Role of Nutrient Transit in Hyperinsulinemic Hypoglycemia

Stanford University60 enrolled

Overview

Severe hypoglycemia (low blood sugar)after gastric bypass surgery is an increasingly recognized condition, characterized by symptoms of hypoglycemia after eating and inappropriately elevated insulin concentrations that occur at the time of hypoglycemia. Severe hypoglycemia can be dangerous and debilitating and can also impact cognitive function. At the moment no medical therapies have been developed for this disorder. Determining why some but not other patients develop this condition would allow for improved prediction, prevention, and treatment approaches. The purpose of the study is to understand the physiological changes observed in those patients who undergo gastric bypass and develop symptomatic hypoglycemia.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Post-Bariatric Hypoglycemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients 18-70 years of age * Post-bariatric surgery more than 6 months prior to signing the informed consent (not required for non-surgical controls) * Documented history of hyperinsulinemic hypoglycemia (not required for post-bariatric and non-surgical controls) Exclusion Criteria: * Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug. * Participation in any clinical investigation within 4 weeks prior to dosing * History of or current insulinoma * Active infection or significant acute illness within 2 weeks prior to dosing * Female patients who are pregnant or lactating * Women of childbearing potential and not utilizing effective contraceptive methods * Inadequate end organ function as defined by: Serum creatinine \>2.0 mg/dL, alanine transaminase (ALT) and aspartate aminotransferase (AST) \> 2 x Upper Normal Limit * Allergy to test meal or medications used in the study

Outcomes

Primary Outcomes

Steady state plasma glucose (SSPG) as a measure of insulin sensitivity

This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is a one day in-person appointment lasting approximately 6 hours.

Time frame: Baseline 4-hour SSPG

Rate of gastric emptying

This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. This is an in-person appointment lasting approximately 5 hours.

Time frame: Baseline 4-hour scintigraphy procedure

Concentration of Glucagon-Like peptide 1 secretion augmentation of insulin secretion rate

This endpoint applies to the In-Clinic Phase cohorts: Post-Bariatric Hypoglycemia, Surgical Controls, Non-Surgical Controls. The blood collected from the SSPG will be stored and analyzed for the concentration of GLP-1 at multiple timepoints.

Time frame: Baseline 4-hour graded-glucose infusion

Rate of clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL)

This endpoint applies to Remote Phase participants

Time frame: 40 days

Percent time in clinically important hypoglycemia (Level 2 hypoglycemia, <54 mg/dL)

This endpoint applies to Remote Phase participants

Time frame: 40 days

Rate of arrhythmia during hypoglycemia

This endpoint applies to Remote Phase participants

Time frame: 10 days

Role of Nutrient Transit in Hyperinsulinemic Hypoglycemia

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes