The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

NCT00160056 | Completed

• 1 other identifier: HB2-001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

Hypoglycemia unawareness; Diabetes; adrenal receptor; adrenerg respons; adrenergic beta-agonists; salbutamol

Study Arms (1)

Hypoglycemia

OTHER

Intrerfvention is a hypoglycemic stimulus

Procedure: Hypoglycemia

Interventions

Hypoglycemia PROCEDURE

Hypoglycemia

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent
• Homozygous for Arginine at codon 16 or homozygous Gly at codon 16
• No regular usage of medication other than oral contraceptives

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 21298412 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Hig1 protein, mouse

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Paul Smits, PhD, MD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 12, 2005
• Study Start: April 1, 2005
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: May 12, 2015

Record last verified: 2015-05

Locations

NL (1)