Severity of Autonomic and Sensory Neuropathy and the Impairment of Visual- and Auditory-Evoked Potentials in Type 1 Diabetes

Is there a relationship?

It became clear in the last decades that neuropathy is not a separate clinical entity, but a component of several related complications (1). Although the functional consequences of neuropathy are well defined in various organ systems, the relationship of the alterations in the networks of the neuronal system is still poorly documented. Assessment of the potential common alterations of the different neuronal functions in patients with diabetic neuropathy may provide new pathogenetic and diagnostic considerations. Previously, we observed correlations between the delay of certain auditory-evoked potentials and the severity of autonomic and peripheral sensory neuropathy in patients with type 1 diabetes (2). In addition, we found a relationship between the latency of visual-evoked potentials and the peripheral neuronal function (3). The aims of this study were to analyze the possible correlations between the central auditory and visual afferentations and the severity of autonomic and sensory neuropathy in patients with long-standing type 1 diabetes.

A total of 10 middle-aged type 1 diabetic patients with long-standing diabetes were included in the study (4 male and 6 female subjects aged 43.8 ± 15.2 years [mean ± SD], duration of diabetes 23.1 ± 9.3 years, BMI 27.9 ± 3.9 kg/m²). Patients with abnormal hearing, proliferative retinopathy, impaired visual acuity, or neuropathy of origin other than diabetes were excluded. The quantitative characteristics of the brainstem function were evaluated by the detection of auditory-evoked potentials after the delivery of an audible click of short duration via an earphone (4). The latencies of the first five waves (I–V) were analyzed in this study. The central afferent visual function was evaluated via the delay of the major positive component (P100) of the visual-evoked potentials that was generated following a pattern-reversal checkboard stimulation (5). Cardiovascular autonomic function was assessed by means of the five standard cardiovascular reflex tests (2,3,6). The heart rate tests (the heart rate response to deep breathing, the 30:15 ratio, and the Valsalva ratio) mainly reflect the parasympathethic function, whereas the systolic blood pressure response to standing up and the diastolic pressure change to a sustained handgrip predominantly characterize the sympathetic integrity. Detection of current perception thresholds (CPTs) with a neuroselective transcutaneous stimulator, the Neurometer (Neurotron, Baltimore, MD), allowed for the assessment of the sensory function at three different frequencies on the median and peroneal nerves (6). The analysis of the auditory-evoked potentials revealed negative relationships between the heart rate tests and the prolongation of the latencies of waves III and V (heart rate response to breathing–wave III, r = −0.586, P < 0.01; 30:15 ratio–wave III, r = −0.588, P < 0.01; heart rate response to breathing–wave V, r = −0.498, P < 0.05; Valsalva ratio–wave V, r = −0.463, P < 0.05; and 30:15 ratio–wave V, r = −0.599, P < 0.01). The statistical procedure demonstrated positive correlations between higher CPT values obtained at 2,000 and 250 Hz at the peroneal nerve and the latencies of wave V (CPT at 2,000 Hz–wave V, r = 0.527, P < 0.01; and CPT at 250 Hz–wave V, r = 0.547, P < 0.01). The delayed visual afferent function correlated negatively with the heart rate tests, similar to the finding of the auditory-evoked potentials (heart rate response to breathing–P100, r = −0.51, P < 0.05; Valsalva ratio–P100, r = −0.552, P < 0.01; and 30:15 ratio–P100, r = −0.438, P < 0.05). Positive associations were proven between the degree of the peripheral sensory dysfunction on the peroneal nerve and the latency of the P100 potentials (CPT at 2,000 Hz–P100, r = 0.461, P < 0.05; CPT at 250 Hz–P100, r = 0.521, P < 0.05; and CPT at 5 Hz–P100, r = 0.561, P < 0.01). The final evaluation of the results demonstrated a correlation between the latencies of the auditory- and visual-evoked potentials in this group of patients (wave V–P100, r = 0.571, P < 0.01).

In this study, the severity of the parasympathetic impairment and the lower-limb sensory neuropathy was consequently associated with the latencies of both the auditory- and the visual-evoked potentials. These findings validate our previous data that central afferent dysfunction is associated with the most common forms of diabetic neuropathy. Moreover, as a novel observation, a correlation was found between the impairment of the auditory- and visual-evoked potentials, suggesting that different central manifestations are related to each other. The regions responsible for the generation of the waves III and V of the auditory-evoked potentials and the P100 potentials in the central nervous system may be similarly sensitive to the pathogenetic process, resulting in neuropathy in the peripheral nerves. Our findings also suggest that the abnormal central afferentation might play an important role in the development of the parasympathetic efferent dysfunctions. The assessment of these characteristic alterations of the central conduction may provide an additional diagnostic approach for a more precise detection of the central manifestations of diabetic neuropathy.