title: A new test for autonomic cardiovascular and neuroendocrine responses in diabetes mellitus: evidence for early vagal dysfunction.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. joey.kaye@health.wa.gov.au
authors.forename: J M
authors.initials: JM
authors.lastname: Kaye
authors.forename: R J
authors.initials: RJ
authors.lastname: Corrall
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure; D002319:Cardiovascular System / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology*