Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel‐group study

Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide...

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Published inEndocrinology, diabetes & metabolism Vol. 2; no. 2; pp. e00058 - n/a
Main Authors Nyström, Thomas, Santos‐Pardo, Irene, Fang, Xin, Cao, Yang, Hedberg, Fredric, Jendle, Johan
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.04.2019
John Wiley and Sons Inc
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Online AccessGet full text
ISSN2398-9238
2398-9238
DOI10.1002/edm2.58

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Abstract Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. Methods This was a post hoc study whereas sixty‐two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat‐to‐beat (NN) intervals (SDNN), was assessed by 24‐hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high‐frequency (HF), low‐frequency (LF) and very low‐frequency power. Results Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide‐treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Conclusions Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in type 2 diabetes patients on the cardiovascular risk parameters heart rate (HR) and heart rate variability (HRV). Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathovagal balance.
AbstractList Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. Methods This was a post hoc study whereas sixty‐two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat‐to‐beat (NN) intervals (SDNN), was assessed by 24‐hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high‐frequency (HF), low‐frequency (LF) and very low‐frequency power. Results Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide‐treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Conclusions Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in type 2 diabetes patients on the cardiovascular risk parameters heart rate (HR) and heart rate variability (HRV). Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathovagal balance.
AimsReduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV.MethodsThis was a post hoc study whereas sixty‐two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat‐to‐beat (NN) intervals (SDNN), was assessed by 24‐hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high‐frequency (HF), low‐frequency (LF) and very low‐frequency power.ResultsBaseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide‐treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis.ConclusionsLiraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.
Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV.AIMSReduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV.This was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power.METHODSThis was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power.Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis.RESULTSBaseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis.Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.CONCLUSIONSLiraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.
Aims: Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. Methods: This was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power. Results: Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P  = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Conclusions: Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.
Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. This was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power. Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute,  = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.
Author Fang, Xin
Nyström, Thomas
Cao, Yang
Jendle, Johan
Hedberg, Fredric
Santos‐Pardo, Irene
AuthorAffiliation 3 Clinical Epidemiology and Biostatistics, School of Medical Sciences Örebro University Örebro Sweden
1 Department of Clinical Science and Education Södersjukhuset Karolinska Institutet Stockholm Sweden
2 Unit of Biostatistics, Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
4 Institution of Medical Sciences Örebro University Örebro Sweden
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– name: 4 Institution of Medical Sciences Örebro University Örebro Sweden
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– name: 1 Department of Clinical Science and Education Södersjukhuset Karolinska Institutet Stockholm Sweden
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Issue 2
Keywords liraglutide
type 2 diabetes mellitus
heart rate variability
automatic nervous system
cardiac autonomic neuropathy
glimepiride
Language English
License Attribution-NonCommercial
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Notes Funding information
Financial support was provided through the Swedish Heart and Lung foundation, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet. This was an investigator‐initiated and investigator‐designed clinical trial. The investigators received unrestricted grant from Novo Nordisk A/S, but the company was not involved in data collection, study management, analysis or interpretation of data. Nor was the company involved in the decisions regarding the submission of the manuscript.
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Clinical Trial Registration: http://www.clinicaltrials.gov Unique identifier: NCT01425580.
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Snippet Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect...
Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in...
AimsReduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action...
Aims: Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and...
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StartPage e00058
SubjectTerms Antidiabetics
automatic nervous system
cardiac autonomic neuropathy
Diabetes
Generalized linear models
glimepiride
Heart attacks
Heart failure
Heart rate
heart rate variability
Hemoglobin
Hypertension
Hypoglycemia
liraglutide
Nervous system
Original
Spectrum analysis
Standard deviation
type 2 diabetes mellitus
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Title Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel‐group study
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fedm2.58
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Volume 2
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