Circadian-timed quick-release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus.

ABSTRACT: Objective: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. Design and 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). Results: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 [P = .02], -1.9 [P = .05], -2.5 [P = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (-2.7 [P = .03], -5 [P = .002], -6.1 [P = .002] with bHbA1c ?7, >7, ?7.5%, respectively] in the bRHR ?70 group and more so with bRHR ?80 (-4.5 [P = .07], -7.8 [P = .015], -9.9 [P = .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 (P = .04), -0.73 (P = .005) and -1.22 (P = .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. Conclusion: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.

SUBMITTER: Chamarthi B 

PROVIDER: S-EPMC6947713 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature