The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00160056
Recruitment Status : Completed
First Posted : September 12, 2005
Last Update Posted : May 12, 2015
Information provided by (Responsible Party):
Radboud University

Brief Summary:

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 or disease Intervention/treatment Phase
Diabetes Hypoglycemia Unawareness Procedure: Hypoglycemia Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (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
Study Start Date : April 2005
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arm Intervention/treatment
Intrerfvention is a hypoglycemic stimulus
Procedure: Hypoglycemia

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00160056

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

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
First Posted: September 12, 2005    Key Record Dates
Last Update Posted: May 12, 2015
Last Verified: May 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