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.

Category

IRB Number
20180070HU
NCT Number
NCT00992901
Open to Enrollment
Yes
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

Local Recruitment Point of Contact
Andrea Hansis-diarte
+1 (210) 617-5300
hansisdiarte@uthscsa.edu

Local Recruitment Point of Contact
Nancy Yegge
(210) 450-8696
yeggen@uthscsa.edu

Principal Investigator
Marzieh Salehi

Regulatory Point of Contact
Andrea Hansis-Diarte
(210) 617-5300
hansis@uthscsa.edu

Regulatory Point of Contact
Andrea Hansis-diarte
+1 (210) 617-5300
hansisdiarte@uthscsa.edu

Regulatory Point of Contact
Marzieh Salehi
salehi@uthscsa.edu

Regulatory Point of Contact
Nancy Yegge
(210) 450-8696
yeggen@uthscsa.edu



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)
Condition
  • Post Bariatricsurgery
  • Hypoglycemia
  • Arm Groups

    ArmDescriptionIntervention
    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

    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

    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.