Vardeny Orly, Detry Michelle A, Moran John J M, Johnson Maryl R, Sweitzer Nancy K
University of Wisconsin School of Pharmacy, Pharmacy Practice Division, Madison, WI 53705-2222, USA.
J Cardiovasc Pharmacol. 2008 Dec;52(6):500-6. doi: 10.1097/FJC.0b013e31818f5739.
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.
胰岛素抵抗在心力衰竭（HF）患者中普遍存在，并且β2肾上腺素能受体（β2-AR）参与葡萄糖稳态。我们假设β2-AR Gln27Glu和Arg16Gly多态性会影响HF患者的胰岛素抵抗，并且我们探讨了β受体阻滞剂的选择是否会改变β2-AR多态性对葡萄糖代谢的影响。我们研究了30名患有HF且有收缩功能障碍病史的非糖尿病成年人；15人接受琥珀酸美托洛尔治疗，15人接受卡维地洛治疗。我们测量了空腹血糖、胰岛素和胰岛素抵抗，并确定了第27和16密码子处的β2-AR基因型。该队列存在胰岛素抵抗，平均稳态模型评估胰岛素抵抗（HOMA-IR）评分为3.4（95%可信区间，2.3至4.5；正常值，1.0）。与携带Gln等位基因的个体相比，Glu27Glu基因型的患者表现出更高的胰岛素水平和HOMA-IR（P = 0.019）。服用卡维地洛的患者如果在第27密码子处也携带野生型等位基因，则表现出较低的胰岛素抵抗（空腹胰岛素，变异型为9.8±10.5，野生型为20.5±2.1，P = 0.072；HOMA-IR，变异型为2.4±2.7，野生型为5.1±0.6，P = 0.074）；接受琥珀酸美托洛尔治疗的患者无论基因型如何都有高胰岛素抵抗。β2-AR Glu27Glu基因型可能与HF患者较高的胰岛素浓度和胰岛素抵抗有关。需要进一步的研究来证实卡维地洛治疗是否可能与β2-AR第27密码子Gln携带者的胰岛素和胰岛素抵抗降低有关。
