The Effects of Antecedent Hypoglycemia or Exercise on the Response of the Brain to Subsequent Hypoglycemia

Study Overview
=================
Brief Summary
-----------------
The studies proposed in this application seek to use non-invasive techniques to examine the impact of repeated hypoglycemia on the brain.

Detailed Description
-----------------
The studies proposed in this application seek to use non-invasive techniques to examine the impact of repeated hypoglycemia on the brain. During the past decade many studies have shown that appropriate magnetic resonance imaging (MRI) methods may be used to assess alterations in brain regional activation in response to external stimuli or tasks. Thus, this non-invasive technique will enhance our ability to learn more about brain function, during hypoglycemia and may delineate information about the role of the brain in hypoglycemia associated autonomic dysfunction.

Official Title
-----------------
The Effects of Antecedent Hypoglycemia or Exercise on the Response of the Brain to Subsequent Hypoglycemia

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Procedure: Hyperinsulinemic euglycemic clamp with fMRi
* Procedure: Hyperinsulinemic hypoglycemic clamp study with fMRi


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female subjects aged 18-45 Type 1 diabetes mellitus patients aged 18-45 Body Mass Index 21-38 kg/m2 Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities and an EKG stress test. Female volunteers of childbearing potential will undergo HCG pregnancy test. Only women who are not pregnant will participate in the study. Diabetic Subjects: HBA1C= 5.5-11.0% Duration of Type 1 Diabetes > 3 yr Normal bedside autonomic function Exclusion Criteria: All Subjects Prior or current history of poor health Abnormal results following screening tests Pregnancy Subjects unable to give voluntary informed consent Subjects with a recent medical illness Subjects with a history of hypertension, heart disease or cerebrovascular disease Subjects with known liver or kidney disease Subjects with recent weight loss or consuming a low carbohydrate diet Subjects taking steroids Subjects taking beta-blockers Subjects on anticoagulant drugs, anemic or with known bleeding diatheses Evidence of diabetic neuropathy, autonomic neuropathy, proteinuria, extensive background or proliferative retinopathy, hypertension, or cardiovascular disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Hyperinsulinemic euglycemic clamp with fMRi | Procedure: Hyperinsulinemic euglycemic clamp with fMRi<br>* Hyperinsulinemic euglycemic clamp on day 1 with morning fMRi<br>|
| Experimental: 2<br>Hyperinsulinemic hypoglycemic clamp with fMRI | Procedure: Hyperinsulinemic hypoglycemic clamp study with fMRi<br>* Hyperinsulinemic hypoglycemic clamp on day1 with fMRi in morning<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRi scans |  | 1 day | 

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