Clinical trial NCT00992901: Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery
Official title: Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Post Bariatricsurgery
Hypoglycemia
Keywords: gastric bypass surgery
glucose tolerance
Insulin response to meal ingestion
Gut hormone and neural response to meal ingestion
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2009-10-09
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

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

Primary outcomes:
measure: Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
timeFrame: Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Texas Diabetes Institute - University Health System
state: Texas
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System
state: Texas
Study officials:
affiliation: Marzieh Salehi
name: Marzieh Salehi, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: