Diabetes may alter both the peripheral and the central nerve function, but the peripheral manifestations of diabetic neuropathy are more frequently discussed in the literature than the impairment of the central nervous system. Delay of the evoked potentials in the central pathways has been reported in diabetic patients (1), but the exact pathophysiology of these alterations is still unclear (2). The aims of our study were to characterize the afferent brainstem function by detection of the auditory-evoked potentials in patients with long-standing type 1 diabetes and to analyze possible connections between the central neural dysfunction and the autonomic and peripheral sensory neuropathies.
We enrolled 12 patients with long-standing type 1 diabetes who had normal hearing (age [mean ±SD] 42.1 ±14.8 years, duration of diabetes 23 ±8.9 years, BMI 26.8 ±4.6 kgm2). The quantitative characteristics of the brainstem function were evaluated by the detection of auditory-evoked potentials (3). This procedure consists of the analysis of seven electrical waves generated along the nerve tracts of the auditory system after the delivery of an audible click of short duration via an earphone. The latencies and the interpeak latencies of five waves (I-V) were determined in this study. The presence of cardiovascular autonomic neuropathy was investigated by means of the five standard cardiovascular reflex tests (4), and a score (scale 0–10) was used to express the severity of the overall autonomic disorder (5). Three of these tests (the heart rate response to breathing, the 30/15 ratio, and the Valsalva ratio) evaluate mainly the parasympathetic function, whereas the systolic blood pressure response to standing up and the diastolic pressure change to a sustained handgrip predominantly allow an assessment of the sympathetic integrity. The peripheral sensory nerve function was characterized by evaluation of current perception thresholds (CPTs) with a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD), which permits transcutaneous testing at three sinusoidal frequencies (2 kHz, 250 Hz, and 5 Hz) of electrical stimulus (6). Median and peroneal nerves (digital branches) were studied.
Positive correlations were observed between the autonomic score and the lengths of the latencies of of waves III and V (Table 1). In accordance with this finding, there was a negative relationship between the results of three heart rate tests (the heart rate response to deep breathing, the 30/15 ratio, and the Valsalva ratio) and the prolongation of the latencies of waves III and V. Neither the systolic blood pressure response to standing nor the sustained handgrip test showed any significant correlation with the prolongation of the evoked potentials. Pronounced abnormalities of waves III and V were also recorded during the analysis of the interpeak latencies of the brainstem potentials. Positive correlations were demonstrated between the autonomic score and the interpeak latencies I-III and I-V. The heart rate response to deep breathing and the 30/15 ratio correlated negatively with the interpeak latencies I-III and I-V. These two heart rate tests are considered the most sensitive procedures for autonomic function (4). No significant correlations were found between the other three cardiovascular reflex tests and the interpeak latencies. The higher CPT values obtained at 2,000 and 250 Hz at the peroneal nerve correlated positively with the latencies of waves III (both P < 0.05) and V (both P < 0.01).
As a novel finding, wave III and V latencies were associated with cardiovascular autonomic and peripheral sensory nerve dysfunctions, which are progressive forms of diabetic neuropathy. The parasympathetic nerve dysfunction characterized mainly by the three heart rate tests develops earlier in the course of diabetes. The higher CPT values obtained at 2,000 and 250 Hz indicate large sensory nerve fiber damage, which usually precedes small fiber neuropathy (5). These abnormalities are commonly seen first in the lower extremities. In our study, the impairment of the three heart rate tests and the degree of large sensory nerve dysfunction correlated with the wave III and V latencies. These data may suggest that the abnormalities of waves III and V indicating an impairment of the auditory brainstem function should be regarded as early central manifestations of diabetic neuropathy.
Correlations between cardiovascular reflex tests and latency intervals of auditory-evoked brainstem potentials
| Correlated parameters . | Correlation coefficient . | P . |
|---|---|---|
| Autonomic score and latency of wave III | 0.6149 | <0.05 |
| Heart rate response to breathing and latency of wave III | −0.6450 | <0.001 |
| 30/15 ratio and latency of wave III | −0.5904 | <0.01 |
| Valsalva ratio and latency of wave III | −0.5015 | <0.05 |
| Autonomic score and latency of wave V | 0.4979 | <0.05 |
| Heart rate response to breathing and latency of wave V | −0.4982 | <0.01 |
| 30/15 ratio and latency of wave V | −0.5932 | <0.01 |
| Valsalva ratio and latency of wave V | −0.4802 | <0.05 |
| Autonomic score and interpeak latency I-III | 0.5414 | <0.01 |
| Heart rate response to breathing and interpeak latency I-III | −0.5544 | <0.01 |
| 30/15 ratio and interpeak latency I-III | −0.5111 | <0.05 |
| Autonomic score and interpeak latency I-V | 0.4891 | <0.05 |
| Heart rate response to breathing and interpeak latency I-V | −0.4621 | <0.05 |
| 30/15 ratio and interpeak latency I-V | −0.5434 | <0.05 |
| Correlated parameters . | Correlation coefficient . | P . |
|---|---|---|
| Autonomic score and latency of wave III | 0.6149 | <0.05 |
| Heart rate response to breathing and latency of wave III | −0.6450 | <0.001 |
| 30/15 ratio and latency of wave III | −0.5904 | <0.01 |
| Valsalva ratio and latency of wave III | −0.5015 | <0.05 |
| Autonomic score and latency of wave V | 0.4979 | <0.05 |
| Heart rate response to breathing and latency of wave V | −0.4982 | <0.01 |
| 30/15 ratio and latency of wave V | −0.5932 | <0.01 |
| Valsalva ratio and latency of wave V | −0.4802 | <0.05 |
| Autonomic score and interpeak latency I-III | 0.5414 | <0.01 |
| Heart rate response to breathing and interpeak latency I-III | −0.5544 | <0.01 |
| 30/15 ratio and interpeak latency I-III | −0.5111 | <0.05 |
| Autonomic score and interpeak latency I-V | 0.4891 | <0.05 |
| Heart rate response to breathing and interpeak latency I-V | −0.4621 | <0.05 |
| 30/15 ratio and interpeak latency I-V | −0.5434 | <0.05 |
References
Address correspondence to Dr. Tamás Várkonyi, University of Szeged, 1st Department of Medicine, H-6701, Szeged, P.O. Box 469, Hungary. E-mail: [email protected].
