Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping: a randomised, placebo-controlled, double-blind cross-over trial

Abstract

ObjectivesCardiovascular 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.SettingSecondary healthcare unit in Copenhagen, Denmark.Participants24 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.InterventionsIn 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 measuresPrimary 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).ResultsSystolic 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.ConclusionsWe 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 numberEudraCT2012-002136-90; Post-results.

Cardiac ventricular sizes are reduced in patients with long-term, normoalbuminuric type 1 diabetes compared to the non-diabetic background population

“…This was a cross-sectional study that included normoalbuminuric, long-term type 1 diabetes persons examined with cardiac MDCT scans as part of previous studies. 18,19 For comparison to the background population, participants without diabetes but of similar age and sex without known CV disease enrolled in the Copenhagen General Population Study (CGPS) were identified.…”

“…Questions regarding medical history and collection of blood samples were acquired as previously reported. 16,18,19 Weight, height and blood pressure (BP) were also recorded. Body surface area (BSA) was calculated according to Du Bois' formula (BSA = 0.007184 × height (cm) 0.725 × weight (kg) 0.425 ) and used for indexed values of the cardiac chamber measures.…”

Chronotherapy for Hypertension

“…At present, there is only one published study investigating morning compared to evening dosing of antihypertensive medications in individuals with type 1 diabetes. This report suggests that bedtime dosing of an ACEI in patients with CV autonomic neuropathy increased nighttime BP dipping (188). A cross-sectional study in participants with type 2 diabetes reported bedtime medication administration was a positive predictor for a normal dipping BP pattern and that CCBs and β-blockers were more likely to be administered at bedtime than in the morning (189).…”

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review

“…Hypertension, renal function impairment and altered nocturnal sympathovagal balance are often linked to the aetiology of non-dipping 61,62 and non-dipping is sometimes considered as a surrogate measure of CAN [63][64][65][66] .…”