, Volume 59, Issue 2, pp 390–391 | Cite as

Antihypertensive medication prior to nocturnal sleep reduces the risk of new-onset type 2 diabetes in hypertensive patients: a role for slow-wave sleep?

  • Christian BenedictEmail author


Antihypertensive medication Chronotherapy Sleep Type 2 diabetes 



Sympathetic nervous system


Slow-wave sleep

To the Editor: I read with great interest the study by Hermida et al [1]. In their study involving 2,012 hypertensive patients without type 2 diabetes, it was found that regular bedtime vs morning intake of antihypertensive medication reduced the risk of new-onset type 2 diabetes, with the strongest risk reduction associated with the use of ACE inhibitors. Moreover, compared with the morning-treatment group, patients on the bedtime medication schedule exhibited a larger relative blood pressure decline across sleep. These findings provide novel evidence as they suggest that circadian timing of antihypertensive medication can alter patients’ type 2 diabetes risk. The question is: why do ACE inhibitors have such a protective effect against diabetes when intake is scheduled prior to nocturnal sleep?

Following enzymatic conversion of angiotensin 1 into angiotensin 2 (inhibited by ACE inhibitors), the latter exerts complex cardiovascular actions, including sympathoexcitation [2]. Studies have shown that increased activity of the sympathetic nervous system (SNS) can alter human sleep. For example, in response to peripheral infusions of the α-adrenergic agonist phenylephrine which does not pass the blood–brain barrier, during first hours of nocturnal sleep, healthy normotensive volunteers are more prone to intermittent wakefulness and spend less time in slow-wave sleep (SWS) [3]. Experimental reductions of SWS and interruptions of sleep have recently been linked to impaired morning insulin sensitivity in healthy humans [4, 5]. With these results in mind, it could be speculated that intake of ACE inhibitors close to sleep onset dampens nocturnal activity of the SNS, and thereby reduces frequency of awakenings after sleep onset and increases time in SWS (Fig. 1). Such promotion of sleep consolidation could therefore offer an alternative mechanism through which bedtime ingestion of ACE inhibitors reduces the risk of new-onset type 2 diabetes in hypertensive patients [1]. Importantly, there are also other sympatholytic antihypertensive drugs that have been shown to affect human sleep, e.g. the centrally acting α2-adrenergic receptor agonist clonidine [6]. It could therefore be hypothesised that sympatholytic antihypertensive drugs other than ACE inhibitors, if regularly ingested near to bedtime, may also reduce the type 2 diabetes risk in hypertensive patients. Finally, there are also other functions that benefit from SWS, e.g. formation of long-term memories [7] and initiation of adaptive immune responses [8]. Thus, scheduling the intake of sympatholytic antihypertensive drugs near to intended bedtime may offer additional health benefits for hypertensive patients.
Fig. 1

Proposed scheme through which regular intake of sympatholytic antihypertensive drugs (e.g. ACE inhibitors) prior to nocturnal sleep reduces risk of new-onset type 2 diabetes in hypertensive patients



The author’s work is supported by research grants from the Swedish Brain Foundation, AFA Insurance (Sweden), and Novo Nordisk Foundation (Denmark).

Duality of interest

The author is unaware of any affiliation, funding or financial holdings that might be perceived as affecting the objectivity of this commentary. The author declares that there is no duality of interest associated with this manuscript.

Contribution statement

The author was the sole contributor to this paper.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of NeuroscienceUppsala UniversityUppsalaSweden

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