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.

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