Autonomic nervous system testing is used to document diabetic autonomic failure. Diabetic autonomic failure is defined as impaired function of the peripheral autonomic nervous system and can be divided into two categories: 1) autonomic neuropathy, in which there is a structural lesion of the peripheral autonomic neuron and 2) functional autonomic failure, in which no known structural lesion occurs. In addition to the classic neurotransmitters (acetylcholine and norepinephrine), newer neurotransmitters and neuromodulators such as substance P, neuropeptide K, calcitonin gene-related peptide, and nitric oxide are also involved. Also, the adrenal medullae are an integral part of the autonomic nervous system. With these caveats, the following definition is proposed, wherein autonomic abnormalities are classified as structural or functional with further subdivisions based on the overt or subclinical nature of the disorder, the specific subdivisions of the autonomic nervous system, and the specific organ systems involved.
In the setting of diabetes mellitus without other causes of autonomic neuropathy there is a structural lesion that comprises a diffuse disorder of small nerve fibers of the cholinergic, adrenergic, and peptidergic nervous systems. This may be further divided into: 1) subclinical—that which is diagnosed only by tests and 2) clinical—that which presents with symptoms or signs.
Reduced autonomic responses not attributable to classic diabetic autonomic neuropathy also occur and cause clinically important problems. An example is hypoglycemia associated autonomic failure. HAAF is a recently described functional disorder without a known structural lesion characterized by selectively reduced adrenomedullary (epinephrine) and parasympathetic (pancreatic polypeptide) responses to a given degree of hypoglycemia. It is associated with the interrelated clinical syndromes of defective glucose counter regulation, hypoglycemia unawareness, and elevated glycemic thresholds for symptoms of and autonomic responses to hypoglycemia during effective intensive therapy, and with a high frequency of iatrogenic hypoglycemia. A further example of functional autonomic failure is the impairment of gastric emptying with severe hyperglycemia.
The autonomic nervous system is usually tested by evaluating reflex arcs. A reflex arc involves a stimulus, a receptor, an afferent nerve, central processing, an efferent nerve and an endorgan response. In addition to the reflex arc, there are several synapses involved throughout the pathway and different neurotransmitters at each synaptic cleft. It is important that, where possible, the confounding variables, standardization of stimulus, and normal end-organ function be established before one elicits the reflex arc to test the autonomic nervous system. Many organs are dually innervated. Innervation of parasympathetic and sympathetic pathways often work as a check and balance system. Therefore, where possible, the autonomic nervous system needs to be evaluated recognizing that the result may reflect a decrease in one pathway or an increase in another. An ideal test should be simple, noninvasive, and easy for the operator and subjects, reproducible, sensitive, relevant to known physiological functions, suitable for longitudinal evaluation, and specific. The confounding variables affecting the test should be fairly well delineated. Some of the current autonomic tests fulfill nearly all of these obligations.