Impairment of the central nervous system is a frequent complication of diabetes (1), but its clinical importance is still underestimated. The exact pathophysiology of the central nervous dysfunction is not clear, but it seems to be multifactorial, involving vascular and metabolic factors, similar to the pathogenesis of diabetic peripheral neuropathy (1). Earlier studies revealed new data on the central manifestations of diabetes but did not permit a comprehensive comparative analysis of the peripheral and central neuronal dysfunctions (2,3).
We recently observed significant correlations between the impairment of the auditory evoked potentials and the severity of autonomic and peripheral sensory neuropathy in type 1 diabetes (4). In addition to the detection of the auditory evoked potentials, evaluation of the visual evoked potentials furnishes another diagnostic tool for the assessment of functional anomalies of the cerebral function, even at an early stage of the pathogenetic process (2). The aim of this study was to demonstrate the possible associations between the latencies of visual evoked potentials and the severity of the cardiovascular autonomic and peripheral sensory dysfunctions in type 1 diabetes.
In the study, 12 middle-aged patients with longstanding type 1 diabetes were enrolled, 5 males and 7 females with a mean (±SD) age of 46.3 ± 14.9 years, a mean duration of diabetes of 24.1 ± 9.4 years, and a mean BMI of 27 ± 4.1 kg/m2. Patients with proliferative retinopathy, impaired visual acuity, or neuronal dysfunction of nondiabetic origin were excluded from the study.
The visual evoked potentials were recorded from an active electrode placed over the occipital region, with a reference electrode at the left ear (5). Monocular, pattern-reversal checkboard stimulation was used with a frequency of 1.8 Hz. Two measurements were performed for both eyes, and the visual function was evaluated via the latency of the major positive component of the potentials P100. The five standard cardiovascular reflex tests were applied to assess autonomic function (6). Heart rate tests (the heart rate response to deep breathing, the 30:15 ratio, and the Valsalva ratio) mainly reflect the parasympathethic function, while evaluation of the systolic blood pressure responses to standing and the diastolic pressure changes in response to a sustained handgrip primarily allow the assessment of sympathetic integrity. The results of each of the five tests were scored as 0 (normal), 1 (borderline), or 2 (abnormal). A final score was calculated (range 0–10) to express the severity of the overall autonomic disorder. The peripheral sensory nerve function was characterized by evaluation of the current perception thresholds (CPTs), with a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD), which permits transcutaneous testing (7) at three sinusoidal frequencies of electrical stimulus (2 kHz, 250 Hz, and 5 Hz). Median and peroneal nerves (digital branches) were studied. Significant positive correlations were found between the autonomic score and the lengths of the latencies of the P100 waves of the right and left eyes (Table 1). Further analyses revealed a negative relationship between the results of the three heart rate tests (the heart rate response to deep breathing, the 30:15 ratio, and the Valsalva ratio) and the prolongation of the P100 latencies for both eyes. The systolic blood pressure response to both standing and sustained handgrip test did not display any significant correlation with the abnormal latencies of the P100 potentials. The impaired sensory nerve function manifested in high CPT values at stimulation frequencies 2,000, 250, and 5 Hz, which reflects hypesthesia at the peroneal nerve, correlated positively with the P100 latencies of the right and left eyes. The CPT values of the median nerve did not correlate with the abnormal central visual function.
The parasympathetic nerve dysfunction, characterized mainly by means of heart rate tests, develops earlier in the course of diabetes (6), and sensory neuropathy affects the lower limbs predominantly. The impairment of visual pathways is considered an early sign among the electrophysiological visual function alterations (8). It is still unclear as to whether there are similarities between the altered central and peripheral neuronal manifestations of diabetic neuropathy. In our study, the prolongation of the P100 latencies of the visually evoked potentials for both eyes was associated with parasympathetic autonomic neuropathy and the hypesthetic form of lower-limb sensory neuropathy. These data are consistent with our previous findings from an assessment of the autonomic and the sensory neuropathy and auditory brainstem function in patients with type 1 diabetes, and may suggest that an impairment of visual evoked potentials should be regarded as an early central manifestation of diabetic neuropathy.
Correlations between neuropathy parameters and P100 latency intervals of visual evoked potentials
| Correlated parameters . | Correlation coefficient . | P . |
|---|---|---|
| Right eyes | ||
| Autonomic score and P100 latency | 0.6042 | <0.01 |
| Heart rate response to breathing and P100 latency | −0.4359 | <0.05 |
| Valsalva ratio and P100 latency | −0.5464 | <0.01 |
| 30:15 ratio and P100 latency | −0.4523 | <0.05 |
| CPT at 2,000 Hz on peroneal nerve and P100 latency | 0.5021 | <0.05 |
| CPT at 250 Hz on peroneal nerve and P100 latency | 0.5627 | <0.01 |
| CPT at 5 Hz on peroneal nerve and P100 latency | 0.5819 | <0.01 |
| Left eyes | ||
| Autonomic score and P100 latency | 0.5721 | <0.01 |
| Heart rate response to breathing and P100 latency | −0.4617 | <0.05 |
| Valsalva ratio and P100 latency | −0.5456 | <0.01 |
| 30:15 ratio and P100 latency | −0.5948 | <0.01 |
| CPT at 2,000 Hz on peroneal nerve and P100 latency | 0.6246 | <0.01 |
| CPT at 250 Hz on peroneal nerve and P100 latency | 0.6715 | <0.001 |
| CPT at 5 Hz on peroneal nerve and P100 latency | 0.7056 | <0.001 |
| Correlated parameters . | Correlation coefficient . | P . |
|---|---|---|
| Right eyes | ||
| Autonomic score and P100 latency | 0.6042 | <0.01 |
| Heart rate response to breathing and P100 latency | −0.4359 | <0.05 |
| Valsalva ratio and P100 latency | −0.5464 | <0.01 |
| 30:15 ratio and P100 latency | −0.4523 | <0.05 |
| CPT at 2,000 Hz on peroneal nerve and P100 latency | 0.5021 | <0.05 |
| CPT at 250 Hz on peroneal nerve and P100 latency | 0.5627 | <0.01 |
| CPT at 5 Hz on peroneal nerve and P100 latency | 0.5819 | <0.01 |
| Left eyes | ||
| Autonomic score and P100 latency | 0.5721 | <0.01 |
| Heart rate response to breathing and P100 latency | −0.4617 | <0.05 |
| Valsalva ratio and P100 latency | −0.5456 | <0.01 |
| 30:15 ratio and P100 latency | −0.5948 | <0.01 |
| CPT at 2,000 Hz on peroneal nerve and P100 latency | 0.6246 | <0.01 |
| CPT at 250 Hz on peroneal nerve and P100 latency | 0.6715 | <0.001 |
| CPT at 5 Hz on peroneal nerve and P100 latency | 0.7056 | <0.001 |
References
Address correspondence to Dr. Tamás Várkonyi, University of Szeged, 1st Dept. of Medicine, H-6701, Szeged, P.O. Box 469, Hungary. E-mail: [email protected].
