Schouwenberg BJ, Smits P, Tack CJ et al.
Radbound University Nijmegen Medical Centre, The Netherlands.
Diabetologia 2011;54:1212–8.
Editor’s note: Although it has been observed that recurrent hypoglycemic episodes can result in impaired glucose counter-regulatory defenses and reduced hypoglycemic awareness (Diabetes 2008;57:3169–76), it is also well recognized that the degree to which such impaired awareness of hypoglycemia occurs is variable from individual to individual, suggesting there may be a genetic component to susceptibility. It was recently discovered that the prevalence of hypoglycemia unawareness was partially determined by a single nucleotide polymorphism (SNP) in the gene encoding the β2-adrenergic receptor (ADRB2; Pharmacogenet Genomics 2008;18:369–72). Patients who were homozygous glycine (GlyGly) at codon 16 of the ADRB2 were more likely to report hypoglycemia unawareness than those who were heterozygous arginine/glycine (ArgGly) or homozygous for arginine (ArgArg). The SNP occurring at position 46 of ADRB2, encoding for arginine or glycine at the N-terminus (codon 16) of the ADRB2, may determine the extent to which the β2-adrenergic receptors lose sensitivity when continually stimulated.