Project: Research project

Project Details


The recognition of alterations in cardiac autonomic function in
asymptomatic Type I insulin-dependent diabetic (IDDM) individuals has been
facilitated by the development of standardized cardiovascular reflex tests
from which inferences about autonomic integrity are drawn. Recent
experimental and clinical evidence points to the existence of a left
ventricular structural and functional impairment associated with diabetes
mellitus that raises the possibility that early in IDDM disease
progression the cardiovascular dysfunction detected by standard diagnostic
tests may be due to cardiac pathology rather than autonomic neuropathy.
This revision of a proposed 4-year study will extend our previous NHLBI-
funded work in evaluating autonomic mediation of dynamic cardiovascular
function and noninvasive diagnostic approaches for assessing diabetic
neuropathy. We will study healthy and IDDM (of more than 10 years
duration) men and women (n=130 of 144 recruited), 18-55 years old. IDDM
subjects with abnormal and normal autonomic function will be classified
using a standard battery of autonomic integrity tests. Group assignment
using the standard classification method will be compared with an
alternative autonomic classification method that is based on a
quantitative clustering technique. Echocardiographic evaluation of left
ventricular structure and function will be performed. Then autonomic
contribution to the cardiovascular response to orthostatic challenge will
be noninvasively assessed using: l) selective pharmacologic blockade; 2)
V-hat, a quantitative index of parasympathetic cardiac neural input; 3)
systolic time interval estimates of sympathetic myocardial input; and 4)
measures of hemodynamic function (heart rate, blood pressure, cardiac
output, peripheral resistance). Subjects will be tested under four
conditions: placebo, 13-sympathetic blockade, parasympathetic blockade,
and combined 13-sympathetic and parasympathetic blockade. The
comprehensive assessment of hemodynamic function during rest and postural
adjustment (head-up and head-down tilt) in each of the pharmacologic
blockade conditions will provide information about the autonomic
contribution to hemodynamic regulation in IDDM individuals. The degree of
autonomic blockade will be assessed pharmacologically. These data
together with the information derived from the echocardiographic left
ventricular assessment will yield information regarding IDDM disease
progression in relation to the sensitivity and specificity of the standard
and alternative IDDM classification methods.
Effective start/end date8/1/957/31/00


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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