Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control

Abstract

Aims/hypothesis We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control. Methods Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peakvalley respiratory sinus arrhythmia [pvRSA], and highfrequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine). Results Serum insulin level was positively associated with HR at all time points during the clamps except the firstphase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log 10 HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures. Conclusion/interpretation Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.Keywords Autonomic nervous system . GLP-1 . Heart rate variability . Insulin . Parasympathetic activityGlucagon-like peptide-1 HF High-frequency power HRV Heart-rate variability IBI Interbeat interval of the heart rate ISI Insulin sensitivity index pvRSA Peak-valley respiratory sinus arrhythmia rMSSD Root mean square of successive differences RSA Respiratory sinus arrhythmia

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