@uthscsa.edu

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.