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The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

This study has been completed.
Information provided by (Responsible Party):
Radboud University Identifier:
First received: September 9, 2005
Last updated: May 8, 2015
Last verified: May 2015

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.


  1. To determine whether, and if so to what extent, antecedent hypoglycemia reduces β2-adrenergic sensitivity in healthy subjects with Arg16 homozygosity.
  2. To investigate whether or not healthy subjects with Gly16 homozygosity are resistant to desensitization
  3. 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.

Condition Intervention
Hypoglycemia Unawareness
Procedure: Hypoglycemia

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Participant)
Primary Purpose: Diagnostic
Official Title: The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity in Subjects With Homozygous Arg16 and gly16 Polymorphism of the β2-adrenergic Receptor

Resource links provided by NLM:

Further study details as provided by Radboud University:

Enrollment: 16
Study Start Date: April 2005
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Intrerfvention is a hypoglycemic stimulus
Procedure: Hypoglycemia


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
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Please refer to this study by its identifier: NCT00160056

Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
Principal Investigator: Paul Smits, PhD, MD Radboud University
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Radboud University Identifier: NCT00160056     History of Changes
Other Study ID Numbers: HB2-001
Study First Received: September 9, 2005
Last Updated: May 8, 2015

Keywords provided by Radboud University:
Hypoglycemia unawareness
adrenal receptor
adrenerg respons
adrenergic beta-agonists

Additional relevant MeSH terms:
Glucose Metabolism Disorders
Metabolic Diseases
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on April 21, 2017