The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

Study Overview
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Brief Summary
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Hypoglycaemia unawareness is a common complication in patients with type 1 diabetes and with insulin-treated type 2 diabetes of long duration. The loss of autonomic symptoms to hypoglycemia does not solely depend on loss of adrenaline responses.Differences in sensitivity to catecholamines may also be involved. Reconciling the data on β2-adrenergic receptor polymorphism to those on loss of β-adrenergic sensitivity in diabetic patients with hypoglycemia unawareness, we hypothesize that hypoglycemia unawareness is at least partly the result of desensitization of the β2-adrenergic receptor and that patients who are homozygous for arginine at codon 16 are particularly susceptible for this desensitization process, whereas patients who are homozygous for glycine at codon 16 are resistant for desensitization. Objectives To determine whether, and if so to what extent, antecedent hypoglycemia reduces β2-adrenergic sensitivity in healthy subjects with Arg16 homozygosity. To investigate whether or not healthy subjects with Gly16 homozygosity are resistant to desensitization To confirm that antecedent hypoglycemia reduces the heart rate response to isoproterenol and to assess to what extent this reduced response is mediated by impairments in baroreflex sensitivity.

Official Title
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The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity in Subjects With Homozygous Arg16 and gly16 Polymorphism of the β2-adrenergic Receptor

Conditions
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Diabetes, Hypoglycemia Unawareness

Intervention / Treatment
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* Procedure: Hypoglycemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Homozygous for Arginine at codon 16 or homozygous Gly at codon 16 No regular usage of medication other than oral contraceptives Exclusion Criteria: History of cerebrovascular, cardiovascular, or peripheral vascular disease Smoking Alcohol usage of more than 10 units per week Inability to abstain from xanthine-derivatives (coffee, tea, cola, chocolate, cacao) or alcohol for 2 days BMI above 30 kg/m2 Participation to any other trial in the preceding 3 months Ongoing disease of any kind Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hypoglycemia<br>Intrerfvention is a hypoglycemic stimulus | Procedure: Hypoglycemia<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Hypoglycemia unawareness, adrenal receptor, adrenerg respons, adrenergic beta-agonists, salbutamol