Chamarthi Bindu, Vinik Aaron, Ezrokhi Michael, Cincotta Anthony H
VeroScience LLC Tiverton Rhode Island.
Eastern Virginia Medical School Strelitz Diabetes Center Norfolk Virginia.
Endocrinol Diabetes Metab. 2019 Nov 13;3(1):e00101. doi: 10.1002/edm2.101. eCollection 2020 Jan.
Sympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine-QR, a dopamine-agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine-QR's effects on RHR and HbA1c in type 2 diabetes subjects.
RHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine-QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR).
In subjects with bRHR ≥70 beats/min, bromocriptine-QR vs placebo reduced RHR by -3.4 beats/min and reduced BP (baseline 130/79; systolic, diastolic, mean arterial BP reductions [mm Hg]: -3.6 [ = .02], -1.9 [ = .05], -2.5 [ = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (-2.7 [ = .03], -5 [ = .002], -6.1 [ = .002] with bHbA1c ≤7, >7, ≥7.5%, respectively] in the bRHR ≥70 group and more so with bRHR ≥80 (-4.5 [ = .07], -7.8 [ = .015], -9.9 [ = .005]). Subjects with bRHR <70 had no significant change in RHR or BP. With bHbA1c ≥7.5%, %HbA1c reductions with bromocriptine-QR vs placebo were -0.50 ( = .04), -0.73 ( = .005) and -1.22 ( = .008) with bRHR <70, ≥70 and ≥80, respectively. With bRHR ≥70, the magnitude of bromocriptine-QR-induced RHR reduction was an independent predictor of bromocriptine-QR's HbA1c lowering effect.
Bromocriptine-QR lowers elevated RHR with concurrent decrease in BP and hyperglycaemia. These findings suggest a potential sympatholytic mechanism contributing to bromocriptine-QR's antidiabetes effect and potentially its previously demonstrated effect to reduce CVD events.
交感神经系统（SNS）过度活跃是胰岛素抵抗和心血管疾病（CVD）的一个风险因素。我们评估了溴隐亭-QR（一种多巴胺激动剂抗糖尿病药物）对静息心率（RHR）升高（代谢综合征中SNS过度活跃的一个标志物）、血压（BP）的影响，以及溴隐亭-QR对2型糖尿病患者RHR和糖化血红蛋白（HbA1c）影响之间的关系。
在一项随机对照试验的数据的事后分析中，评估了1014例2型糖尿病患者的RHR和BP变化。这些患者被随机分为接受溴隐亭-QR或安慰剂加标准治疗（饮食±≤2种口服抗糖尿病药物），为期24周，期间不改变抗高血压或抗糖尿病药物，按基线RHR（bRHR）分层。
在bRHR≥70次/分钟的患者中，与安慰剂相比，溴隐亭-QR使RHR降低了-3.4次/分钟，并降低了血压（基线为130/79；收缩压、舒张压、平均动脉压降低值[mmHg]：-3.6[P=0.02]，-1.9[P=0.05]，-2.5[P=0.02]）。RHR降低幅度随基线HbA1c（bHbA1c）升高而增加（在bRHR≥70组中，bHbA1c≤7%、>7%、≥7.5%时分别为-2.7[P=0.03]，-5[P=0.002]，-6.1[P=0.002]；bRHR≥80时更明显，分别为-4.5[P=0.07]，-7.8[P=0.015]，-9.9[P=0.005]）。bRHR<70的患者RHR和BP无显著变化。当bHbA1c≥7.5%时，与安慰剂相比，溴隐亭-QR使HbA1c降低的百分比在bRHR<70、≥70和≥80时分别为-0.50（P=0.04），-0.73（P=0.005）和-1.22（P=0.008）。在bRHR≥70时，溴隐亭-QR引起的RHR降低幅度是溴隐亭-QR降低HbA1c效果的一个独立预测因素。
溴隐亭-QR可降低升高的RHR，同时降低血压和高血糖。这些发现提示了一种潜在的交感神经抑制机制，有助于溴隐亭-QR的抗糖尿病作用，以及其先前已证明的降低CVD事件的作用。
