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ORIGINAL ARTICLE
Year : 2023 | Volume
: 22
| Issue : 1 | Page : 107-111
Brain stem auditory evoked potentials in type 2 diabetes mellitus patients at varying frequencies
Indira Sushil Mishra1, Ranjana Shingne2, Nitu Kumari Roy3
1 Department of Physiology, IGIMS, Patna, Bihar, India
2 Department of Physiology, Dr. Ulhas Patil Medical College and Hospital, Jalgaon, Maharashtra, India
3 Department of Physiology, Rama Medical College and Hospital, Hapur, Uttar Pradesh, India
Correspondence Address:
Indira Sushil Mishra
Department of Physiology, IGIMS, Patna, Bihar
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/aam.aam_13_22
Abstract
Introduction: As per the World Health Organization, in 2005, more than 180 million people had diabetes worldwide. This figure will be more than double by 2030. Neuropathy is common and late complication of diabetes mellitus (DM). Sensory neural hearing loss which is severe at higher frequencies has been reported in Type 2 DM patients. Auditory nerve tract damage increases the latency and reduces the amplitude of the response. Evoked potential recordings evaluate the neural pathways in the central nervous system. Brainstem auditory evoked potentials (BAEP) localize anatomic structures using different waves and detect acoustic and central neuropathy (CN). Hence, brainstem evoked response of audiometry (BERA) is used widely in clinical set up. Aims: Primary: 1. To record BERA waves in normal subjects with normal blood sugar levels (hemoglobin A1C [HbA1C] <5.4. 2. To record BERA waves in Type 2 DM patients. (HbA1C >6.5). Secondary: To study the BERA parameters with the normal subjects with blood sugar subjects and compare them with Type 2 DM patients. Materials and Methods: n = 30, Type 2 DM patients between the age of 35–50 years of either sex were chosen from the Diabetic Clinic of GMC, Aurangabad, Maharashtra. HbA1C test for glycemic control and BERA waves to assess CN were recorded. n = 30 normal subjects with normal blood sugar with age and sex-matched above tests were performed. Statistical Analysis: Unpaired Student's t-test. Results: Mean ± Standard deviation of the absolute latency and interpeak latency of BERA waves at 2, 4, and 6 KHz at 80 dB in Type 2 DM patients were delayed and found to be significant as compared to control group. Conclusion: The above study explains that if BAEP is recorded at higher frequencies like 6 KHz and at 80 dB, CN involvement can be detected earlier in diabetic patients. Hence, it is recommended to carry out BERA in diabetic patients at least once in a year.
Abstract in French Résumé
Introduction: Selon l'Organisation mondiale de la santé, en 2005, plus de 180 millions de personnes étaient atteintes de diabète dans le monde. Cechiffre sera plus 14 que doubler d'ici 2030. La neuropathie est une complication courante et tardive du diabète sucré (DM). Perte auditive neurale sensorielle qui est sévère àdes fréquences plus élevées ont été rapportées chez les patients atteints de diabète de type 2. Les dommages aux voies nerveuses auditives augmentent la latence et réduisent l'amplitude de la réponse. Les enregistrements de potentiels évoqués évaluent les voies neuronales du système nerveux central. Potentiels évoqués auditifs du tronc cérébral (BAEP) 16localiser les structures anatomiques à l'aide de différentes ondes et détecter la neuropathie acoustique et centrale (NC). Par conséquent, le tronc cérébral a évoqué une réponse de 17 L'audiométrie (BERA) est largement utilisée dans les installations cliniques. Objectifs: Primaire : 1. Enregistrer les ondes BERA chez des sujets normaux avec une glycémie normale 18(hémoglobine A1C [HbA1C] <5,4. 2. Pour enregistrer les ondes BERA chez les patients atteints de diabète de type 2. (HbA1C >6,5). Secondaire : Pour étudier le BERA 19 paramètres avec les sujets normaux avec des sujets glycémiques et les comparer avec les patients atteints de diabète de type 2. Matériels et méthodes: n = 30,Des patients atteints de diabète de type 2 âgés de 35 à 50 ans de l'un ou l'autre sexe ont été choisis à la clinique diabétique de GMC, Aurangabad, Maharashtra.Le test HbA1C pour le contrôle glycémique et les ondes BERA pour évaluer la NC ont été enregistrés. n = 30 sujets normaux avec une glycémie normale avec l'âge et 21 appariés selon le sexe ci-dessus ont été effectués. Analyse statistique: test t de Student non apparié. Résultats: moyenne ± écart-type de l'absolu 22 la latence et la latence interpic des ondes BERA à 2, 4 et 6 KHz à 80 dB chez les patients atteints de diabète de type 2 ont été retardées et se sont révélées significatives puisque 23 par rapport au groupe témoin. Conclusion : L'étude ci-dessus explique que si le BAEP est enregistré à des fréquences plus élevées comme 6 KHz et à 80 dB, CN 24l'implication peut être détectée plus tôt chez les patients diabétiques. Par conséquent, il est recommandé d'effectuer BERA chez les patients diabétiques au moins une fois par an
Mots-clés: Latence absolue, potentiels évoqués auditifs du tronc cérébral, réponse évoquée audiométrique du tronc cérébral, neuropathie centrale, 26 latence interpic, diabète sucré de type 2
Keywords: Absolute latency, brain stem auditory evoked potentials, brainstem evoked response of audiometry, central neuropathy, interpeak latency, Type 2 diabetes mellitus
Introduction 
Type-2 diabetes mellitus (DM) patients suffer from hyperglycemia with symptoms of metabolic disorders and neuropathy complications being most frequent.[1] Peripheral polyneuropathy which involves autonomic and peripheral nerves are important complications of DM.[2] Type-2 DM leads to neurologic malfunction and hearing impairment is greater than those without it.[3] The risk of diabetic neuropathy (DN) increases with the increase in duration of diabetes.[4] The hearing loss which is found to be sensory neural, slowly progressive, and bilateral is more severe loss at higher frequencies.[2] Till now, many clinical and diagnostic studies have focused on peripheral and autonomic neural changes in DN but with brain stem evoked response audiometry (BERA), sensory pathways changes in central nervous system (CNS) have been possible. It is a noninvasive electrophysiological tool to identify retro cochlear lesions.[2] The first topographical location of BERA waves I-V from the cochlear nerve, pons, and midbrain was given by Jewett in 1970.[4] This study was done with an aim to study BERA in diabetic patients at 80 dB and at 2KHz, 4KHz, and 6KHz frequencies. An attempt has been made to relate abnormal brain stem auditory evoked potentials (BAEP) with the blood glucose level, CN, and duration of disease. The absolute latencies (AL) and inter-peak latencies were significantly impaired (P < 0.001) in diabetic subjects as compared to control subjects at 2, 4, and 6 KHz frequencies. The incidence of delayed wave latencies was 60%, 70%, and 76.6% at 2 KHz, 4 KHz, and 6 KHz, respectively.[2] It suggests that if BERA is conducted at higher frequency like 6 KHz in diabetic patients, the involvement of central neural axis can be detected earlier.
Materials and Methods The Institutional Ethics Committee approved the study protocol. It was conducted between January 2014 and January 2015 and the study design was cross-sectional comparative type. n = 30, Type 2 DM patients, between the age of 35 and 50 years of either sex or duration of diabetes between 1 and 10 years were chosen from the diabetic clinic of GMC Aurangabad, a tertiary care hospital. n = 30 normal subjects with normal blood sugar subjects were selected as controls. We hypothesized that with the increasing the stimulus of frequencies at 2 KHz, 4 KHz, and 6 KHz and at 80 dB abnormal brainstem auditory evoked potentials BAEP were more common. Rinnes and Webers hearing tests excluded peripheral hearing loss. Pure-tone audiometry was performed on RMS HERMES audiometer machine. Pure-tone thresholds were ranged from 0 to 15 dBHL for frequency 125–8000 Hz. Peripheral neuropathy was excluded by pressure test with blunt object and pricking skin with a pin and pinching muscle tendon for pain test. Proprioceptive tests are sense of position for proximal and distal joints. Subjects were asked to keep the other limb in the same position as rotated and kept in a particular position by the examiner. This test was for large nerve fibers. Tactile localization and tactile two point discrimination tests for touch were done to rule out peripheral neuropathy. Cold and warm test tubes for small fiber nerves for temperature were done.
Group 1 – n = 30, subjects age and sex matched having hemoglobin A1C (HbA1C) below 5.4% were selected as control groupGroup 2 – n = 30, Type 2 DM patients having HbA1C above 6.5% were selected.Exclusion criteria
Patients with a history of ear disease, strokes, cerebrovascular accident, head injury, with overt neuropathy, intake of ototoxic drugs, neurological deficit, occupational history of exposure to prolonged loud noise, family history of deafness, and those with history of drug intake known to cause central neuropathy (CN), e.g., methyldopa, reserpine, phenytoin, antipsychotic, antidepressants, smokers, endocrine disorder, e.g., myxedema, were also excluded from the study.
Age of the subject in complete years was recorded from the medical record department. Body height (Ht) was measured in centimeters by asking the subjects to stand with their heels, buttocks, and head against a wall. A flat object was placed on top of the subject's head, and their Ht was marked on a tape measure affixed to the wall. Body weight in kilograms (kg) was recorded with a standard portable weighing machine. Body mass index (BMI) was calculated as body weight in kilogram divided by square of the body Ht in meters (kg/m2).[5] Overnight fasting venous blood sample was withdrawn before conducting BERA. HbA1C was recorded by A1C Care machine by Card method. Otoscopy and tuning fork tests were performed. Pure-tone audiometry was performed on ARPHI 700 MK audiometer machine. Pure-tone thresholds were ranged from 0 to 15 dBHL for 500–8 KHz.
BAEP were recorded on RMS ALERON 201/401 model in a sound-treated room under standard conditions. Before carrying out the procedure, the patient was made comfortable and relaxed in a sitting position. Skins of the forehead and the mastoid processes were cleaned and made oil free. Objects such as hairpins, hearing aids, jewelries, or other metal objects that might interfere the recordings were asked to be removed. Recording electrodes were cleaned properly and then standard adhesive paste which worked as a conducting medium was applied on them. These electrodes were adhered to their respective cleaned surfaces of patients. Head phone was set on the head of the patients in its required position. Filters were set between 100 Hz and 3000 Hz. A brief click stimulus of very short duration was applied. To confirm the reproducibility of waves 2, recordings were recorded. AL of Waves I, III, V, and Interpeak Latencies (IPL) of Waves I-III, III-V, and I-V were recorded at 80 dB and 2KHz, 4KHz, and 6KHz frequencies. BAEP localizes the lesions in the brainstem as per recorded changes in waves.
Statistical analysis
Statistical analysis was done using GraphPad QuickCalcs online: t-test calculator. The mean values and standard deviation of all the parameters of BERA waves, i.e., AL of Wave I, Wave III, Wave V and IPL of Waves I-III, III-V, and I-V were recorded at varying frequencies of 2, 4, 6 KHz and at 80 dB in the DM patients and control group. Statistical analysis was done using Student's unpaired t-test. P < 0.05 (P < 0.05) was considered statistically significant.
Results n = 30, Group 1 subjects were chosen as control (HbA1C <5.4%) and n = 30, Group 2 Type 2 DM patients were selected (HbA1C >6.5%)
Mean values of Group 1 for the age, weight, Ht, BMI, and HbA1C were 38.26 ± 1.93 years, 60.50 ± 1.23 kg, 1.58 ± 1.01 meter, 24.05 ± 1.21 kg/m2, 5.6 ± 0.01% respectively. The mean values for Group 2 of age, weight, Ht, BMI, and HbA1C were 38.16 ± 1.51 years, 61 ± 1.01 kg, 1.58 ± 1.13 meter, 24.26 ± 1.04 kg/m2, and 10.08 ± 1.15%, respectively [Table 1]The mean values at 2 KHz and 80 dB of Wave I, Wave III, Wave V and IPL I-III, III-V, I-V in Group 1 were 1.59 ± 0.20 (ms), 3.47 ± 0.15 (ms), 5.38 ± 0.17 (ms), 1.73 ± 0.23 (ms), 1.92 ± 0.23 (ms), 3.79 ± 0.34 (ms) and Group 2 were 1.6 ± 0.21 (ms), 3.64 ± 0.15 (ms), 5.71 ± 0.31 (ms), 2.08 ± 0.26 (ms), 2.03 ± 0.18 (ms), 3.99 ± 0.41 (ms), respectively. It was found to be statistically significant except Wave I (P < 0.05) [Table 2]The mean values at 4 KHz and 80 dB of Wave I, Wave III, Wave V and IPL I–III, III–V, I–V in Group 1 were 1.61 ± 0.21 (ms), 3.52 ± 0.17 (ms), 5.44 ± 0.25 (ms), 1.74 ± 0.17 (ms), 1.96 ± 0.28 (ms), 3.80 ± 0.38 (ms) and in Group 2 were 1.70 ± 0.2 (ms), 3.65 ± 0.2 (ms) and 5.80 ± 0.37 (ms), 2.10 ± 0.27 (ms), 2.17 ± 0.21 (ms), 4.07 ± 0.37 (ms), respectively. It was found to be statistically significant except wave I (P < 0.05) [Table 3]Mean values at 6 KHz and 80 dB of Wave I, Wave III and Wave V and IPL of I-III, III-V, I-V in Group 1 were 1.64 ± 0.22 (ms), 3.55 ± 0.16 (ms) and 5.45 ± 0.31 (ms) 1.74 ± 0.17 (ms) 1.97 ± 0.02 (ms) and 3.84 ± 0.37 (ms) and in Group 2 were 1.76 ± 0.22 (ms), 3.68 ± 0.24 (ms) and 5.90 ± 0.25 (ms), 2.20 ± 0.31 (ms), 2.43 ± 0.1 (ms) and 4.17 ± 0.37 (ms), respectively. It was found to be statistically significant (P < 0.05) except Wave I [Table 4]The delayed wave latencies in diabetic patients were 70% (21/30), 76.6% (23/30), and 83.33% (25/30) at 2 KHz, 4 KHz, and 6 KHz, respectively. This suggests earlier detection of central neural axis involvement at higher frequency like 6KHz in diabetic patients by brain stem audiometry evoked response[Table 5] shows relationship between delayed auditory brain stem evoked responses at 2 KHz and duration of illness. At 6 KHz and 80 dB, 35% of diabetic patients with 1–5 years duration of diabetes had delayed auditory brain stem evoked response and those with 6–10 years of duration of diabetes had 93.75% delayed response[Table 6]. At 80 dB and 6 KHz, about 30% diabetic patients with HbA1c between 5.6% and 7% and 70% diabetic with HbA1c >7% had delayed auditory brainstem evoked potential.
Table 2: Absolute latencies and interpeak latencies comparison in Control group and Diabetic Group patients at 2 KHz and 80 db
Table 3: Absolute latencies and interpeak latencies comparison in Control Group and Diabetic Group patients at 4 KHz and 80 db
Table 4: Absolute latencies and inter peak latencies comparison in Control Group and Diabetic Group patients at 6 KHz and 80 dB
Table 5: Relationship between auditory brainstem evoked potential and duration of illness in diabetic patients at 6 KHz and 80 dB
Table 6: Relationship between auditory brainstem evoked potential and hemoglobin A1C (%) in diabetic patients at 80 dB and 6 KHz Discussion In this study, BAEPs were recorded in Type 2 diabetic patients and were compared with the control group. The latency of Wave I was found to be equal. Hence, 8th nerve transmission till cochlear nucleus was found to be normal.
At 2 KHz, a highly significant delay in absolute latency (AL) of Wave III and a significant delay in Wave V were found. Sharma R et al. supported above results.[2] Verma et al. study did not support it.[6] A highly significant delay in inter-peak latency of I-III while a significant delay in inter-peak latency III-V and I-V were found. Virtaniemi had similar result.[7]
At 4KHz, a highly significant delay in AL of Waves III and V and IPL of Wave I–III and I– V while a significant delay in IPL III-V has been found. Sharma et al. reported similar result [Graph 1].[2]
At 6 KHz, a highly significant (P < 0.001) delay in AL of Waves III and V and IPL of Waves I-III, III-V, and I– V were found. Sharma et al. supported the above findings [Graph 1].[2]
The percentage of diabetic subjects at 2 KHz, 4 KHz, and 6 KHz with delayed AL of Waves III and V and IPL I-III, III-V and I-V were 70% (21/30), 76.6% (23/30), and 83.33% (25/30), respectively. As the frequency of stimulus was increased from 2 KHz, 4 KHz to 6 KHz, delayed brainstem evoked potentials were recorded easily. This is supported by Axelsson and Fagerberg[8] and Sharma et al. study.[2] Significant delay in the AL of Waves III and V and IPL of I– III, III– V, and I– V in Type 2 diabetic DM patients indicates derangement in the auditory pathway at brainstem and midbrain. At higher frequency, i.e., at 6 KHz diabetic patients had normal pure tone audiogram and no hearing-related complaint. Hence, subclinical involvement as well as severity can be detected early by BERA test at 6 KHz. Study done by Sharma et al. had similar findings.[2]
At 6 KHz and 80 dB, 35% of diabetic patients with 1–5-year duration of diabetes had delayed auditory brain stem evoked response and those with 6–10 years of duration of diabetes had 93.75% delayed response [Table 5]. This is supported by the study where patients with short-term diabetes had normal hearing and those with long-duration diabetes, significant hearing impairment at higher frequencies (4–8 KHz), were reported.[9] As per Jorgensen and Buch, (1961) microangiopathy leads to diabetic neuropathy which is responsible for its long-term complication. The above study concludes that duration of illness may be one of the risk factors for CN in the DM patients.[10]
At 80 dB and 6 KHz, about 30% diabetic patients with HbA1c between 5.6% and 7% and 70% diabetic with HbA1c >7% had delayed auditory brainstem evoked potential [Table 6] and [Graph 2]. The above results are similar with Pozzessere et al. where abnormal evoked potentials were found related to glycemic control.[9],[11] Reske Neilson and Makishima and Tanaka reported CN due to brain tissue degeneration and spiral ganglion atrophy in diabetic patients.[12]
Summary and Conclusion If BERA is carried out at higher frequency like 6 KHz and 80 dB in diabetic patients, central neuronal axis involvement can be detected earlier. Long duration of diabetes and deranged glycemic control are also risk factors for CN. Hence, this study recommends BERA test to be made mandatory for all the diabetic patients on a regular basis at least once in a year to reduce the morbidity in diabetic patients.
Ethics approval and Consent to participate and publish
Ethical approval and consent to participate and publish were taken.
Financial support and sponsorship
All the expenditures were borne by the author Dr. Mishra Indira Sushil.
Conflicts of interest
There are no conflicts of interest.
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