Diabetologia

, Volume 59, Issue 2, pp 255–265

Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial

Authors

    • Bioengineering and Chronobiology Laboratories, E.I. TelecomunicaciónUniversity of Vigo
  • Diana E. Ayala
    • Bioengineering and Chronobiology Laboratories, E.I. TelecomunicaciónUniversity of Vigo
  • Artemio Mojón
    • Bioengineering and Chronobiology Laboratories, E.I. TelecomunicaciónUniversity of Vigo
  • José R. Fernández
    • Bioengineering and Chronobiology Laboratories, E.I. TelecomunicaciónUniversity of Vigo
Article

DOI: 10.1007/s00125-015-3749-7

Cite this article as:
Hermida, R.C., Ayala, D.E., Mojón, A. et al. Diabetologia (2016) 59: 255. doi:10.1007/s00125-015-3749-7

Abstract

Aims/hypothesis

We investigated whether therapy with the entire daily dose of ≥1 hypertension medications at bedtime exerts greater reduction in the risk of new-onset diabetes than therapy with all medications upon awakening.

Methods

We conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without diabetes, 976 men and 1,036 women, 52.7 ± 13.6 years of age. Patients were randomised, using a computer-generated allocation table, to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime. Investigators blinded to the hypertension treatment scheme of the patients assessed the development of new-onset diabetes.

Results

During a 5.9-year median follow-up, 171 participants developed type 2 diabetes. Patients of the bedtime, compared with the morning-treatment group, showed: (1) significantly lower asleep BP mean, greater sleep-time relative BP decline and attenuated prevalence of non-dipping at the final evaluation (32% vs 52%, p < 0.001); and (2) significantly lower HR of new-onset diabetes after adjustment for the significant influential characteristics of fasting glucose, waist circumference, asleep systolic BP mean, dipping classification and chronic kidney disease (CKD) (unadjusted HR 0.41 [95% CI 0.29, 0.58]; adjusted HR 0.43 [0.31, 0.61]; event-rate 4.8% vs 12.1% with bedtime and morning treatment, respectively; p < 0.001). Greater benefit was observed for bedtime compared with awakening treatment with angiotensin receptor blockers (ARBs) (HR 0.39 [0.22, 0.69]; p < 0.001), ACE inhibitors (0.31 [0.12, 0.79], p = 0.015) and β-blockers (0.35 [0.14, 0.85], p = 0.021).

Conclusions/interpretation

In hypertensive patients without diabetes, ingestion of ≥1 BP-lowering medications at bedtime, mainly those modulating or blocking the effects of angiotensin II, compared with ingestion of all such medications upon awakening, results in improved ambulatory BP (ABP) control (significant further decrease of asleep BP) and reduced risk of new-onset diabetes.

Trial registration: ClinicalTrials.gov NCT00295542

Funding: This independent investigator-promoted research was supported by unrestricted grants from Ministerio de Ciencia e Innovación (SAF2006-6254-FEDER; SAF2009-7028-FEDER); Xunta de Galicia (PGIDIT03-PXIB-32201PR; INCITE07-PXI-322003ES; INCITE08-E1R-322063ES; INCITE09-E2R-322099ES; 09CSA018322PR); and Vicerrectorado de Investigación, University of Vigo.

Keywords

Ambulatory blood pressure monitoringBedtime therapyRenin–angiotensin blockadeSleep-time blood pressureType 2 diabetes

Abbreviations

ABP

Ambulatory BP

ABPM

Ambulatory BP monitoring

ACEI

ACE inhibitor

ARB

Angiotensin receptor blocker

CCB

Calcium channel blocker

CKD

Chronic kidney disease

CKD-EPI

CKD Epidemiology Collaboration

CVD

Cardiovascular disease

DBP

Diastolic BP

DREAM

Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication

HOPE

Heart Outcomes Prevention Evaluation

MAPEC

Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares

PP

Pulse pressure

PROBE

Prospective, randomised, open-label, blinded endpoint

RAAS

Renin–angiotensin–aldosterone system

SBP

Systolic BP

Copyright information

© Springer-Verlag Berlin Heidelberg 2015