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Abstract
Objectives Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping.
Setting Secondary healthcare unit in Copenhagen, Denmark.
Participants 24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years.
Interventions In this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen.
Primary and secondary outcome measures Primary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF).
Results Systolic BP dipping increased 2.4% (0.03–4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (−0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study.
Conclusions We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined.
Trial registration number EudraCT2012-002136-90; Post-results.
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Footnotes
Contributors HØH contributed substantially to the conception and design of the study, acquisition, analysis and interpretation of data, drafted the manuscript and has approved the final version of the manuscript. TJ contributed substantially to the conception and design of the study, acquisition, analysis and interpretation of data, drafted and revised the manuscript and has approved the final version of the manuscript. UMM and PES contributed substantially to the conception and design of the study, analysis and interpretation of data, revised the manuscript and has approved the final version of the manuscript. KFK and LK contributed substantially to the conception and design of the study, interpretation of data, revised the manuscript and has approved the final version of the manuscript. KLH contributed to the design of the study, acquisition and interpretation of data, revised the manuscript and has approved the final version of the manuscript. HC contributed to the design of the study, acquisition, analysis and interpretation of data, revised the manuscript and has approved the final version of the manuscript. ST contributed to the conception and design of the study, acquisition and analysis of data, revised the manuscript and has approved the final version of the manuscript. JH contributed substantially to the conception and design of the study, analysis and interpretation of data, revised the manuscript and has approved the final version of the manuscript. HØH is the guarantor of this study; he had full access to all the data in the study and had final responsibility for the decision to submit for publication. Previous publication: Part of the data has been presented at the American Diabetes Association, 75th Annual Scientific Session 5–9th of June 2015 and at the European Association for the Study of Diabetes, 51st Annual Meeting, September 14–18 2015.
Funding This study was supported by a grant from the Arvid Nilssons Foundation and AP Moeller Foundation.
Competing interests None declared.
Ethics approval Danish Scientific Ethical Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.