Physiological and Clinical Correlates of Cardiorespiratory Reflexes in Diabetes Mellitus

Abstract

Cardiorespiratory reflexes (CRRs) were studied by measuring heart-rate (HR) variation during 6 breaths/min respiration (delta R6) and Valsalva maneuver (VR) in 145 healthy and 417 type I (insulin-dependent) diabetic subjects. HR variation with breathing at 12 breaths/min and ventilatory response to hypercapnia/hypoxia were measured in fewer subjects. CRR results were compared with symptoms of autonomic dysfunction, the neurological examination, nerve conduction studies, and quantitative sweat testing. The objective was to compare the sensitivity of various methods of characterizing diabetic patients and to use this information when staging patients for clinical therapeutic trials. CRR responses were age dependent in both populations. Either delta R6 or VR was abnormal in 74% of diabetic patients, delta R6 being more sensitive. CRRs correlated well with the presence of symptoms of autonomic dysfunction, abnormalities on the neurological examination, results of nerve conduction studies, and sweating activity in the feet of the same patients. However, both CRRs and sweating were abnormal in a high proportion of patients without any clinical manifestations of neuropathy. The ventilatory reflex response to moderate hypercapnia/hypoxia was also measured. It was normal in most of the diabetic patients tested, including many with severe reduction of CRRs. We conclude from the combined results of CRR, ventilatory response, and other studies that the causative factors for abnormal CRR may not be confined to the vagus nerves, and that in most instances, the depressed CRR may be due to a decrease in the efficacy of sensorimotor nerve conduction around the reflex arc.

Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus

“…In view of these results, it is clear that in order to establish whether HRR to deep breathing is abnormal it is necessary to consider the age of the subject tested. These results are similar to those reported by Kennedy et al (10).…”

“…Since the procedure of calculating the responses using the recordings of the electrocardiograph obtained during the maneuvers are tedious and, in order to decrease the variability, they must always be carried out by the same person, they cannot be used for trials conducted for long periods of time and for evaluating many individuals. Some studies define normal responses in populations of subjects without diabetes mellitus (DM) as the minimal value observed (9) whereas others use the 95th or 96th percentile (10,11), the mean/standard deviation (12) or they do not state how normality was established (13,14). These observations and also the recommendations of reseachers in this area (15,16) that standardization of the methods is the first objective in studying cardiovascular autonomic complications of diabetes motivated us to perform the present study.…”

Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation

“…Cardiorespiratory reflex (CRR) tests can detect abnormal cardiovascular function in as many as 75% of diabetic subjects (Hilsted and Jensen 1979;Dyberg et al 1981;Ewing et al 1985;Low et al 1986;Zola et al 1986;Kennedy et al 1989), often at the time diabetes is first diagnosed (Canal et al 1978;Pfeifer et al 1984), even though 27% or fewer have symptoms of autonomic dysfunction Canal et al 1978;Young et al 1983). Moreover, abnormalities on CRR testing are generally considered to be associated with an increased frequency of sudden death (Page and Watkins 1978) and an increased mortality rate (Ewing et al 1976;.…”

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients

“…The relevance of these findings in the clinical evaluation of this disease has not been well established (8,9). Furthermore, it is well known that diabetes mellitus may damage the autonomic nervous system of virtually all organs, with clinical manifestations of dysautonomy being more common in the cardiovascular, genitourinary, gastrointestinal, and thermoregulatory systems (10). In the non-insulin dependent, type 2, diabetic population, there is evidence that the expression of neural damage may be more complex due to overlapping hormonal, metabolic, and circulatory effects associated with old age (11).…”