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

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% CO2. Methods: The 35% CO2 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 CO2-induced bradycardia seen in the non-neuropathic patients ( p< 0.0001). Conclusions/ interpretation: The CO2 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.