Post-Gastric Bypass Hypoglycemia

Study Overview
=================
Brief Summary
-----------------
Post-gastric bypass hyperinsulinemic hypoglycemia is a recently described disorder occurring in some patients after gastric bypass surgery for obesity. The pathogenesis is incompletely understood but involves a robust insulin response to ingested carbohydrate. The resultant hyperinsulinemia sometimes produces hypoglycemia with neuroglycopenia, confusion and even loss of consciousness. Various treatments have been recommended including low carbohydrate diets, coingestion of the medication acarbose with carbohydrate containing meals, partial pancreatectomy and even total pancreatectomy. None is completely satisfactory. We propose to test two new potential treatments. Using a design with random assignment of three conditions we plan to compare, in 10 patients with post-gastric bypass hyperinsulinemic hypoglycemia, a high carbohydrate test meal (control condition), a high carbohydrate test meal after pre-treatment with rapid acting aspart insulin (insulin condition), and a high fructose, low glucose test meal with carbohydrate and caloric content similar to the control meal (fructose condition).

Detailed Description
-----------------
Post-gastric bypass hyperinsulinemic hypoglycemia is a recently described disorder occurring in some patients after gastric bypass surgery for obesity. The pathogenesis is incompletely understood but involves a robust insulin response to ingested carbohydrate. The resultant hyperinsulinemia sometimes produces hypoglycemia with neuroglycopenia, confusion and even loss of consciousness. Various treatments have been recommended including low carbohydrate diets, coingestion of the medication acarbose with carbohydrate containing meals, partial pancreatectomy and even total pancreatectomy. None is completely satisfactory. We propose to test two new potential treatments. Using a design with random assignment of three conditions we plan to compare, in 10 patients with post-gastric bypass hyperinsulinemic hypoglycemia, a high carbohydrate test meal (control condition), a high carbohydrate test meal after pre-treatment with rapid acting aspart insulin (insulin condition), and a high fructose, low glucose test meal with carbohydrate and caloric content similar to the control meal (fructose condition). The hypothesis to be tested are 1) pretreatment with aspart insulin will prevent, or at least reduce, the occurrence of hypoglycemia and 2) substitution of fructose for glucose in the test meal will prevent, or at least reduce, the occurrence of hypoglycemia. Plasma glucose and serum insulin will be sampled before and for four hours after the three test conditions. The primary study endpoint will be the occurrence or not of plasma glucose < 60 mg/dL after the test meals. The control meal will be compared to the insulin pre-treated test meal and, in a separate comparison, to the fructose test meal. Secondary endpoints will be comparisons between the control and active treatments in peak postprandial serum insulin, peak postprandial plasma glucose, nadir postprandial plasma glucose, and the 4-hr longitudinal course of plasma glucose measurements.

Official Title
-----------------
Prevention of Hypoglycemia in Patients With Post-Gastric Bypass Hyperinsulinemic Hypoglycemia

Conditions
-----------------
Hyperinsulinemic Hypoglycemia

Intervention / Treatment
-----------------
* Other: high carbohydrate test meal
* Other: high carbohydrate test meal after pre-treatment with rapid acting aspart insulin
* Other: high fructose , low glucose test meal with carbohydrate and caloric content similar to the control meal


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be at least 21 years of age History of postprandial hypoglycemia with neuroglycopenia occurring one year or more after gastric bypass surgery History of spontaneous correction of hypoglycemia Normal fasting plasma glucose and serum insulin after a carbohydrate containing mixed meal, demonstration of serum insulin > 50u/UL and plasma glucose < 50mg/dL Exclusion Criteria: Under 21 years of age

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: a high carbohydrate test meal (control condition)<br>a high carbohydrate test meal (control condition) | Other: high carbohydrate test meal<br> <br> Other: high carbohydrate test meal after pre-treatment with rapid acting aspart insulin<br> <br> Other: high fructose , low glucose test meal with carbohydrate and caloric content similar to the control meal<br> <br> |
| Active Comparator: high carbohydrate test meal after pre-treatment<br>a high carbohydrate test meal after pre-treatment with rapid acting aspart insulin (insulin condition) | Other: high carbohydrate test meal<br> <br> Other: high carbohydrate test meal after pre-treatment with rapid acting aspart insulin<br> <br> Other: high fructose , low glucose test meal with carbohydrate and caloric content similar to the control meal<br> <br> |
| Active Comparator: high fructose low glucose test meal<br>high fructose , low glucose test meal with carbohydrate and caloric content similar to the control meal (fructose condition) | Other: high carbohydrate test meal<br> <br> Other: high carbohydrate test meal after pre-treatment with rapid acting aspart insulin<br> <br> Other: high fructose , low glucose test meal with carbohydrate and caloric content similar to the control meal<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary study endpoint will be occurrence or not of plasma glucose < 60 mg/dL during the 4 hours after the test meal (binary endpoint). | The primary study endpoint will be occurrence or not of plasma glucose < 60 mg/dL during the 4 hours after the test meal (binary endpoint). | 4 hours after meal | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hyperinsulinemic hypoglycemia