Comparison Between Hypoglycemic Counter Regulatory Responses in Type 1 Diabetics vs Control Subjects

Study Overview
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Brief Summary
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This study compares the hypoglycemic counter regulatory response in type 1 diabetics and in healthy control subjects with and without antecedent hypoglycemia

Detailed Description
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Iatrogenic hypoglycemia is one of the main limiting factors for optimal glycemic management of diabetes. It causes recurrent morbidity in most people with type 1 diabetes and in many patients with type 2 diabetes and can be fatal. Episodes of hypoglycemia impair physiologically protective mechanism in subsequent episodes of hypoglycemia. This phenomenon is known as hypoglycemia-associated autonomic failure (HAAF), the clinical syndromes of defective glucose counter regulation and hypoglycemia unawareness.

Official Title
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A Comparison Between Counter Regulatory Responses in Type 1 Diabetic Patients Versus Healthy Control Subjects With and Without Antecedent Hypoglycemia

Conditions
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Hypoglycemia, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: Glucose clamp technique


Participation Criteria
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Eligibility Criteria
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Type 1 diabetics Inclusion Criteria: More than 5 years of disease duration HbA1c 42-86 mmol/L No known HAAF BMI 22-28 Written consent Exclusion Criteria: Other disease than diabetes f.x epilepsy, ischemic heart disease or heart rhythm disturbance Medication f.x beta-blockade, steroids, psychotropics Smoking Drug abuse Control subjects Inclusion Criteria: BMI 22-28 Written consent Exclusion Criteria: Diseases f.x diabetes, epilepsy, ischemic heart disease or heart rhythm disturbance Medication f.x beta-blockade, steroids, psychotropics Smoking Drug abuse

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 9 diabetic subjects and 9 healthy control subjects will be randomized to undergo either first day 1 + day 2 (two consecutive episode of hypoglycemia) or first day 3 + day 4 (one episode of hypoglycemia).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single episode of hypoglycemia<br>Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours | Other: Glucose clamp technique<br>* Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose<br>|
| Active Comparator: Two episodes of hypoglycemia<br>Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours | Other: Glucose clamp technique<br>* Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity before, during hypoglycemia and after recovery from hypoglycemia on day 2 (one episode of hypoglycemia) compared with day 4 (two consecutive episodes of hypoglycemia). Insulin sensitivity is measured as M-value derived from the Glucose Infusion Rate (GIR) during a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp | Day 2 and day 4 (T=60 minutes - T=240 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hormonal counter regulatory response to hypoglycemia | Hormonal counter regulatory response (epinephrine, norepinephrine, glucagon, cortisol, ghrelin etc.) measured regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp | Day 2 and day 4 (T=0 minutes, T=30, T=40, T=50, T=120, T=130, T=140, T160, T=170, T=180, T=210, T=220, T=230, T=390, T=400 and T=410 | 
| Symptoms during hypoglycemia | Using the Edinburgh Hypoglycemia Scale (symptom scale) we will interview the subjects regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp | Day 2 and day 4 (T=0 minutes - T=420 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoglycemia-Associated Autonomic Failure (HAAF)