Insulin- and glucagon-like peptide-1-induced changes in heart rate and vagosympathetic activity: why they matter

Heart rate (HR) predicts cardiovascular morbidity and mortality in individuals either with or without diabetes. In type 2 diabetic patients, cardiac autonomic neuropathy is a risk marker for cardiac morbidity and mortality. A major pathogenic potential may be attributed to vagal depression and sympathetic predominance. In this issue of Diabetologia, Berkelaar et al (DOI: 10.​1007/​s00125-013-2848-6) examined the effects of euglycaemic, and hyperglycaemic clamp with the addition of glucagon-like-peptide-1 (GLP-1) and arginine, on cardiac vagal control in a large number of healthy subjects. After adjustments for age, BMI and insulin sensitivity, insulin associations with HR remained partially intact while those with vagal control disappeared. This suggested that BMI and insulin sensitivity, but not insulin levels, were the main drivers of cardiac vagal control. GLP-1 infusion during hyperglycaemia increased HR and BP and produced a statistically non-significant decrease in measures of cardiac vagal control compared with values before any manipulation of insulin levels. This commentary summarises how, and to what extent, insulin and GLP-1 affect autonomic nervous system activity, HR and BP. More information is needed on the mechanisms through which acute administration of, and long-term treatment with, GLP-1 may affect haemodynamics and autonomic activity in diabetic and obese patients, since this may influence cardiovascular outcomes.