Autonomic imbalance: prophet of doom or scope for hope?

Abstract

It has long been recognized that cardiac autonomic neuropathy increases morbidity and mortality in diabetes and may have greater predictive power than traditional risk factors for cardiovascular events. Significant morbidity and mortality can now be attributable to autonomic imbalance between the sympathetic and parasympathetic nervous system regulation of cardiovascular function. New and emerging syndromes include orthostatic tachycardia, orthostatic bradycardia and an inability to use heart rate as a guide to exercise intensity because of the resting tachycardia. Recent studies have shown that autonomic imbalance may be a predictor of risk of sudden death with intensification of glycaemic control. This review examines an association of autonomic dysregulation and the role of inflammatory cytokines and adipocytokines that promote cardiovascular risk. In addition, conditions of autonomic imbalance associated with cardiovascular risk are discussed. Potential treatment for restoration of autonomic balance is outlined.

FIGURE 1

Parasympathetic and sympathetic measurement model. FRF, fundamental respiratory frequency; HR, heart rate; Lfa, low frequency area; Lfa/Rfa, sympathovagal balance; mHR, mean heart rate; RA, respiratory activity; Rfa, respiration frequency area; RSA, respiratory sinus arrhythmia.

FIGURE 2

The ability to correct sympathetic excess with a β-adrenergic blocking agent. Δ, sympathetic withdrawal with an adrenergic agonist and parasympathetic excess with an anti-cholinergic agent [80]. BP, blood pressure; HR, heart rate; PE, parasympathetic excess; SE, sympathetic excess; SW, sympathetic withdrawal.

FIGURE 3

Suggestions of pharmaceutical approaches to the treatment or prevention of autonomic dysfunction in diabetes. Central to this evolving concept is the role of adipocytokines and inflammation. AGE, advanced glycation end product; ARB, angiotensin receptor blocker; ARI, aldose reductase inhibitor; e-NOS, endothelial nitric oxide synthase; IL-6 interleukin 6; i-NOS, inducible nitric oxide synthase; NFkB, nuclear factor-kappa B; PKC, protein kinase C; PPAR, peroxisome proliferator activated receptor; ROS, reactive oxygen species; SOD, superoxide dimutase; TNF-α, tumour necrosis factor alpha; Adapted from Vinik et al. (2006) with permission from the authors and the publishers of Vascular Pharmacology [46].