The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker.
The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker.
复制标题
β2 肾上腺素受体 Gln27Glu 多态性影响心力衰竭患者的胰岛素抵抗：通过选择 β 受体阻滞剂可能进行调节。
DOI：
10.1097/fjc.0b013e31818f5739
复制
发表时间：
2008
影响因子：
3
通讯作者：
Sweitzer,NancyK
中科院分区：
文献类型：
--
作者：
Vardeny,Orly;Detry,MichelleA;Moran,JohnJM;Johnson,MarylR;Sweitzer,NancyK
胰岛素抵抗在心力衰竭（HF）患者中普遍存在，β 2肾上腺素能受体（β 2-AR）参与葡萄糖稳态。我们假设β 2-AR Gln 27 Glu和Arg 16 Gly多态性影响HF患者的胰岛素抵抗，并探讨β 2-AR多态性对葡萄糖处理的影响是否可通过选择β受体阻滞剂来改变。我们研究了30例有心脏收缩功能障碍病史的非糖尿病心力衰竭成人患者，其中15例接受琥珀酸美托洛尔治疗，15例接受卡维地洛治疗。我们测量了空腹血糖、胰岛素和胰岛素抵抗，并确定了密码子27和16处的β 2-AR基因型。该队列为胰岛素抵抗，平均HOMA-IR评分为3.4（95% CI，2.3 - 4.5;正常值，1.0）。与携带Gln等位基因的个体相比，具有Glu 27 Glu基因型的患者表现出更高的胰岛素和HOMA-IR（P= 0.019）。服用卡维地洛的患者如果在密码子27处也携带野生型等位基因，则胰岛素抵抗较低（空腹胰岛素，9.8±10.5 vs 20.5±2.1，P= 0.072; HOMA-IR，2.4±2.7 vs 5.1±0.6，P= 0.074）;服用琥珀酸美托洛尔的患者无论基因型如何，胰岛素抵抗均较高。β 2-AR Glu 27 Glu基因型可能与HF患者胰岛素浓度升高和胰岛素抵抗相关。未来的研究需要证实卡维地洛治疗是否与β 2-AR密码子27 Gln携带者的胰岛素和胰岛素抵抗降低有关。
Insulin resistance is prevalent in heart failure (HF) patients, and beta 2 adrenergic receptors (β 2-AR) are involved in glucose homeostasis. We hypothesized that β 2-AR Gln27Glu and Arg16Gly polymorphisms affect insulin resistance in HF patients, and we explored if effects of β 2-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 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.