The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

NCT ID: NCT00160056

Last Updated: 2015-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2009-04-30

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.

Objectives

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.

Conditions

Diabetes; Hypoglycemia Unawareness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Hypoglycemia

Intrerfvention is a hypoglycemic stimulus

Group Type: OTHER

Hypoglycemia

Intervention Type: PROCEDURE

Interventions

Hypoglycemia

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Smits, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

Schouwenberg BJ, Smits P, Tack CJ, de Galan BE. The effect of antecedent hypoglycaemia on beta(2)-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the beta(2)-adrenergic receptor. Diabetologia. 2011 May;54(5):1212-8. doi: 10.1007/s00125-011-2062-3. Epub 2011 Feb 6.

Reference Type: DERIVED

PMID: 21298412 (View on PubMed)

Other Identifiers

HB2-001

Identifier Type: -

Identifier Source: org_study_id