The β ₂ adrenergic receptor GIn27Glu polymorphism affects insulin resistance in patients with heart failure: Possible modulation by choice of beta blocker

Insulin resistance is prevalent in heart failure (HF) patients, and beta2 adrenergic receptors (β ₂-AR) are involved in glucose homeostasis. We hypothesized that β ₂-AR Gln27Glu and Arg16Gly polymorphsms affect insulin resistance in HF patients, and we explored if effects of β ₂-AR polymorphisms on glucose hadling 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 β ₂-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 β ₂-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 β ₂-AR codon 27 Gln carriers.