title: The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker.
abstract: 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.
authors.affiliation: University of Wisconsin School of Pharmacy, Pharmacy Practice Division, Madison, WI 53705-2222, USA. ovardeny@pharmacy.wisc.edu
authors.forename: Orly
authors.initials: O
authors.lastname: Vardeny
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Detry
authors.forename: John J M
authors.initials: JJ
authors.lastname: Moran
authors.forename: Maryl R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D003062:Codon; D005215:Fasting / Q000097:blood; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002227:Carbazoles; D003062:Codon; D007328:Insulin; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D000077261:Carvedilol; D008790:Metoprolol