This study examined the relationship between vestibular function and peripheral measurements of neuropathy in participants with T1D, T2D and healthy controls. Our study found no significant differences in vHIT between participants with T1D, T2D and controls, even after regrouping into different categories based on type of nerve fiber involvement. Despite our sub-grouping of participants with diabetes into groups with and without neuropathy, we were not able to demonstrate any association between vestibular impairment and the presence of peripheral diabetic neuropathy, thus indicating that peripheral neuropathy is not accompanied by impaired nerve function of the VOR.
Relationship between vestibular function and peripheral nerve status
To our knowledge, this is the first study to assess the relationship between the vestibular function and extensive measurements of diabetic peripheral neuropathy in participants with T1D and T2D. Previously, a few studies with divergent results have investigated the relationship between diabetes and the vestibular system. One study compared mean gain values of all SCCs vHIT measurements between three groups: T2D without DPN (
n = 33) with DPN (
n = 33) and controls (
n = 35) and found no significant difference between the groups. The study does not elaborate when a vHIT examination is pathological [
19]. Another study investigated participants with T2D (
n = 25) compared to controls (
n = 25) and did find a significant difference in mean gain values, except the right anterior SCC. There are no mentions of saccades in the study [
33]. Another study examining T1D (
n = 15) and controls (
n = 16) with vHIT had pathological examinations with two patients in all tested SCCs when looking at mean gain values. Saccades are not mentioned in that study. No significant difference between groups was found [
34]. None of these studies investigated both T1D and T2D and the power of each study was limited. Kalkan et al. is in line with our findings regarding the relationship between neuropathic status and vestibular function [
19]. In consideration of the extensive sample size of our study, it could be speculated that our results are more representative of the diabetes population, and that the negative association can truly be trusted.
During our correlation analyses between measurements of neuropathy and vHIT, only total weighted score of COMPASS 31 and right lateral SCC mean gain value showed a weak significant correlation. This in total yielded 1 of 21 correlations to be significant and must be assumed to be a random finding.
A study of T1D (
n = 60) and healthy controls (
n = 20), demonstrated lower gray matter volume in individuals with T1D regardless of DPN and neuropathic pain [
35]. We, however, only found four participants with pathological vHIT examinations with pathological mean gain values and saccades in at least one SCC. There was no association with peripheral alterations. It is, however, interesting that no decrease was found in the T1D group despite the probability of lower gray matter volume. It could be speculated that the findings do not have any clinical significance for the brainstem function except attenuated memory in the cerebrum.
Usage of electroencephalography (EEG) might shed light on central nervous system (CNS) alterations in persons with diabetes, as it records conductivity and velocity of brain waves. As VOR includes a few structures of CNS, EEG might be more susceptible to recording dysfunction. However, to our knowledge no studies have been performed on this matter.
Future studies investigating dynamic postural control could be beneficial in understanding the increased risk of falling [
9].
Strengths
vHIT: pre-training, including vHIT related theory, and collection of data with the ICS Impulse® was done according to updated research supported guidelines and guidance of the primary author [
10]. To ensure quality, consistency, and low degree of interrater variation with testing, the two primary authors of this study exclusively performed all tests. In our analysis of vHIT measurements, we interpret both mean gain values and saccades. It is the opinion of the authors of this article, that mean gain values alone is not sufficient to diagnose hypo functioning VOR with each SCC.
Large nerve fiber assessment: assessing the large nerve fiber can be done in several ways, and the golden standard is electroneurography (ENG). A study investigating the usability of DPNcheck found an excellent correlation in data output when comparing measurements from ENG and DPNcheck and a great interclass correlation. This study therefore concludes that DPNcheck has excellent reproducibility and would be a useful tool in evaluation of DPN [
36]. NPC-stat was used according to the factory manual, and proper use was demonstrated by trained personnel.
Small nerve fiber assessment: QST is a method of testing the small nerve fibers for neuropathy. Studies have shown how the QST have been able to test and detect obvious neurological changes [
37]. The QST was used according to the manual and pre-setting of the software provided, and we were thoroughly educated on the usage of this machinery by trained personnel. To maintain quality and consistency, the thermal plate was placed on the dorsal part of the right foot adjacent to the 2–4 metatarsal.
Autonomic nerve fiber assessment: COMPASS 31 was created as a simple tool for quantifying the severity of autonomic symptoms across several domains. Since the creation of this questionnaire, it has been validated in several studies extensively, demonstrating an association with autonomic function. The questionnaire is originally made in English. To validate the Danish translated version, it was tested on bilingual participants both healthy controls and those with autonomic alterations. It was found that the Danish translation correlated with the English version on all sub scores, and the re-test reliability found no consistent bias [
28].
In our study, we use several well-known and well tested measurements for diabetic neuropathy. By using multiple measurements, we could further assess the extent of neuropathy and correlate the findings with vHIT.
A post-hoc power analysis of this study including the obtained 114 participants yielded 91.4% power. In order to reach 95% power 134 participants were needed.
Limitations
Several limitations must be discussed. First, vHIT: VOR consists of several anatomical structures within the CNS. Therefore, to directly conclude vestibular- or vestibular nerve impairment with vHIT testing, the examiner must make sure that every other structure, involved in the VOR, must function properly. H-configuration and screening of major neurological deficits were, therefore, performed. However, because a complete neurological examination was not performed, other CNS pathologies may have been present and could thereby theoretically have altered the results.
In general, vHIT saccade measurements need interpretation by the examiner, thus increasing the probability of error and interrater variation. Mean gain values are, however, a calculated result recorded by the device and independent of the examiner. By including both the mean gain value and accompanying saccades as mandatory for the classification of hypo functioning VOR, possible weaknesses are limited such as prediction of false pathology.
Evaluating the left anterior and right posterior SCCs an increased number of pathological mean gain values occur persistently. This could be due to systematical error such as right-hand dominance of examiners. Several participants complained about lack of visual fixation of the right eye, when evaluating left anterior and right posterior SCCs, due to the bridge on the frame of the ICS Impulse®. The participants could have suffered from a latent strabismus expressed by the frame. This could have been excluded with a cover-uncover test.
QST: thus reproducibility, it is missing objectivism, and a lot of distractions influence the output [
37].
Some participants were not able to detect change in temperature and only responded to pain regardless of the investigation goal. Some triggered the responder earlier or later than warranted due to both lack of attention and misunderstanding of the information given by the investigator. We did, however, record three consecutive responses per investigation goal, thus eliminating the effect of improper response on the result.
Regarding neuropathic severity, it shows T1D and T2D are more prone to have DPN than controls when looking at large nerve fiber neuropathy.
Within autonomic neuropathy, only a significant difference is seen between T2D and control. It could be speculated that the median age of T1D, being noticeably younger than T2D, influences severity.
In the measurements of small nerve fiber neuropathy, no significant difference is seen at all between the three groups.
Thus, indicating that our included participants might be less affected by the long-term consequences of diabetes and unregulated glucose level, and is therefore not as influenced by DPN in small nerve fibers and autonomic nerve fibers contradicting other studies [
24,
38,
39]. When inspecting our data for vestibular impairment, no significant differences were found, even though Nourizadeh et al. concludes diabetes does affect cochlea [
33]. The study, however, is limited in its power due to a lack of study participants compared to our study.