A new test for autonomic cardiovascular and neuroendocrine responses in diabetes mellitus: evidence for early vagal dysfunction

Abstract

Aims/hypothesis: Diabetic autonomic neuropathy affects many physiological systems, producing a variety of important clinical manifestations. It is associated with high morbidity and mortality, particularly during times of stress. This is thought to be due to an increased risk of cardiac arrhythmias, although the exact mechanisms involved have yet to be fully elucidated. The aim of the present study was to investigate the endocrine, cardiac autonomic and psychological responses of diabetic patients with and without autonomic neuropathy to a single breath of 35% CO 2 . Methods: The 35% CO 2 challenge was performed in 20 male diabetic subjects, 11 of whom had autonomic neuropathy. Results: Baseline and stimulated cortisol, prolactin, systolic blood pressure and emotional arousal were similar in the two groups. However, subjects with autonomic neuropathy failed to demonstrate the expected CO 2 -induced bradycardia seen in the non-neuropathic patients (p<0.0001). Conclusions/ interpretation: The CO 2 challenge can be safely and easily administered to produce hypothalamic-pituitary-adrenal axis and cardiac autonomic activation, as well as emotional arousal. The test clearly distinguishes between subjects with and without cardiac autonomic neuropathy and could be an important adjunct to the methods currently available for the investigation and diagnosis of diabetic autonomic neuropathy.

Neuroendocrine and behavioural responses to CO2 inhalation in central versus peripheral autonomic failure

“…Previous studies involving 35% CO 2 have not, however, identified an effect of age [15,16]. In this study, the cardiovascular response to a single breath of 35% CO 2 was significantly delayed and blunted in both central (MSA) and peripheral (PAF) autonomic failure syndromes.…”

“…Prolactin is often released under conditions of stress and there is emerging evidence for its role in modifying anxiety expression [14]. Studies of prolactin responses to CO 2 are limited and conflicting with some indicating prolactin release [15], and others showing no change [16]. An expected increase in prolactin in control subjects in this study was not observed.…”

“…The HPA response appears dependent on activation of central autonomic and/or limbic centres [3,15]. The cortisol response to 35% CO 2 exposure was preserved in PAF subjects as it is in other forms of peripheral autonomic failure (diabetic autonomic neuropathy [16]). MSA subjects on the other hand showed a trend towards lower cortisol responses compared with controls reinforcing the importance of central autonomic integration for the production of CO 2 -induced responses.…”

Carbon Dioxide-Induced Emotion and Respiratory Symptoms in Healthy Volunteers

“…Moreover, dizziness might also be secondary to a transient cerebral hypoperfusion, secondary to bradycardia. Unfortunately we do not have any physiological measurement in the present study however, according to the studies of Argyropoulos et al (2002) and Kaye et al (2005) on the effects of CO 2 in healthy volunteers, the expected cardiovascular reaction to CO 2 consists in a bradycardic response accompanied by an activation of the sympathetic system with an increase in blood pressure. The bradycardia appears to be regulated independently of the pressor response and most likely involves the direct activation of brainstem vagal nuclei by CO 2 .…”

Physiological and anatomical bases for sex differences in pain and nausea as presenting symptoms of acute coronary syndromes

“…In diabetes mellitus, autonomic neuropathy is common, and tends to affect the vagal nerves before it affects the sympathetic nerves. 55 The amplitude of heartbeat-evoked brain potential is smaller in patients with diabetic neuropathy than in healthy control subjects. 56 The smaller amplitude implies a lesser perception of the stimulus, and may contribute to the diminished perception of symptoms in patients with diabetic neuropathy.…”