Insulin resistance is
prevalent in
heart failure (HF) patients, and beta2
adrenergic receptors (beta2-AR) are involved in
glucose homeostasis. We hypothesized that beta2-AR Gln27Glu and Arg16Gly polymorphisms affect
insulin resistance in HF patients, and we explored if effects of beta2-AR polymorphisms on
glucose handling are modified by choice of
beta blocker. We studied 30 nondiabetic adults with HF and a history of
systolic dysfunction; 15 were receiving
metoprolol succinate, and 15 were receiving
carvedilol. We measured fasting
glucose,
insulin, and
insulin resistance, and we determined beta2-AR
genotypes at
codons 27 and 16. The cohort was
insulin resistant with a
mean HOMA-IR score of 3.4 (95% CI, 2.3 to 4.5; normal value, 1.0). Patients with the Glu27Glu
genotype exhibited higher
insulin and HOMA-IR compared to individuals carrying a Gln
allele (P = 0.019). Patients taking
carvedilol demonstrated lower
insulin resistance if also carrying a
wild-type allele at
codon 27 (fasting
insulin, 9.8 +/- 10.5 versus 20.5 +/- 2.1 for variant, P = 0.072; HOMA-IR, 2.4 +/- 2.7 versus 5.1 +/- 0.6, P = 0.074); those on
metoprolol succinate had high
insulin resistance irrespective of
genotype. The beta2-AR Glu27Glu
genotype may be associated with higher
insulin concentrations and
insulin resistance in patients with HF. Future studies are needed to confirm whether treatment with
carvedilol may be associated with decreased
insulin and
insulin resistance in beta2-AR
codon 27 Gln carriers.
